bp(GO:memory)
Similar impairments in spatial learning and memory were observed in mice that had undergone lymphatic ligation (Extended Data Fig. 5g–j), supporting the notion that the observed effect is a result of dysfunctional meningeal lymphatic drainage and not an artefact of the ablation method using visudyne PubMed:30046111
Significant transcriptional alterations were also associated with excitatory synaptic remodelling and plasticity, hippocampal neuronal transmission, learning and memory and ageing-related cognitive decline (Extended Data Fig. 5q, r) PubMed:30046111
It was also demonstrated that fibril-free AβO solutions are essential for memory loss (Brito-Moreira et al. 2017), while the fibrillar Aβ in amyloid deposits is not the active factor affecting the cognition (Martins et al. 2008). PubMed:29196815
It was also demonstrated that fibril-free AβO solutions are essential for memory loss (Brito-Moreira et al. 2017), while the fibrillar Aβ in amyloid deposits is not the active factor affecting the cognition (Martins et al. 2008). PubMed:29196815
It was also shown that soluble AβOs may directly trigger dysfunction of neural signaling, which leads to early memory loss and the progression of dementia in AD. PubMed:29196815
In normal rats, impaired memory of a learned behavior was observed after intraventricular application of soluble oligomers of Aβ42 isolated directly from human AD brains (Shankar et al. 2008). Furthermore, AβO injections resulted in reduction of a synapse number and their function in dose-dependent manner. It also led to the inhibition of LTP and enhancement of long-term synaptic depression (LTD) in rodent hippocampus (Shankar et al. 2008). PubMed:29196815
Although excessive Abeta causes synaptic dysfunction and synapse loss [142], low levels of Abeta increase hippocampal longterm potentiation and enhances memory, indicating a novel positive, modulatory role on neurotransmission and memory [158,159] PubMed:21214928
BACE1 deficiency in AD model mice have been shown to rescue cholinergic dysfunction, neuronal loss and memory deficits, correlating with a dramatic reduction in Abeta40/42 levels [79-81] PubMed:21214928
In vivo studies have also shown that sAPP-alpha promotes learning and memory in animal models (Meziane et al. 1998; Taylor et al. 2008) PubMed:22122372
The loss of nAChR subunits, as determined by [3H]- epibatidine binding, seems to take place after the transition from mild cognitive impairment (MCI) to AD (Sabbagh et al., 2006), although the loss of epibatidine binding did not correlate with decline in memory, cognitive performance, or with the development of neurofibrillary tangles or plaques (Sabbagh et al., 2001). PubMed:19293145
Which pathway is activated by Abeta depends upon the time of exposure to the amyloid peptide: chronic applications of oligomeric Abeta to hippocampal slice cultures activate the JNK/MAPK pathway but inhibit the ERK/MAPK pathway, whereas short-term applications of Abeta oligomers do not activate JNK (Bell et al., 2004). This may be one of the routes whereby Abeta impairs memory, because ERK-1 and ERK-2 play key roles in the signaling events central to memory (Satoh et al., 2007). PubMed:19293145
Alzheimer’s disease (AD) is the most common form of dementia in elderly persons. It is a neurodegenerative disease marked by decline in memory and cognitive performance, including deterioration of language as well as defects in visual and motor coordination, and eventual death (for review, see Cummings, 2004). PubMed:19293145
Additionally, recent studies demonstrated that BQCA was effective in reversing memory deficits in Y-maze object recognition and spontaneous alternation tasks in rats.71,72 PubMed:24511233
The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233
M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233
In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233
The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233
M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233
M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233
Conversely, the most commonly associated symptoms of AD are cognitive in nature and include deficits in learning and memory. However, 50%–80% of AD patients display psychotic and behavioral disturbances that are correlated with poor social and functional outcomes PubMed:24511233
For example, local infusion of the α7 antagonist, methyllycaconitine (MLA), or the β2∗ antagonist, dihydro-β-erythroidine (DHβE), into the basolateral amygdala, the ventral hippocampus, or the dorsal hippocampus impairs the working memory of rats seeking food reward within a 16-arm radial maze (146–148). PubMed:17009926
In general, nicotinic agonists improve certain forms of memory, and nicotinic antagonists and cholinergic lesions impair memory (5, 141–145). PubMed:17009926
In animal studies, acute and chronic nicotine administration improves working memory, and nicotinic agonists were found to improve learning and memory in humans and nonhuman primates (145). PubMed:17009926
In general, nicotinic agonists improve certain forms of memory, and nicotinic antagonists and cholinergic lesions impair memory (5, 141–145). PubMed:17009926
In animal studies, acute and chronic nicotine administration improves working memory, and nicotinic agonists were found to improve learning and memory in humans and nonhuman primates (145). PubMed:17009926
For example, local infusion of the α7 antagonist, methyllycaconitine (MLA), or the β2∗ antagonist, dihydro-β-erythroidine (DHβE), into the basolateral amygdala, the ventral hippocampus, or the dorsal hippocampus impairs the working memory of rats seeking food reward within a 16-arm radial maze (146–148). PubMed:17009926
By modulating activity-dependent events, nAChRs participate in fundamental aspects of synaptic plasticity that are involved in attention, learning, memory, and development (3, 12–16). PubMed:17009926
Moreover, published data indicate that ACh is involved in memory PubMed:26813123
Further studies have demonstrated that endogenous acetylcholine is important for modulation of acquisition [17], encoding [18], consolidation [19], reconsolidation [20], extinction [21] and retrieval of memory PubMed:26813123
It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123
Moreover, it has been shown that blocking CA3 cholinergic receptors impairs the encoding of information and memory PubMed:26813123
In a large-scale placebo-controlled clinical trial, it was demonstrated that xanomeline, a muscarinic agonist with reasonable selectivity for M1/M4 receptors, exhibits a positive effect in minimizing, in a dose-dependent manner, cognitive and psychiatric symptoms in AD, including memory deficit, mood disturbance, agitation and hallucinations PubMed:26813123
The importance of the cholinergic neurons from the nucleus basalis of Meynert on memory is highlighted by the fact that the specific degeneration of these neurons takes place in Alzheimer’s disease (AD) and contributes to the memory loss exhibited by AD patients PubMed:26813123
All these cholinergic alterations that take place in AD closely correlates with impaired attention and memory observed in patients PubMed:26813123
Moreover, previous studies have shown that treatment with NGF can counteract cholinergic atrophy and memory deficits in aged rats PubMed:26813123
For example, it has been shown that the benzyl quinolone carboxylic acid (BQCA), which is an M1-selective allosteric agonist, is effective in increasing spontaneous excitatory postsynaptic currents in the medial prefrontal cortex (mPFC) pyramidal cells and improving memory in a transgenic mouse model of AD PubMed:26813123
The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information PubMed:26813123
The importance of the cholinergic neurons from the nucleus basalis of Meynert on memory is highlighted by the fact that the specific degeneration of these neurons takes place in Alzheimer’s disease (AD) and contributes to the memory loss exhibited by AD patients PubMed:26813123
In fact, the memory deficit and neuropathology severity observed in patients exhibiting AD highly correlate with changes in hippocampal synaptic transmission, especially with changes in synaptophysin expression, a presynaptic vesicle protein PubMed:26813123
In fact, the memory deficit and neuropathology severity observed in patients exhibiting AD highly correlate with changes in hippocampal synaptic transmission, especially with changes in synaptophysin expression, a presynaptic vesicle protein PubMed:26813123
One example is xanomeline, an mAChR agonist with selectivity for the M1 and M4 subtypes. Xanomeline improves working memory in rodents and improves cognition and reduces psychotic episodes in AD patients, but it failed during phase-II clinical trial because of serious side-effects, probably due to simultaneous activation of M1 and M4 mAChRs (M4 > M1) PubMed:24590577
Cotinine is a nicotine metabolite known for its positive effects on memory and attention and lower toxicity compared to nicotine (Hatsukami et al., 1997) PubMed:25514383
Chronic treatment with AF267B reduces Abeta plaques and tau hyperphosphorylation and rescues learning and memory impairments in 3×Tg AD mice PubMed:24590577
In mice with scopolamine-induced deficits, PQCA, a selective M1 mAChR positive allosteric modulator[87], improves not only recognition memory, spatial working memory, and executive function, but also blood-flow in the frontal cortex, though the mechanism is not yet clear. PubMed:24590577
Members of the mAChR family are widely expressed in various regions in the central nervous system (CNS) and in the peripheral system. They play crucial roles in diverse physiological processes such as memory, attention, nociception, motor control, sleep-wake cycles, and cardiovascular, renal, and gastrointestinal functions PubMed:24590577
Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577
An in vivo Abeta infusion in mice was able to enhance hippocampal dependent memory, highlighted with memory tasks such as the Morris water maze and contextual fear conditioning, which are both hippocampus dependent behavioural tasks (Puzzo et al.,2008) PubMed:25514383
Nicotine treatment improved the memory deficit, highlighted with the Morris water maze task. Surprisingly, this study showed a dose dependent increase of alpha7 nAChR, a result that is in contrast with the literature (Oddo et al., 2005) PubMed:25514383
In a study conducted by Zhi et al. (2014), this molecule was used to treat a mouse model obtained with injections of the peptide Aß25-35. Administration for 11 days of SV improved memory performance in the Morris water maze task and promoted survival of CA1 pyramidal cells. This effect was proposed to be promoted by alpha7 nAChRs, since it is blocked by MLA administration (Zhi et al., 2014) PubMed:25514383
In a study conducted by Zhi et al. (2014), this molecule was used to treat a mouse model obtained with injections of the peptide Aß25-35. Administration for 11 days of SV improved memory performance in the Morris water maze task and promoted survival of CA1 pyramidal cells. This effect was proposed to be promoted by alpha7 nAChRs, since it is blocked by MLA administration (Zhi et al., 2014) PubMed:25514383
Significantly, a 4-month treatment of Tg2576 mice with GW3965 reduced plaque deposition by > 50% and improved contextual memory in these animals [13]. PubMed:21718217
Treatment of 5-month-old APP/PS1 mice for 8 weeks with ATRA (20 mg/kg/day) resulted in significant decreases in Ab deposition and tau phosphorylation in these mice. Additionally, it attenuated memory deficits seen in the Morris water maze [77]. PubMed:21718217
In this study, pioglitazone treatment was shown to improve memory and cognition in these patients [67,68]. PubMed:21718217
A Phase II clinical trial in which patients were treated with rosiglitazone for 6 months showed improvements in attention and memory retention, but only in patients who did not have an APOE4 allele. PubMed:21718217
A different result was reported by Vanmierlo et al. who found that LXR agonist treatment resulted in restoration of memory, but did not find a change in plaque burden [48]. PubMed:21718217
A very recent study also reported memory defects in mice lacking NACHO/TMEM35 done by scientists unaware of NACHO’s role in controlling nAChRs (Kennedy et al., 2016) PubMed:28445721
In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009) PubMed:21482353
As a consequence of nAChR hypersensitivity, lynx1 knockout mice display increased levels of Ca2+ in neurons, enhancements in synaptic efficacy, and improved learning and memory functions (Miwa et al., 2006; Darvas et al., 2009; Tekinay et al., 2009) PubMed:21482353
Interestingly enough, a considerable body of evidence exists to suggest that the nAChRs are involved in cognitive and memory functions (Levin 2000; Newhouse and Kelton 2000; Newhouse et al 1997; Sahakian and Coull 1994) PubMed:11230871
The potential therapeutic benefit of nAChR stimulation in AD is based upon the fact that nicotine improves memory in animals, healthy subjects, and AD patients (Levin 2000; Newhouse and Kelton 2000; Newhouse et al 1997; Rusted and Warburton 1992) PubMed:11230871
Acute administration of nicotine to AD patients has resulted in a measurable short-term improvement in learning, memory, and attentional performance (Jones et al 1992) PubMed:11230871
Recently, the nicotinic agonist ABT- 418 improved verbal learning and memory on a selective reminding task in AD patients (Potter et al 1999) PubMed:11230871
Two partial agonists of alpha7 nAChRs, GTS-21 (also a strong alpha4beta2 antagonist) and MeM-3454 (also a strong 5-hydroxytryptamine type 3 receptor (5HT3) antagonist)149 (TABLe 1), further showed a procognitive action and, in preclinical studies, MeM-3454 enhanced episodic, spatial and working memory. PubMed:19721446
initially evaluated in normal subjects, GTS-21 was found to significantly improve attention and memory. in a second Phase i trial187, GTS-21 normalized P50 auditory gating in patients with schizophrenia. PubMed:19721446
As expected, AR-R17779 — a selective partial alpha7 nAChR agonist — improved scopolamine-elicited deficits in social recognition, and the 24-hour memory retention interval in unimpaired animals. Repeated doses of AR-R17779 enhanced long-term learning and attenuated working-memory deficits in rats. PubMed:19721446
Amyloid plaques form in the entorhinal cortex of patients with Alzheimer’s disease and this region, which connects the neocortex and the hippocampus, plays a crucial part in memory. it has been suggested that plaques in this region represent the lytic remnants of degenerated, Abeta1–42-burdened pyramidal neurons, and that amyloid internalization depends on alpha7 nAChR mediated Ca2+ entry162. Of interest, chronic nicotine treatment has been shown to reduce the plaque burden in animal models of Alzheimer’s disease123. PubMed:19721446
First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446
First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446
By contrast, deleting the alpha7 nAChR subunit in a mouse model of Alzheimer’s disease that overexpresses a mutated form of the human amyloid precursor protein confers protection against memory loss and synaptic dysfunction, supporting a crucial role for alpha7 nAChR as a target288. PubMed:19721446
One of the salient events at early stages of this disease (usually pre- clinical) is the impairment in hippocampus-based episodic memory which can be improved by enhancement of cholinergic transmission [191]. PubMed:22040696
One of the salient events at early stages of this disease (usually pre- clinical) is the impairment in hippocampus-based episodic memory which can be improved by enhancement of cholinergic transmission [191]. PubMed:22040696
The less cytotoxic analogue of geldanamycin, 17-AAG, has improved brain penetrance. It decreased Aβ levels 223 , improved memory 224 and lowered tau in transgenic AD mice 224 . 17-AAG also reduced α-synuclein oligomers in H4 cells 220 . PubMed:30116051
Interestingly, the UPS is important for elimination of tau and other neurotoxic proteins in post synaptic dendritic compartments (a key site of spreading), where it plays a more general role favouring synaptic plasticity, den- dritogenesis and memory formation 49,52 . PubMed:30116051
Further, mice injected with tau oligomers in the proximity of the hippocampus experienced immediate memory impairment (Lasagna-Reeves et al., 2011) PubMed:28420982
CyP40 was recently shown to disaggregate tau fibrils in vitro and prevents toxic tau accumulation in vivo preserving memory, demonstrating a neuroprotective role for CyP40 in the brain (Baker et al., 2017). PubMed:29311797
Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. PubMed:28775333
RGFP966, a selective HDAC3 inhibitor, has been shown to affect sensory cortical plasticity and memory formation (Bieszczad et al., 2015). PubMed:28771976
These results clearly indicated that MPT0G211 can penetrate the BBB, where it potentially ameliorates learning and memory deficits. PubMed:29844403
Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a memory-associated protein.Transgenic mice expressing human tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ) exhibit AD-related memory deficits and impaired hippocampal long-term potentiation (LTP). TauKQ reduces synaptic KIBRA levels and disrupts activity-induced postsynaptic actin remodeling and AMPA receptor insertion. The LTP deficit was rescued by promoting actin polymerization or by KIBRA expression. In AD patients with dementia, we found enhanced tau acetylation is linked to loss of KIBRA. PubMed:27041503
Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. PubMed:28775333
Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to increase the level of many antioxidants, including glutathione-S transferase (GST), and is negatively regulated by the activity of GSK-3β. Our results indicated the increased nuclear localization of Nrf2 and level of GST, suggesting the increased activity of the transcription factor as a result of GSK-3β suppression, consistent with the decreased oxidative stress observed. Consistent with the improved learning and memory, and consistent with GSK-3b being a tau kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8 mice compared to that of RAO-treated SAMP8 mice. PubMed:24355211
SIRT1 activation or elevation ameliorates pathology and neurodegeneration in AD (Qin et al., 2006; Kim et al., 2007). Loss of SIRT1 induces impairment of learning and memory (Gao et al., 2010; Michán et al., 2010). PubMed:29540553
In 25-month-old mice, the number of errors and the latency in the learning phase negatively correlated with the Sumo3 level in the dorsal hippocampus. PubMed:21843595
Deficiency of the NLRP3 gene reduces Aβ deposition and plays a protective role on memory and behavior (Heneka et al.,2013) PubMed:24561250
Further experiments based on the injection of a PP2A inhibitor in the rat hippocampus demon- strated tau hyper-phosphorylation, and learning and memory deficits [49, 50]. PubMed:22299660
This inhibition of Aβ secretion during macroautophagy deficiency results in aberrant cytosolic accumulation of Aβ, which ultimately evokes neurodegeneration accompanied with memory loss. PubMed:29758300
Moreover, administration of UCH-L1 can reverse the amyloid b-protein–induced synaptic dysfunction and memory loss in transgenic mice overexpressing APP and PS1 (Gong et al. 2006). PubMed:22908190
Soluble Ab oligomers inhibit hippocampal long-term potentiation and alter memory and learning performance PubMed:22908190
Stimulating lysosomal proteolytic efficiency in the TgCRND8 APP mouse model by deleting an endogenous inhibitor of lysosomal cysteine proteases (cystatin B) rescues lysosomal pathology, eliminates abnormal autolysosomal accumulation of autophagy substrates, including Ab, decreases Ab and amyloid deposition, and ameliorates learning and memory deficits (Yang et al. 2011) PubMed:22908190
The UPS is also critically involved in learning and memory. PubMed:22908190
Although key to the survival of all cells, endocytosis supports unique neuronal functions, including aspects of synaptic transmission and plasticity underlying memory and learning. PubMed:22908190
Indeed, transgenic mice expressing UBB+1 have an impaired UPS and show contextual memory deficits in both water maze and fear conditioning paradigms, without specific neuropathological findings (Fischer et al. 2009). PubMed:22908190
Conversely, deletion of the neuronal rab5 GEF, rin1, reduces rab5 activation, increases LTP induction in the amygdala, and enhances fear learning and memory, most likely by increasing surface levels of AMPA receptors (Dhaka et al. 2003). PubMed:22908190
Moreover, administration of UCH-L1 can reverse the amyloid b-protein–induced synaptic dysfunction and memory loss in transgenic mice overexpressing APP and PS1 (Gong et al. 2006). PubMed:22908190
Recently, extracellular tau oligomers were shown to impair long term potentiation (LTP) and memory [40]. PubMed:28528849
TauRDΔK comprises the structural elements required for the pathologic assembly of tau filaments, and it causes reversible memory deficits and synapse loss in regulatable transgenic mice [11,25]. PubMed:28528849
Remarkably, in two regulatable transgenic mouse models expressing human tau with the P301L mutation (rTg4510) or expressing the repeat domain of tau with the ΔK280 mutation, switching off tau expression improved memory impairment even though NFTs remained, clearly showing that tau aggregates are not sufficient for neurodegeneration and the cognitive effects that are typically observed in these models PubMed:26631930
Remarkably, in two regulatable transgenic mouse models expressing human tau with the P301L mutation (rTg4510) or expressing the repeat domain of tau with the ΔK280 mutation, switching off tau expression improved memory impairment even though NFTs remained, clearly showing that tau aggregates are not sufficient for neurodegeneration and the cognitive effects that are typically observed in these models PubMed:26631930
The molecular mechanisms underlying the aforementioned involvement of NF-κB proteins in learning and memory have not been completely comprehended, although recent evidence has implicated NF-κB – induced transcriptional activation of Protein Kinase A (PKA) catalytic subunit that culminates in activation of CREB (cyclic AMP-response element binding protein) signaling [77] which is regarded as the molecular switch that converts short-term memory to long-term memory PubMed:28745240
It considerably decreased A 1-42-stimulated memory disorders in mice [128]. PubMed:29179999
Memory defi-ciencies were improved by -tocopherol in transgenic mice. PubMed:29179999
It improved ICV A 1-42-activated spatial learning, and memory deficiencies were ameliorated via the interference of NF-B signaling and the inhibition of inflammatory cytokines [155]. PubMed:29179999
Beneficial effects of 4-O-methylhonokinol on memory were observed by the reduction of Aaggregation in A 1-42-injected mice and memory-impaired mice with its anti-oxidative and anti-inflammatory qualities [141–143]. PubMed:29179999
Ginsenoside Rd showed neuro-protective effects with A 40 activated impairments in rat brains [225] and ameliorated learning and memory capability in APP transgenic mice, via reducing the activity of NF-B [226]. PubMed:29179999
Paeoniflorin improved memory impairments and lowered A accumulation in APP/PS1 trans-genic mice [1]. PubMed:29179999
It ameliorated spatial learning and memory disorder, which was caused by A 1-42 and was associated with the inter-ference of NF-B activity and the inhibition of IL-1 and TNF-expression [183]. PubMed:29179999
AGEs induce tau hyperphosphorylation, memory deterioration, decline of synaptic proteins, and impairment of long-term potentiation in rats [10]. PubMed:27288790
We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381
We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381
Adnp+/− mice compared with Adnp+/+ mice spent significantly shorter time periods in exploring the new objects, indicative of impaired memory, with intranasal NAP-CB treatment completely ameliorating this impairment (Fig. 2a, b). PubMed:30664622
Adnp+/− mice compared with Adnp+/+ mice spent significantly shorter time periods in exploring the new objects, indicative of impaired memory, with intranasal NAP-CB treatment completely ameliorating this impairment (Fig. 2a, b). PubMed:30664622
Adnp+/− mice compared with Adnp+/+ mice spent significantly shorter time periods in exploring the new objects, indicative of impaired memory, with intranasal NAP-CB treatment completely ameliorating this impairment (Fig. 2a, b). PubMed:30664622
Which pathway is activated by Abeta depends upon the time of exposure to the amyloid peptide: chronic applications of oligomeric Abeta to hippocampal slice cultures activate the JNK/MAPK pathway but inhibit the ERK/MAPK pathway, whereas short-term applications of Abeta oligomers do not activate JNK (Bell et al., 2004). This may be one of the routes whereby Abeta impairs memory, because ERK-1 and ERK-2 play key roles in the signaling events central to memory (Satoh et al., 2007). PubMed:19293145
M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233
Conversely, the most commonly associated symptoms of AD are cognitive in nature and include deficits in learning and memory. However, 50%–80% of AD patients display psychotic and behavioral disturbances that are correlated with poor social and functional outcomes PubMed:24511233
The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233
M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233
The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233
M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233
In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233
By modulating activity-dependent events, nAChRs participate in fundamental aspects of synaptic plasticity that are involved in attention, learning, memory, and development (3, 12–16). PubMed:17009926
The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information PubMed:26813123
Moreover, published data indicate that ACh is involved in memory PubMed:26813123
It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123
The importance of the cholinergic neurons from the nucleus basalis of Meynert on memory is highlighted by the fact that the specific degeneration of these neurons takes place in Alzheimer’s disease (AD) and contributes to the memory loss exhibited by AD patients PubMed:26813123
The importance of the cholinergic neurons from the nucleus basalis of Meynert on memory is highlighted by the fact that the specific degeneration of these neurons takes place in Alzheimer’s disease (AD) and contributes to the memory loss exhibited by AD patients PubMed:26813123
In fact, the memory deficit and neuropathology severity observed in patients exhibiting AD highly correlate with changes in hippocampal synaptic transmission, especially with changes in synaptophysin expression, a presynaptic vesicle protein PubMed:26813123
In fact, the memory deficit and neuropathology severity observed in patients exhibiting AD highly correlate with changes in hippocampal synaptic transmission, especially with changes in synaptophysin expression, a presynaptic vesicle protein PubMed:26813123
Members of the mAChR family are widely expressed in various regions in the central nervous system (CNS) and in the peripheral system. They play crucial roles in diverse physiological processes such as memory, attention, nociception, motor control, sleep-wake cycles, and cardiovascular, renal, and gastrointestinal functions PubMed:24590577
Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577
In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009) PubMed:21482353
Interestingly enough, a considerable body of evidence exists to suggest that the nAChRs are involved in cognitive and memory functions (Levin 2000; Newhouse and Kelton 2000; Newhouse et al 1997; Sahakian and Coull 1994) PubMed:11230871
First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446
First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446
Amyloid plaques form in the entorhinal cortex of patients with Alzheimer’s disease and this region, which connects the neocortex and the hippocampus, plays a crucial part in memory. it has been suggested that plaques in this region represent the lytic remnants of degenerated, Abeta1–42-burdened pyramidal neurons, and that amyloid internalization depends on alpha7 nAChR mediated Ca2+ entry162. Of interest, chronic nicotine treatment has been shown to reduce the plaque burden in animal models of Alzheimer’s disease123. PubMed:19721446
Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. PubMed:28775333
Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. PubMed:28775333
Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to increase the level of many antioxidants, including glutathione-S transferase (GST), and is negatively regulated by the activity of GSK-3β. Our results indicated the increased nuclear localization of Nrf2 and level of GST, suggesting the increased activity of the transcription factor as a result of GSK-3β suppression, consistent with the decreased oxidative stress observed. Consistent with the improved learning and memory, and consistent with GSK-3b being a tau kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8 mice compared to that of RAO-treated SAMP8 mice. PubMed:24355211
Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a memory-associated protein.Transgenic mice expressing human tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ) exhibit AD-related memory deficits and impaired hippocampal long-term potentiation (LTP). TauKQ reduces synaptic KIBRA levels and disrupts activity-induced postsynaptic actin remodeling and AMPA receptor insertion. The LTP deficit was rescued by promoting actin polymerization or by KIBRA expression. In AD patients with dementia, we found enhanced tau acetylation is linked to loss of KIBRA. PubMed:27041503
SIRT1 activation or elevation ameliorates pathology and neurodegeneration in AD (Qin et al., 2006; Kim et al., 2007). Loss of SIRT1 induces impairment of learning and memory (Gao et al., 2010; Michán et al., 2010). PubMed:29540553
RGFP966, a selective HDAC3 inhibitor, has been shown to affect sensory cortical plasticity and memory formation (Bieszczad et al., 2015). PubMed:28771976
In 25-month-old mice, the number of errors and the latency in the learning phase negatively correlated with the Sumo3 level in the dorsal hippocampus. PubMed:21843595
The UPS is also critically involved in learning and memory. PubMed:22908190
We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381
We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.