a(MESH:"Cholinergic Neurons")
It is clear that AD involves loss of cholinergic neurons in the brain as well as an overall reduction in nAChRs, and it seems that different subunits are differentially up- or down-regulated in AD in different brain regions and different cell types. PubMed:19293145
Loss of cholinergic neurons has often been demonstrated as lowered ChAT activity in brains of patients with AD. Early post mortem studies indicated a loss of ChAT activity restricted to the neocortex (Slotkin et al., 1990) and this has been confirmed in more recent studies on frontal lobe and temporal cortex (Lai et al., 2006). It is noteworthy that an increase in ChAT activity in the surviving neurons was interpreted as a possible compensatory mechanism (Slotkin et al., 1990). PubMed:19293145
AD involves loss of cholinergic cells not only in the cortex but also in subcortical nuclei. Up to 50% loss of neurons and of ChAT activity has been reported at autopsy in the locus ceruleus of brains from patients with AD compared with brains from subjects without AD, whereas no change was observed for adrenergic brainstem nuclei (Strong et al., 1991). PubMed:19293145
1 Several lines of evidence suggest that impaired cholinergic signaling plays a key role in mediating both the cognitive and the behavioral impairments observed in AD patients.12 The basal forebrain cholinergic system is disproportionately affected in AD patients, with a robust loss of cholinergic neurons, including those innervating the hippocampus and cortex. PubMed:24511233
Furthermore, it has also been proposed that the nerve growth factor (NGF) has the potential to preserve cholinergic neurons PubMed:26813123
Moreover, previous studies have shown that treatment with NGF can counteract cholinergic atrophy and memory deficits in aged rats 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
Interestingly, M1 receptor signaling affects several of AD major hallmarks, including cholinergic deficit, cognitive dysfunction, and tau and Aβ pathologies PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder afflicting millions of people. It is diagnosed by the progressive loss of cognitive function and behavioral defi cits and is characterized by the presence of neurofibrillary tangles (NFTs), senile plaques, cholinergic neuron loss, and neuronal atrophy at autopsy PubMed:24590577
The third important hallmark of AD is cholinergic hypofunction. The neurotransmitter acetylcholine (ACh) exerts its physiological functions by activating either ionotropic nicotinic ACh receptors (nAChRs) or metabotropic muscarinic ACh receptors (mAChRs). It has been reported that in AD brains there are (1) reduced choline acetyltransferase levels accompanied by decreased ACh synthesis; (2) significant loss of cholinergic neurons; (3) reduction in the numbers of postsynaptic neurons accessible to ACh; (4) cholinergic neuronal and axonal abnormalities; and (5) reduction in nAChR levels PubMed:24590577
4OH-GTS-21 had no effect on cholinergic cell size in the unlesioned sides of the septa of the wild type or PS1 mice, but did cause atrophy of these neurons in the APP/PS1 mice PubMed:17640819
4OH-GTS-21 had no effect on cholinergic cell size in the unlesioned sides of the septa of the wild type or PS1 mice, but did cause atrophy of these neurons in the APP/PS1 mice PubMed:17640819
As a result, the proaggregant lines showed a range of defects including paralysis, axonal degeneration of GABAergic and cholinergic motor neurons, presynaptic defects, synapse loss, and mitochondrial transport defects early in adulthood PubMed:29191965
Comparison of the cellular distribution of NF-κB in the nucleus basalis of Meynert of AD and control patients showed that the proportion of large cholinergic neurons with elevated nuclear p65 was significantly increased in AD, suggesting an association between NF–κB functions and the process of cholinergic degeneration PubMed:25652642
Loss of cholinergic neurons has often been demonstrated as lowered ChAT activity in brains of patients with AD. Early post mortem studies indicated a loss of ChAT activity restricted to the neocortex (Slotkin et al., 1990) and this has been confirmed in more recent studies on frontal lobe and temporal cortex (Lai et al., 2006). It is noteworthy that an increase in ChAT activity in the surviving neurons was interpreted as a possible compensatory mechanism (Slotkin et al., 1990). PubMed:19293145
Experimental data using non-human primates and rodents have demonstrated that injuries introduced to basal forebrain cholinergic neurons that innervate the cortex lead to attention deficit PubMed:26813123
All these cholinergic alterations that take place in AD closely correlates with impaired attention and memory observed in 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
All these cholinergic alterations that take place in AD closely correlates with impaired attention and memory observed in patients PubMed:26813123
It has been demonstrated that stimulation of cholinergic neurons in precise regions of the brainstem can promote REM (rapid eye movement) sleep, dose-dependently PubMed:26813123
ACh synthesis takes place in the cytoplasm of cholinergic neurons PubMed:26813123
Although cholinergic neurons can synthesize choline, the de novo synthesis contributes only with a very small fraction of the total choline that is needed for ACh synthesis (see Fig. 1) PubMed:26813123
Cholinergic neurons secrete AChE into the synaptic cleft, where the enzyme is normally associated with the plasma membrane (see Fig. 1) PubMed:26813123
It has been postulated that the loss of cholinergic neurons and the consequent impairment in dopaminergic transmission could be the main factors underling AD-related psychiatric symptoms PubMed:26813123
It has been postulated that the loss of cholinergic neurons and the consequent impairment in dopaminergic transmission could be the main factors underling AD-related psychiatric symptoms PubMed:26813123
It has been postulated that the loss of cholinergic neurons and the consequent impairment in dopaminergic transmission could be the main factors underling AD-related psychiatric symptoms PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123
Interestingly, M1 receptor signaling affects several of AD major hallmarks, including cholinergic deficit, cognitive dysfunction, and tau and Aβ pathologies PubMed:26813123
The neurotransmitter acetylcholine (ACh) is synthesised, stored and released by cholinergic neurons, and exerts its effects on the central nervous system (CNS) and peripheral nervous system (PNS) through two distinct types of receptor: the muscarinic and nicotinic ACh receptors (mAChRs and nAChRs). PubMed:28901280
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