1. Catalog
  2. Citations
  3. PubMed:26010758

PubMed: 26010758

Title
Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD.
Journal
PloS one
Volume
10
Issue
None
Pages
e0128224
Date
2015-01-01
Authors
Ait-Ghezala G | Beaulieu-Abdelahad D | Crawford F | Li R | Mullan M | Paris D | Verma M

Evidence e166f1ce29
JSON

Transgenic mouse models of AD overexpressing Aβ peptides generally show greater locomotor activity and disinhibition in the elevated plus maze compared to non-transgenic mice, suggest- ing hyperactivity and a lower level of anxiety [28–30].

a(CHEBI:"amyloid-beta") increases bp(GO:locomotion) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta") decreases path(MESH:Anxiety) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence f22c4e2847
JSON

Unlike wild-type mice, Tg PS1/APPswe mice elicited social interaction deficits and spent an equal amount of time in the chamber containing the empty cage or the chamber containing the unfamiliar (Stranger 1) mouse (Fig 4A). Anatabine at a dosage of 20mg/Kg/Day restored sociability in Tg PS1/APPswe mice as Tg PS1/APPswe mice treated with anatabine spent significantly more time in the chamber containing the unfamiliar mouse (Stranger 1) and less time in the chamber containing the empty cage (Fig 4B).

a(CHEBI:"amyloid-beta") decreases path(MESH:"Interpersonal Relations") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:Anatabine) increases path(MESH:"Interpersonal Relations") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence a21607117c
JSON

A significant increase in Iba-1 bur- den was observed in the cortex and hippocampus of Tg PS1/APPswe mice compared to their control wild-type littermates, suggesting increased Iba-1 immunopositive microglia in the brain of Tg PS1/APPswe mice (Fig 5A).

a(CHEBI:"amyloid-beta") increases p(HGNC:AIF1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

bp(GO:"microglial cell activation") positiveCorrelation p(HGNC:AIF1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

p(HGNC:AIF1) positiveCorrelation bp(GO:"microglial cell activation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence 5ad65d3355
JSON

A significant increase in CD45 immunopositive microglia/macrophage was observed in the cortex of Tg PS1/APPswe mice compared to wild- type mice (CD45 immunonegative) (Fig 5C).

a(CHEBI:"amyloid-beta") increases p(HGNC:PTPRC) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Cell Ontology (CL)
microglial cell
MeSH
Cerebral Cortex
MeSH
Alzheimer Disease

Evidence 7677a8bb97
JSON

We ob- served an elevation of STAT3 phosphorylation in the hippocampus and cortex of Tg PS1/ APPswe compared to their control wild-type littermates (Fig 6A).

a(CHEBI:"amyloid-beta") increases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence 042d028d58
JSON

We also observed elevation of NFκB activation in the vicinity of Aβ deposits in the brain of Tg PS1/APPswe mice (Fig 7A).

a(CHEBI:"amyloid-beta") increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 93cb2d8f25
JSON

Additionally, we found that Bace1 mRNA expression is significantly increased in the brain of Tg PS1/APPswe mice compared to wild- type littermates, whereas a significant reduction in Bace1 mRNA levels is observed in Tg PS1/ APPswe receiving 20 mg/Kg/Day of anatabine in their drinking water showing that at this dosage anatabine can mitigate the upregulation of Bace1 expression in Tg PS1/APPswe mice (Fig 9).

a(CHEBI:"amyloid-beta") increases r(HGNC:BACE1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

a(CHEBI:Anatabine) decreases r(HGNC:BACE1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence c8aad7a7d3
JSON

We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy.

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:

a(CHEBI:Anatabine) decreases path(MESH:Gliosis) View Subject | View Object

Appears in Networks:

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Tauopathies

Evidence 866d5dbfbf
JSON

We have shown previously that anatabine displays some anti-inflammatory properties by reducing the activation of NFκB and STAT3 [17,18].

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:Anatabine) decreases act(p(HGNC:STAT3)) View Subject | View Object

Appears in Networks:

Evidence 11363d0eb0
JSON

We have previously shown that anatabine inhibits STAT3 and NFκB activation [18] resulting in decreased neuroinflammation in a mouse model of multiple sclerosis.

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Multiple Sclerosis

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Multiple Sclerosis

a(CHEBI:Anatabine) decreases act(p(HGNC:STAT3)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Multiple Sclerosis

Evidence c97b57354f
JSON

Anatabine has a chemical structure closely related to nicotine and is a full agonist of α7 and α4β2 nicotinic acetylcholine receptors (nAChR) but is a more potent α7 nAChR agonist than nicotine [15,16].

a(CHEBI:Anatabine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:

Evidence e95c8dd031
JSON

Interestingly, we found a significant reduction in the expression of amyloid plaque associated phospho-p65 NFκB immunopositive cells in Tg PS1/APPswe mice treated with anatabine at either 10 or 20 mg/Kg/Day (Fig 7B) showing that anatabine prevents NFκB activation in the brain of Tg PS1/APPswe mice.

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

a(CHEBI:Anatabine) decreases p(FPLX:NFkappaB, pmod(Ph, Ser, 536)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 90e65661c5
JSON

A significant reduction in STAT3 phosphorylation was observed in the hippocampus and cortex of Tg PS1/APPswe mice treated with 10 or 20 mg/Kg/Day of anatabine compared to Tg PS1/APPswe receiving regular drinking water (Fig 6B) showing that anatabine prevents STAT3 activation in the brain of Tg PS1/APPswe mice.

a(CHEBI:Anatabine) decreases act(p(HGNC:STAT3)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence 8af6e727bf
JSON

Interestingly, the hyper- active behavior of Tg PS1/APPswe mice was suppressed with the anatabine treatment at a dos- age of 20 mg/Kg/Day (Fig 2B and 2C).

a(CHEBI:Anatabine) decreases bp(GO:locomotion) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 151908b8d0
JSON

The disinhibition affecting Tg PS1/APPswe mice was suppressed following treatment with anatabine at a dosage of either 10 or 20 mg/Kg/Day at both the time points (Figs 2D and 3D).

a(CHEBI:Anatabine) increases path(MESH:Anxiety) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 801193da99
JSON

Interestingly, Tg PS1/APPswe mice treated with anata- bine at a dosage of 20 mg/Kg/Day, but not 10mg/Kg/day showed a significant reduction in Iba- 1 burden in the hippocampus compared to untreated Tg PS1/APPswe mice (Fig 5A and 5B), suggesting that anatabine suppresses microgliosis in the brain of Tg PS1/APPswe mice.

a(CHEBI:Anatabine) decreases p(HGNC:AIF1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(CHEBI:Anatabine) decreases bp(GO:"microglial cell activation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence ab6718e7c7
JSON

However, we observed a significant reduction in CD45 immunopositive microglia/macrophage in Tg PS1/APPswe mice receiving anatabine at a dosage of 10 and 20 mg/Kg/Day compared to Tg PS1/APPswe mice receiving regular drink- ing water (Fig 5C and 5D).

a(CHEBI:Anatabine) decreases p(HGNC:PTPRC) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Cell Ontology (CL)
microglial cell
MeSH
Cerebral Cortex
MeSH
Alzheimer Disease

Evidence 9f1defd42a
JSON

We observed that anatabine reduces brain Aβ burden both in the cortex and the hippocampus of Tg PS1/APPswe mice using immunostaining with the antibody 4G8 which recognizes Aβ (Fig 8A and 8B).

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence a00d659071
JSON

We found a significant reduction in Cox-2 mRNA expression in Tg PS1/ APPswe mice treated with anatabine at a dosage of 20 mg/Kg/Day (Fig 10).

a(CHEBI:Anatabine) decreases r(HGNC:PTGS2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence c04f662513
JSON

A dose dependent suppression of iNOS transcription was observed in Tg PS1/APPswe mice treated with anata- bine at a dosage of 10 or 20 mg/Kg/Day compared to untreated Tg PS1/APPswe mice (Fig 10).

a(CHEBI:Anatabine) decreases r(HGNC:NOS2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.