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  3. DOI:10.4172/2168-975X.1000126

DOI: 10.4172/2168-975X.1000126

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Evidence 8ca90dc7f4
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During the time course of the treatment (40 days), 25% of Tg Tau P301S placebo mice became paralyzed (3 out of 12) whereas none (0 out of 11) in the anatabine treatment group developed paralysis during the study duration (Figure 1)

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

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Evidence 046ab31664
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Approximately 44 % (4 out of 9 non-paralyzed mice) of the placebo group (33 week-old mice) elicited an abnormal hind-limb extension reflex when suspended by the tail compared to 18% (2 out of 11) of Tg Tau P301S mice treated with anatabine (Figure 1).

a(CHEBI:Anatabine) increases bp(GO:"motor behavior") View Subject | View Object

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Evidence c82824d3fa
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In addition, Tg Tau P301S mice treated with anatabine showed an increased latency to fall (T-test, P<0.05) from an accelerating rotarod apparatus compared to Tg Tau P301S mice receiving regular drinking water (Figure 2) showing improved motor coordination.

a(CHEBI:Anatabine) increases bp(GO:"motor behavior") View Subject | View Object

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Evidence b12cc32df9
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Tg Tau P301S mice treated with anatabine spent significantly more time (T-test, P<0.05) in the open arms of the elevated plus maze than placebo Tg Tau P301S mice (Figure 3).

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

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Evidence 4aa4335616
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Compared to age matched wild-type mice, 32 week-old Tg Tau P301S mice did not show spatial learning impairment in the RAWM (data not shown)

a(CHEBI:Anatabine) increases path(MESH:"Spatial Learning") View Subject | View Object

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Evidence ea569c9259
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No effect of the anatabine treatment was observed on tau expression (T-test, P>0.05) in Tg Tau P301S mice (Figure 4).

a(CHEBI:Anatabine) causesNoChange p(HGNC:MAPT) View Subject | View Object

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MeSH
Brain
MeSH
Spinal Cord

Evidence 7c7f4ec3fd
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In both the detergent soluble and insoluble fractions of the brain and spinal cord homogenates of Tg Tau P301S mice, we found that tau phosphorylation was significantly reduced (T-tests, P<0.05) by the anatabine treatment for all the AD phosphorylated epitopes tested (Figure 6)

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 396), pmod(Ph, Ser, 404)) View Subject | View Object

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Annotations
MeSH
Brain
MeSH
Spinal Cord

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

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Annotations
MeSH
Brain
MeSH
Spinal Cord

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

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Annotations
MeSH
Brain
MeSH
Spinal Cord

Evidence e08398fe16
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Moreover, a significant reduction in MC1-immunoreactivity (P<0.05) was observed in the detergent soluble and insoluble fractions of brain and spinal cord homogenates from Tg Tau P301S mice treated with anatabine showing that anatabine prevents the formation of pathological tau conformers (Figure 7).

a(CHEBI:Anatabine) decreases a(GO:"neurofibrillary tangle") View Subject | View Object

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MeSH
Brain
MeSH
Spinal Cord

Evidence 8af714afbe
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Additionally, a significant reduction (P<0.05) in tau oligomers levels (TOC1 immunopositive) was detected both in the brain and the spinal cord of Tg Tau P301S treated with anatabine using dot-blots (Figure 8).

a(CHEBI:Anatabine) decreases a(HBP:"Tau oligomers") View Subject | View Object

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MeSH
Brain
MeSH
Spinal Cord

Evidence 50707007c4
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We observed that anatabine significantly prevented the formation of MC1-positive tau oligomers (Figure 9) by western-blots in both the brain and the spinal cord of Tg Tau P301S mice (T-tests, P<0.05) further confirming the data obtained with the dot-blots

a(CHEBI:Anatabine) decreases a(HBP:"Tau oligomers") View Subject | View Object

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Annotations
MeSH
Brain
MeSH
Spinal Cord

Evidence 9e82dd00bb
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A significant reduction in Iba1 immunoreactivity was observed both in the brain (T-test, P<0.01) and spinal cord (T-test, P<0.01) homogenates of Tg Tau P301S mice treated with anatabine. Figure 10.

a(CHEBI:Anatabine) decreases bp(HBP:Microgliosis) View Subject | View Object

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MeSH
Brain
MeSH
Spinal Cord

Evidence 232f690be9
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We found a significant increase in brain AKT Ser473 phosphorylation (T-test, P<0.001) and GSK3β Ser9 phosphorylation (T-test, P<0.001) in Tg Tau P301S mice treated with anatabine. Figure 11.

a(CHEBI:Anatabine) increases p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

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Annotations
MeSH
Brain

a(CHEBI:Anatabine) increases p(FPLX:AKT, pmod(Ph, Ser, 473)) View Subject | View Object

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Annotations
MeSH
Brain

Evidence b552627ff7
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GSK3β is inactivated upon phosphorylation of Ser9 by protein kinase B (AKT) [41] whereas AKT phosphorylation at Ser473 results in AKT activation [42].

p(FPLX:AKT) directlyIncreases p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

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p(FPLX:AKT, pmod(Ph, Ser, 473)) increases act(p(FPLX:AKT)) View Subject | View Object

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p(HGNC:GSK3B, pmod(Ph, Ser, 9)) decreases act(p(HGNC:GSK3B)) View Subject | View Object

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Evidence bb8e25f00c
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Glycogen synthase 3β (GSK3β) is one of the main serine-threonine kinase responsible for tau phosphorylation and has been shown to affect tau phosphorylation at multiple AD relevant epitopes including Ser396, Ser404, Thr231 and Ser202

p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

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p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 404)) View Subject | View Object

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p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

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p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

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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.