DOI: 10.4172/2168-975X.1000126


Evidence 8ca90dc7f4

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)

Evidence 046ab31664

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).

Evidence c82824d3fa

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.

Evidence b12cc32df9

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).

Evidence 4aa4335616

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)

Evidence ea569c9259

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

Evidence 7c7f4ec3fd

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)

Evidence e08398fe16

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).

Evidence 8af714afbe

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).

Evidence 50707007c4

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

Evidence 9e82dd00bb

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.

Evidence 232f690be9

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.

Evidence b552627ff7

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

Evidence bb8e25f00c

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


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