Memantine improves cognitive deficits by activiating NGF/TrkA signaling in APP/PS1 transgenic mice / 中国药理学通报

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

EGCG ameliorating learning and memory impairment in APP/PS1 mice by inhibiting p75 NTR pathway / 中国药理学通报

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.