Ligustrazine Attenuates Hyperhomocysteinemia-induced Alzheimer-like Pathologies in Rats

Ligustrazine,an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort,has been clinically applied to treat the cerebrovascular diseases.Hyperhomocystcincmia(Hhcy)is an independent risk factor for Alzheimer's disease(AD).Memory deficits can be caused by Hhcy via pathologies of Aβ-like tau and amyloid-β(Aβ)in the hippocampus.Here,we investigated whether homocysteine(Hey)can induce Aβ-like pathologies and the effects of ligustrazine on these pathologies.The Hey rat model was constructed by 14-day Hey injection via vena caudalis,and rats were treated with daily intragastric administration of ligustrazine at the same time.We found that the pathologies of tau and Aβ were induced by Hey in the hippocampus,while the Hcy-induced tau hyperphosphorylation and Aβ accumulation could be markedly attenuated by simultaneous ligustrazine treatment.Our data demonstrate that ligustrazine may be used as a promising neuroprotective agent to treat the Hcy-induced Aβ-like pathologies.

Hydrogen sulfide enhances adult neurogenesis in a mouse model of Parkinson's disease

Hydrogen sulfide(H_2S) is regarded to be a protectant against diseases of the central nervous system and cardiovascular system.However, the mechanism by which H_2S elicits neuroprotective effects in the progression of Parkinson's disease(PD) remains unclear.To investigate the role of H_2S in delaying the pathological process of PD, we used the most common sodium hydrosulfide(Na HS) as an H_2S donor and established a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid(MPTP/p) in the present study.Our results show that H_2S reduced neuronal loss during the progression of PD.Notably, we found that H_2S exhibited protective effects on dopaminergic neurons.Excitingly, H_2S also increased the proliferation of neural stem cells in the subventricular zone.Next, we evaluated whether the neuroprotective effects of H_2S on dopaminergic neurons in PD are dependent on adult nerve regeneration by treating primary adult neural stem cells cultured ex vivo with 1-methyl-4-phenylpyridine.Our results show that H_2S could prevent nerve injury induced by 1-methyl-4-phenylpyridine, promote the growth of neurospheres, and promote neurogenesis by regulating Akt/glycogen synthase kinase-3β/β-catenin pathways in adult neural stem cells.These findings confirm that H_2S can increase neurogenesis in an adult mouse model of PD by regulating the Akt/glycogen synthase kinase-3β/β-catenin signaling pathway.This study was approved by the Animal Care and Use Committee of Nanjing Medical University, China(IACUC Approval No.1601153-3).