Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain

Adult neurogenesis is a flexible process that depends on the environment and correlates with cognitive functions. Cognitive functions are impaired by various factors including space flight conditions and reduced physical activity. Physically active life significantly improves both cognition and the hippocampal neurogenesis. Here, we analyzed how 3-day simulated microgravity caused by hindlimb unloading (HU) or dynamic foot stimulation (DFS) during HU can affect the hippocampal neurogenesis. Adult Wistar rats were recruited in the experiments. The results demonstrated a decrease in the number of doublecortine (DCX) positive neural progenitors, but proliferation in the subgranular zone of the dentate gyrus was not changed after 3-day HU. Analysis of the effects of DFS showed restoration of neural progenitor population in the subgranular zone of the dentate gyrus. Additionally, we analyzed activity of the cRaf/ERK1/2 pathway, which is one of the major players in the regulation of neuronal differentiation. The results demonstrated inhibition of cRaf/ERK1/2 signaling in the hippocampus of HU rats. In DFS rats, no changes in the activity of cRaf/ERK1/2 were observed. Thus, we demonstrated that the process of neurogenesis fading during HU begins with inhibition of the formation of immature neurons and associated ERK1/2 signaling activity, while DFS prevents the development of mentioned alterations.

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Alpinia oxyphylla Miq. and Its Active Compound P-Coumaric Acid Promote Brain-Derived Neurotrophic Factor Signaling for Inducing Hippocampal Neurogenesis and Improving Post-cerebral Ischemic Spatial Cognitive Functions

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.577790 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yacong He ◽

Shuang Chen ◽

Bun Tsoi ◽

Shuhua Qi ◽

Bing Gu ◽

...

Keyword(s):

Signaling Pathway ◽

Spatial Learning ◽

Cognitive Functions ◽

Akt Signaling ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Coumaric Acid ◽

Akt Signaling Pathway

Alpinia oxyphylla Miq. (AOM) is a medicinal herb for improving cognitive functions in traditional Chinese medicine for poststroke treatment, but its efficacies and underlying mechanisms remain unknown. In the present study, we tested the hypothesis that AOM could induce adult hippocampal neurogenesis and improve poststroke cognitive impairment via inducing brain-derived neurotrophic factor (BDNF) signaling pathway. In order to test the hypothesis, we performed both in vivo rat experiments using transient middle cerebral artery occlusion (MCAO) model and in vitro neural stem cell (NSC) experiments using oxygen–glucose deprivation plus reoxygenation. First, AOM treatment significantly up-regulated the expression of BDNF, tropomycin receptor kinase B (TrkB), and phosphorylated AKT (p-AKT) in the hippocampus, enhanced adult hippocampal neurogenesis, and improved the spatial learning/memory and cognitive functions in the post-MCAO ischemic rats in vivo. Next, in vitro studies confirmed p-coumaric acid (P-CA) to be the most effective compound identified from AOM extract with the properties of activating BDNF/TrkB/AKT signaling pathway and promoting NSC proliferation. Cotreatment of BDNF/TrkB-specific inhibitor ANA12 abolished the effects of P-CA on inducing BDNF/TrkB/AKT activation and the NSC proliferation. Finally, animal experiments showed that P-CA treatment enhanced the neuronal proliferation and differentiation in the hippocampus, improved spatial learning and memory functions, and reduced anxiety in the transient MCAO ischemic rats. In conclusion, P-CA is a representative compound from AOM for its bioactivities of activating BDNF/TrkB/AKT signaling pathway, promoting hippocampal neurogenesis, improving cognitive functions, and reducing anxiety in post–ischemic stroke rats.

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