Journal
MOLECULAR NEUROBIOLOGY
Volume 60, Issue 4, Pages 1766-1781Publisher
SPRINGER
DOI: 10.1007/s12035-022-03174-x
Keywords
Ischemia stroke; Perception; Emotion; Chemogenetics; CREB; BDNF
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Cerebral ischemia leads to excitotoxicity and neural apoptosis. In this study, the effects of chemogenetic inhibition or activation of glutamatergic neurons in the vCA1 region on sequelae induced by cerebral ischemia were investigated. The results showed that inhibition of vCA1 pyramidal neurons alleviated neurological deficits, pain perception, anxiety, and depression, while activation had limited effects. Additionally, overexpression of CREB protein in vCA1 pyramidal neurons improved the dysfunction induced by ischemic stroke by upregulating BDNF.
Cerebral ischemia is characterized by several pathological reaction evolving over time. Hyperactivation of glutamatergic neurons is the main factor leading to excitotoxicity which potentiates oxidative stress and triggers the mechanisms of neural apoptosis after cerebral ischemia. However, it is unclear whether glutamate in the ventral hippocampal Cornus Ammonis 1 (vCA1) acts a part in neurological deficits, pain perception, anxiety, and depression induced by ischemic stroke. We investigated the effects of chemogenetic inhibition or activation of vCA1 pyramidal neurons which are mainly glutamatergic neurons on sequelae induced by cerebral ischemia. Our results revealed that inhibition of vCA1 pyramidal neurons by chemogenetics alleviated neurological deficits, pain perception, anxiety, and depression caused by cerebral ischemia in mice, but activation of vCA1 pyramidal neurons had limited effects. Moreover, we found that stroke was accompanied by decreased levels of cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in vCA1, which are modulated by glutamate. In this study, overexpression of CREB protein in pyramidal neurons in vCA1 by AAV virus significantly upregulated the content of BDNF and ameliorated the dysfunction induced by ischemic stroke. Our results demonstrated activation of the CREB-BDNF pathway in vCA1 pyramidal neurons significantly improved neurological deficits, pain perception, anxiety, and depression induced by ischemic stroke.
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