<p>Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats</p>

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

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Hypermethylation of EFEMP1 in the Hippocampus May Be Related to the Deficit in Spatial Memory of Rat Neonates Triggered by Repeated Administration of Propofol

BioMed Research International ◽

10.1155/2020/8851480 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Nu Zhang ◽

Zhiyi Liao ◽

Pinwen Wu ◽

Hao Fang ◽

Guoping Cai

Keyword(s):

Learning And Memory ◽

Spatial Learning ◽

Cognitive Functions ◽

Promoter Region ◽

Matrix Protein ◽

Repeated Administration ◽

Neonatal Rat ◽

Extracellular Matrix Protein ◽

Spatial Learning And Memory ◽

Neonatal Rats

It has been confirmed that repeated application of propofol, as an intravenous and short-fast-acting anesthetic, in neonatal animals or humans may produce long-term deficits in cognitive functions. With the aim of explaining the neurotoxic effects of repeated administration of propofol on neonatal rat pups from P7 to P9 especially from an epigenetic perspective, the present study used the Morris water maze to detect cognitive deficits in spatial learning and memory, Sequenom methylation on the CpG island located in the promoter region of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to assess the methylation level of this region, and Western blot to measure the expression of EFEMP1, TIMP-3, and MMP-9. As the results have shown, repeated propofol administration on neonatal rats caused significant systemic growth retardation, impairment of spatial learning and memory, and hypermethylation of the CpG sites in the promoter region of EFEMP1 accompanied by lower expression of EFEMP1 and TIMP-3 and enhanced expression of MMP-9. These data suggest that repeated propofol administration in neonatal rats may generate hypermethylation in the promoter region of EFEMP1 which results in downregulation of the expression of EFEMP1 and tissue inhibitor of metalloproteinase-3 (TIMP-3) but upregulation of the expression of matrix metalloproteinase-9 (MMP-9), which together may affect the stability of ECM to hamper the development of the central nervous system and therefore lead to deficits in cognitive functions.

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