Dataset Information

Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice.

ABSTRACT:

Objective

The purpose of this study was to investigate the effect of methamphetamine (MA) on spatial learning and memory and the role of tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.

Methods

Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase (ERK) in the mouse prefrontal cortex (PFC) and hippocampus.

Results

Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA+THP-treated mice than in MA-treated mice.

Conclusion

Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.

SUBMITTER: Chen YJ

PROVIDER: S-EPMC5560324 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice.

Chen Yan-Jiong YJ Liu Yan-Ling YL Zhong Qing Q Yu Yan-Fang YF Su Hong-Liang HL Toque Haroldo A HA Dang Yong-Hui YH Chen Feng F Xu Ming M Chen Teng T

Neuroscience bulletin 20120601 3

<h4>Objective</h4>The purpose of this study was to investigate the effect of methamphetamine (MA) on spatial learning and memory and the role of tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.<h4>Methods</h4>Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used ...[more]

PMID: 22622821

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Project description:Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota. However, the role and mechanism of the gut microbiota in cognitive impairment after METH exposure are still largely unknown. Here, we investigated the impact of the gut microbiota on the phenotype status of microglia (microglial phenotypes M1 and microglial M2) and their secreting factors, the subsequent hippocampal neural processes, and the resulting influence on spatial learning and memory of chronically METH-exposed mice. We determined that gut microbiota perturbation triggered the transformation of microglial M2 to M1 and a subsequent change of pro-brain-derived neurotrophic factor (proBDNF)-p75NTR-mature BDNF (mBDNF)-TrkB signaling, which caused reduction of hippocampal neurogenesis and synaptic plasticity-related proteins (SYN, PSD95, and MAP2) and, consequently, deteriorated spatial learning and memory. More specifically, we found that Clostridia, Bacteroides, Lactobacillus, and Muribaculaceae might dramatically affect the homeostasis of microglial M1/M2 phenotypes and eventually contribute to spatial learning and memory decline after chronic METH exposure. Finally, we found that fecal microbial transplantation could protect against spatial learning and memory decline by restoring the microglial M1/M2 phenotype status and the subsequent proBDNF-p75NTR/mBDNF-TrkB signaling in the hippocampi of chronically METH-exposed mice. IMPORTANCE Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated "specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment" pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.

Dataset Information

Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice.

Objective

Methods

Results

Conclusion

Publications

Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice.

Similar Datasets

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