Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus

Jiuyang Ding; Jian Huang; Xiang Tang; Lingyi Shen; Shanshan Hu; Jiaojiao He; Ting Liu; Zhixing Yu; Yubo Liu; Qiyan Wang; Jiawen Wang; Na Zhao; Xiaolan Qi; Jiang Huang

doi:10.3389/fncel.2022.1003617

Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus

Front Cell Neurosci. 2022 Nov 2:16:1003617. doi: 10.3389/fncel.2022.1003617. eCollection 2022.

Authors

Jiuyang Ding^{1

2}, Jian Huang³, Xiang Tang^{4

5

6

7

8}, Lingyi Shen⁹, Shanshan Hu¹⁰, Jiaojiao He¹¹, Ting Liu¹², Zhixing Yu¹, Yubo Liu¹, Qiyan Wang¹, Jiawen Wang¹, Na Zhao¹, Xiaolan Qi², Jiang Huang¹

Affiliations

¹ School of Forensic Medicine, Guizhou Medical University, Guiyang, China.
² Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, China.
³ Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, China.
⁴ Department of Children Rehabilitation, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁵ Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁶ National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁷ China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁸ Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁹ School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
¹⁰ Good Clinical Practice Center, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
¹¹ Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China.
¹² State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, China.

Abstract

Psychostimulants, such as methamphetamine (METH) can induce structural remodeling of synapses by remodeling presynaptic and postsynaptic morphology. Escalating or long-lasting high dose METH accounts for neurodegeneration by targeting multiple neurotransmitters. However, the effects of low dose METH on synaptic structure and the modulation mechanism remain elusive. This study aims to assess the effects of low dose (2 mg/kg) and high dose (10 mg/kg) of METH on synaptic structure alternation in hippocampus and prefrontal cortex (PFC) and to reveal the underlying mechanism involved in the process. Low dose METH promoted spine formation, synaptic number increase, post-synaptic density length elongation, and memory function. High dose of METH induced synaptic degeneration, neuronal number loss and memory impairment. Moreover, high dose, but not low dose, of METH caused gliosis in PFC and hippocampus. Mechanism-wise, low dose METH inactivated ras-related C3 botulinum toxin substrate 1 (Rac1) and activated cell division control protein 42 homolog (Cdc42); whereas high dose METH inactivated Cdc42 and activated Rac1. We provided evidence that low and high doses of METH differentially regulate synaptic plasticity in cortex and hippocampus.

Keywords: hippocampus; methamphetamine; prefrontal cortex; structural plasticity; synapse.