Proteomic Analysis Reveals the Neurotoxic Effects of Chronic Methamphetamine Self-Administration-Induced Cognitive Impairments and the Role of Melatonin-Enhanced Restorative Process during Methamphetamine Withdrawal
Issued Date
2023-01-01
Resource Type
ISSN
15353893
eISSN
15353907
Scopus ID
2-s2.0-85172912303
Pubmed ID
37676068
Journal Title
Journal of Proteome Research
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Proteome Research (2023)
Suggested Citation
Polvat T., Prasertporn T., Na Nakorn P., Pannengpetch S., Suwanjang W., Panmanee J., Ngampramuan S., Cornish J.L., Chetsawang B. Proteomic Analysis Reveals the Neurotoxic Effects of Chronic Methamphetamine Self-Administration-Induced Cognitive Impairments and the Role of Melatonin-Enhanced Restorative Process during Methamphetamine Withdrawal. Journal of Proteome Research (2023). doi:10.1021/acs.jproteome.3c00502 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/90354
Title
Proteomic Analysis Reveals the Neurotoxic Effects of Chronic Methamphetamine Self-Administration-Induced Cognitive Impairments and the Role of Melatonin-Enhanced Restorative Process during Methamphetamine Withdrawal
Author's Affiliation
Other Contributor(s)
Abstract
Cognitive flexibility is a crucial ability in humans that can be affected by chronic methamphetamine (METH) addiction. The present study aimed to elucidate the mechanisms underlying cognitive impairment in mice chronically administered METH via an oral self-administration method. Further, the effect of melatonin treatment on recovery of METH-induced cognitive impairment was also investigated. Cognitive performance of the mice was assessed using an attentional set shift task (ASST), and possible underlying neurotoxic mechanisms were investigated by proteomic and western blot analysis of the prefrontal cortex (PFC). The results showed that mice-administered METH for 21 consecutive days exhibited poor cognitive performance compared to controls. Cognitive deficit in mice partly recovered after METH withdrawal. In addition, mice treated with melatonin during METH withdrawal showed a higher cognitive recovery than vehicle-treated METH withdrawal mice. Proteomic and western blot analysis revealed that METH self-administration increased neurotoxic markers, including disruption to the regulation of mitochondrial function, mitophagy, and decreased synaptic plasticity. Treatment with melatonin during withdrawal restored METH-induced mitochondria and synaptic impairments. These findings suggest that METH-induced neurotoxicity partly depends on mitochondrial dysfunction leading to autophagy-dependent cell death and that the recovery of neurological impairments may be enhanced by melatonin treatment during the withdrawal period.