Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.

Autor: Zhang JW; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Zhou HQ; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Zhu Z; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Ding YY; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., He Y; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Wei XL; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Xiao CF; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Li YF; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Lin WP; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China., Yin DM; Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China; NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai, Shanghai, 200062, China. Electronic address: dmyin@brain.ecnu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Sep 17; Vol. 725, pp. 150272. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1016/j.bbrc.2024.150272
Abstrakt: Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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