Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.
Biochem Biophys Res Commun
; 725: 150272, 2024 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-38901224
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Parvalbuminas
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Sinapses
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Córtex Pré-Frontal
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Neurônios GABAérgicos
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Interneurônios
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Ketamina
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
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Biochem. biophys. res. commun
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Biochemical and biophysical research communications
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China