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Abstract <p>Depressive disorder is a highly prevalent condition whosepathogenesis remains incompletely understood. Dysregulation of theglutamatergic system is thought to play a key role in its development.Particular focus has been placed on ionotropic glutamate receptorsdue to their crucial involvement in synaptic plasticity, learning,and memory—processes commonly impaired in depression. However, existingstudies typically focus on individual, well-characterized subunitsand are conducted on model animals from a narrow age range, whichdoes not reflect the full ontogenetic diversity of the disorder. Inthis work, we investigated the expression of genes encoding NMDA(<i>Grin1</i>, <i>Grin2a</i>, <i>Grin2b</i>, <i>Grin2c</i>, <i>Grin3a</i>) and AMPA (<i>Gria1</i>, <i>Gria2</i>, <i>Gria3</i>) receptor subunits in the prefrontalcortex (PFC) of rats from three age groups (1.5 (young), 10 (adult),and 20 (elderly) months) in a model of depressive-like behavior(DLB), induced by a chronic unpredictable mild stress (CUMS) procedure.In young DLB rats, expression of <i>Grin1</i>, <i>Grin2b</i>, <i>Grin2c</i>,and <i>Gria1</i> was decreased, whereas <i>Gria2</i> expression was elevated. In elderlyrats with DLB, expression of the <i>Grin2c</i> and <i>Grin3a</i> genes was significantly increased,while in adults, <i>Grin3a</i> expressionwas decreased. Adults also showed reduced <i>Gria2</i> expression,and elderly rats showed reduced <i>Gria3</i> expression.The obtained results indicate that the development of DLB is accompaniedby significant alterations in the expression patterns of glutamatereceptor subunit genes, and these changes are divergent across agegroups. The alterations identified in young rats during the developmentof DLB suggest a compensatory response, whereas in adult and elderlyanimals, they are of a pronounced maladaptive nature. Thus, our findingsindicate distinct molecular mechanisms of depression pathogenesisat different ages, highlighting the importance of developing age-specifictherapeutic approaches.</p>

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Alterations in NMDA and AMPA Receptor Subunit Gene Expression in the Prefrontal Cortex of Rats from Different Age Groups in a Model of Depressive-Like Behavior

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • O. V. Nadei

摘要

Abstract

Depressive disorder is a highly prevalent condition whosepathogenesis remains incompletely understood. Dysregulation of theglutamatergic system is thought to play a key role in its development.Particular focus has been placed on ionotropic glutamate receptorsdue to their crucial involvement in synaptic plasticity, learning,and memory—processes commonly impaired in depression. However, existingstudies typically focus on individual, well-characterized subunitsand are conducted on model animals from a narrow age range, whichdoes not reflect the full ontogenetic diversity of the disorder. Inthis work, we investigated the expression of genes encoding NMDA(Grin1, Grin2a, Grin2b, Grin2c, Grin3a) and AMPA (Gria1, Gria2, Gria3) receptor subunits in the prefrontalcortex (PFC) of rats from three age groups (1.5 (young), 10 (adult),and 20 (elderly) months) in a model of depressive-like behavior(DLB), induced by a chronic unpredictable mild stress (CUMS) procedure.In young DLB rats, expression of Grin1, Grin2b, Grin2c,and Gria1 was decreased, whereas Gria2 expression was elevated. In elderlyrats with DLB, expression of the Grin2c and Grin3a genes was significantly increased,while in adults, Grin3a expressionwas decreased. Adults also showed reduced Gria2 expression,and elderly rats showed reduced Gria3 expression.The obtained results indicate that the development of DLB is accompaniedby significant alterations in the expression patterns of glutamatereceptor subunit genes, and these changes are divergent across agegroups. The alterations identified in young rats during the developmentof DLB suggest a compensatory response, whereas in adult and elderlyanimals, they are of a pronounced maladaptive nature. Thus, our findingsindicate distinct molecular mechanisms of depression pathogenesisat different ages, highlighting the importance of developing age-specifictherapeutic approaches.