Atypical antipsychotics improve dendritic spine pathology in temporal lobe cortex neurons in a developmental rodent model of schizophrenia

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-11-15 DOI:10.1016/j.bbr.2024.115341

Hiram Tendilla-Beltrán, Diana Laura Perez-Osornio, David Javier Apam-Castillejos, Gonzalo Flores

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引用次数: 0

Abstract

"Dendritic spine pathology" refers to alterations in density and morphology of dendritic spines, crucial in corticolimbic neurons in schizophrenia. These structural neuroplasticity changes contribute to the disease's neurobiological underpinnings, alongside alterations in other brain regions, such as temporal lobe cortices like the auditory cortex (Au1) and the entorhinal cortex (Ent), involved in sensory processing, memory, and learning. The neonatal ventral hippocampus lesion (NVHL) in rats exhibits behavioral abnormalities akin to schizophrenia symptoms and corticolimbic dendritic spine pathology, mitigated by atypical antipsychotic drugs (AADs) like risperidone (RISP) and olanzapine (OLZ). This study investigated NVHL-induced dendritic spine pathology in Au1 and Ent, evaluating RISP and OLZ effects. NVHL induced dendritic spine pathology mainly by reducing the dendritic spine density in Au1 and Ent neurons; both RISP and OLZ mitigated it, increasing dendritic spine density and mushroom spine population, the ones related with synaptic strengthening, while decreasing stubby spine population. These findings underscore the role of impaired neuroplasticity in the temporal lobe cortices in schizophrenia pathophysiology and highlight the relevance of the NVHL model for studying neuroplasticity mechanisms in the disease. They also contribute to the growing understanding of targeting structural and functional neuroplasticity for novel drugs in the pharmacotherapy of the disease.

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非典型抗精神病药物可改善精神分裂症发育啮齿动物模型中颞叶皮层神经元树突棘的病理变化。

"树突棘病理学 "是指树突棘密度和形态的改变，对精神分裂症患者的皮质边缘神经元至关重要。这些结构性神经可塑性变化是该疾病的神经生物学基础，同时也是其他脑区发生变化的原因，如颞叶皮层，如听觉皮层（Au1）和内视网膜皮层（Ent），它们参与感觉处理、记忆和学习。新生儿腹侧海马损伤（NVHL）大鼠表现出类似精神分裂症症状的行为异常和皮质边缘树突棘病理学，而利培酮（RISP）和奥氮平（OLZ）等非典型抗精神病药物（AADs）可减轻这种异常。本研究调查了NVHL诱导的Au1和Ent树突棘病理学，评估了利培酮和奥氮平的作用。NVHL主要通过降低Au1和Ent神经元的树突棘密度诱导树突棘病理变化；RISP和OLZ都能减轻这种病理变化，增加树突棘密度和蘑菇棘数量（与突触强化有关），同时减少短棘数量。这些发现强调了颞叶皮层神经可塑性受损在精神分裂症病理生理学中的作用，并突出了NVHL模型对研究该病神经可塑性机制的意义。这些研究还有助于加深人们对针对神经结构和功能可塑性的新型药物在精神分裂症药物治疗中的作用的认识。

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.