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

"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.