Second-generation antipsychotic olanzapine attenuates behavioral and prefrontal cortex synaptic plasticity deficits in a neurodevelopmental schizophrenia-related rat model

• Published in: Journal of chemical neuroanatomy 2022-11, Vol.125, p.102166-102166, Article 102166
• Main Authors: Apam-Castillejos, David Javier, Tendilla-Beltrán, Hiram, Vázquez-Roque, Rubén Antonio, Vázquez-Hernández, Andrea Judith, Fuentes-Medel, Estefania, García-Dolores, Fernando, Díaz, Alfonso, Flores, Gonzalo
• Format: Article
• Language: English
• Subjects: Astrocyte; Atypical antipsychotic; BDNF; Dendritic spines; NOS-2; Synaptophysin
• ISSN: 0891-0618; 1873-6300
• DOI: 10.1016/j.jchemneu.2022.102166

Second-generation antipsychotics are the drugs of choice for the treatment of neurodevelopmental-related mental diseases such as schizophrenia. Despite the effectiveness of these drugs to ameliorate some of the symptoms of schizophrenia, specifically the positive ones, the mechanisms beyond their antipsychotic effect are still poorly understood. Second-generation antipsychotics are reported to have anti-inflammatory, antioxidant and neuroplastic properties. Using the neonatal ventral hippocampus lesion (nVHL) in the rat, an accepted schizophrenia-related model, we evaluated the effect of the second-generation antipsychotic olanzapine (OLZ) in the behavioral, neuroplastic, and neuroinflammatory alterations exhibited in the nVHL animals. OLZ corrected the hyperlocomotion and impaired working memory of the nVHL rats but failed to enhance social behavior disturbances of these animals. In the prefrontal cortex (PFC), OLZ restored the pyramidal cell structural plasticity in the nVHL rats, enhancing the dendritic arbor length, the spinogenesis and the proportion of mature spines. Moreover, OLZ attenuated astrogliosis as well as some pro-inflammatory, oxidative stress, and apoptosis-related molecules in the PFC. These findings reinforce the evidence of anti-inflammatory, antioxidant, and neurotrophic mechanisms of second-generation antipsychotics in the nVHL schizophrenia-related model, which allows for the possibility of developing more specific drugs for this disorder and thus avoiding the side effects of current schizophrenia treatments. [Display omitted] •Prefrontal cortex (PFC) dysfunction underlies the schizophrenia symptoms.•The neonatal ventral hippocampus lesion (nVHL) is a schizophrenia-related animal model.•The nVHL atrophies neural morphology and generates oxidative stress in the PFC.•Olanzapine enhances the structural plasticity and the expression of synaptic-related proteins in the PFC of nVHL rats.•Olanzapine reduces astrogliosis and oxidative stress in the PFC of nVHL rats.