Evaluation of Social Memory and the CA2 Region of the Dorsal Hippocampus in a Neonatal Ventral Hippocampal Lesion (NVHL) Model for Inducing Schizophrenia in Rats

• Grant number: 25/11017-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2026
• End date: December 31, 2026
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: José de Anchieta de Castro e Horta Júnior
• Grantee: Pamela de Souza Silva
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Schizophrenia is a psychiatric disorder affecting approximately 1 in 300 individuals (0.32%) globally, according to the World Health Organization (WHO), with a prevalence ranging from 0.3% to 2.4% in Brazil. It is characterized by positive symptoms, such as delusions and hallucinations, often associated with psychotic episodes, and negative symptoms, notably affective blunting and social isolation. Neurodevelopmental models are among the experimental paradigms used to study schizophrenia, demonstrating both face and construct validity. The neonatal ventral hippocampal lesion (NVHL) model, developed in Sprague-Dawley rats, exhibits deficits in prepulse inhibition (PPI) of the auditory startle reflex, a phenomenon also observed in schizophrenic patients. Additionally, animals in this model show reduced social interaction, which may be linked to a deficit in social memory, recently associated with the CA2 region of the dorsal hippocampus.Therefore, we aim to investigate whether NVHL rats, with ventral hippocampal lesions, exhibit alterations in the CA2 region of the dorsal hippocampus. For this study, ten female rats will be bred, and their male offspring will be divided into three groups (n=15 each): control, NVHL lesion group, and sham lesion group. On postnatal day 7 (PND 7), pups will be anesthetized and secured in a modified platform attached to a Kopf stereotaxic apparatus. The NVHL group will receive a bilateral infusion of 0.3 ¿l of ibotenic acid, while the sham group will undergo the same surgical procedure without substance inoculation. The control group will remain undisturbed.To monitor the model, prepulse inhibition of the auditory startle reflex will be assessed on PND 56. Subsequently, the three-chamber test will be employed to measure rodent social interaction and social memory. On PND 75, animals will be euthanized via transcardiac perfusion, their brains collected, serially sectioned using a cryostat (30 µm thickness), and processed with the Nissl method for histological evaluation of bilateral ventral hippocampal lesions. For morphometric analysis of the CA2 region of the dorsal hippocampus, six animals from each group will be allocated to an immunohistochemistry protocol for calbindin D28K. Quantitative variables will be statistically analyzed (alpha = 0.05). (AU)