Multimodal neuroimaging alterations in schizophrenia model rats and the modulatory effects of risperidone: a pilot study

Background The hippocampus is considered to be closely associated with the emergence of negative symptoms and cognitive impairments in schizophrenia (SCH). A single imaging modality is insufficient to capture the comprehensive structural, functional, and metabolic alterations in the hippocampus. This study employed multimodal magnetic resonance imaging (MRI) to investigate changes in hippocampal volume, white matter integrity, and metabolite levels in SCH rats, exploring the positive regulatory effects of risperidone. Methods Ten pregnant Wistar rats were randomly divided into two groups on gestational day 9: one was injected with poly(I:C) to establish SCH model, and the other received saline. Nine male offspring were selected and randomly assigned to three groups (n=3):Normal(from saline grop), SCH, and SCH+Risperidone (Treated) group (from poly(I:C)). From 76 days of age, the Treated group was administered risperidone solution by gastric lavage, whereas the other two groups received distilled water, for a 28-day period. Thereafter, multimodal MRI scans were conducted: Structural MRI (sMRI) for bilateral hippocampal volume; diffusion tensor imaging (DTI) for hippocampal FA and ADC values; and magnetic resonance spectroscopy (MRS) for metabolite-to-creatine ratios: N-acetylaspartate to creatine (NAA/Cr), choline to creatine (Cho/Cr), glutamate to creatine (Glu/Cr), myo-inositol to creatine (mI/Cr). Results Hippocampus Volume: Compared to the normal group, the SCH group exhibited a significant reduction in bilateral hippocampus volume ( P < 0.05). Risperidone-treatment significantly increased bilateral volume compared to the SCH group ( P < 0.05). DTI: In the SCH group, FA was decreased in the left ( P < 0.05) and right ( P < 0.01) hippocampus compared to normals. Conversely, ADC was increased in the right hippocampus ( P < 0.05). Following risperidone treatment, the FA was significantly increased in both hippocampus ( P < 0.05). MRS: The SCH group showed lower ratios of NAA/Cr and Glu/Cr than the normal group ( P < 0.05). Following risperidone treatment, the NAA/Cr was significantly elevated ( P < 0.01). Conclusions The Poly(I:C)-induced schizophrenia rat model exhibits reduced hippocampal volume, neuronal damage, impaired white matter integrity, and glutamatergic system dysfunction. These preliminary findings suggest a potential modulatory effect of risperidone, warranting validation in larger cohorts.