Schizophrenia-Like Behaviors Arising from Dysregulated Proline Metabolism Are Associated with Altered Neuronal Morphology and Function in Mice with Hippocampal PRODH Deficiency

Despite decades of research being conducted to understand what physiological deficits in the brain are an underlying basis psychiatric diseases like schizophrenia, it has remained difficult establish a direct causal relationship between neuronal dysfunction and specific behavioral phenotypes. Moreover, remains unclear how metabolic processes, including amino acid metabolism, affect function consequently modulate animal behaviors. PRODH, which catalyzes first step proline degradation, been reported as susceptibility gene for schizophrenia. It consistently shown that PRODH knockout mice exhibit schizophrenia-like However, whether loss directly impacts or such linked behaviors not yet examined. Herein, we ascertained dysregulated metabolism humans is associated with We then found was highly expressed oreins layer mouse dorsal hippocampus. By using AAV-mediated shRNA, depleted expression hippocampus subsequently observed hyperactivity impairments social behaviors, learning, memory these mice. Furthermore, led altered morphology both in vivo vitro. Our study demonstrates may arise from due