Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression.

摘要: Abstract Neonatal rodents chronically treated with the tricyclic antidepressant clomipramine show depression-like behavior, which persists throughout adulthood. Therefore, this animal model is suitable to investigate pathomechanism of depression, still largely unknown at molecular level beyond monoaminergic dysfunctions. Here, we describe protein changes in prefrontal cortex neonatally clomipramine-treated adult rats correlating behavioral abnormalities. Clomipramine was administered rat pups twice daily between postnatal days 8–21, while controls received saline injections. Behavioral tests were performed on 3 months old rats. The proteomic study conducted using two-dimensional differential gel electrophoresis. We have identified 32 proteins by mass spectrometry analysis significantly altered spots. changed are related several biological functions, such as inflammation, transcription, cell metabolism and cytoskeleton organization. Among proteins, macrophage migration inhibitory factor showed largest alteration, confirmed Western blot. Macrophage widespread distribution predominantly expressed astrocytes forebrain described immunohistochemistry. conclude that neonatal exposure induces sustained modification proteome, may form basis observed behavior Biological significance It known some psychiatric disorders, autism, depression or schizophrenia be least part, developmental disorders. hypothesized treatment early stage brain development, induce rats, results pathological distortion neuronal glial network can reflected cellular proteome Thus, an unbiased proteomics experiment reveal three months after treatment. Many previously associated depressive symptoms, e.g., (MIF), alteration among proteins. Based our data, suggest a reliable effect psychoactive drugs applied sensitive phase development. Furthermore, findings support idea development induced could result phenotype leading symptoms.