Using the maternal immune stimulation model of schizophrenia to investigate the therapeutic efficacy of neuromodulation techniques

Abstract

The present work used a neurodevelopmental rodent model of schizophrenia, namely the maternal immune stimulation (MIS) model, to study the potency of electrical neuromodulation techniques to ameliorate and even prevent schizophrenia-relevant behavioral and neurobiological abnormalities. Acute and focal deep brain stimulation (DBS) to the medial prefrontal cortex (mPFC) was found to be therapeutically relevant as it successfully normalized deficits in sensorimotor gating and attention selectivity apparent in the adult MIS animals. Using a longitudinal approach the development of sensorimotor gating deficits in the MIS model was traced and was found to exhibit a maturational delay, in accordance with the clinical situation. Further, this approach revealed aberrant neurochemistry profile in the mPFC during the pre-symptomatic period of adolescence, prior to the outbreak of the behavioral deficits. Thus, chronic DBS to the mPFC of adolescent MIS animals was tested and revealed that this approach could prevent the development of deficits in sensorimotor gating, attentional selectivity and reversal learning. Along with these effects, DBS was able to prevent increased lateral ventricles volume and neurochemical alterations as well as the prevention of altered microglia in this model. Finally, a non-invasive neuromodulation technique in the form of transcranial direct current stimulation (tDCS) was chronically applied during adolescence to the prefrontal cortex and revealed that tDCS prevented behavioral deficits belonging to the positive-symptomatology of schizophrenia, along with abnormal lateral ventricles volume. Taken together, this pre-clinical, translational-directed work points to the plausible efficacy of early, non-invasive, neuromodulation approach as a preventive measure for the development of schizophrenia.