Genetic contribution to microglial activation in schizophrenia.

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied.

Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated Ca entry and accelerated differentiation.

While most of the efforts to uncover mechanisms contributing to bipolar disorder (BD) focused on phenotypes at the mature neuron stage, little research has considered events that may occur during earlier timepoints of neurodevelopment. Further, although aberrant calcium (Ca) signaling has been implicated in the etiology of this condition, the possible contribution of store-operated Ca entry (SOCE) is not well understood. Here, we report Ca and developmental dysregulations related to SOCE in BD patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells (BD-NPCs) and cortical-like glutamatergic neurons.

ER stress-associated transcription factor CREB3 is essential for normal Ca, ATP, and ROS homeostasis.

In mammalian cells, mitochondrial respiration produces reactive oxygen species (ROS) such as superoxide (O), which is then converted by the SOD1 enzyme into hydrogen peroxide (HO), the predominant form of cytosolic ROS. ROS at high levels can be toxic, but below this threshold are important for physiological processes acting as a second messenger similar to Ca. Mitochondrial Ca influx from the ER increases ATP and ROS production, while ATP and ROS can regulate Ca homeostasis, leading to an intricate interplay between Ca, ROS, and ATP synthesis.

Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia.

Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of CBD coadministration with the atypical antipsychotic iloperidone (ILO) on the activity of primary cortical neuron cultures derived from the rat methylazoxymethanol acetate (MAM) model used for the study of SZ.