Abstract

Prenatal infection during pregnancy increases the risk for developing neuropsychiatric disorders such as schizophrenia. This is linked to an inflammatory microglial phenotype in the offspring induced by maternal immune activation (MIA).

Microglia are crucial for brain development and maintenance of neuronal niches, however, whether and how their activation is involved in the regulation of neurodevelopment remains unclear.

Here, we used a MIA rodent model in which polyinosinic: polycytidylic acid (poly (I:C)) was injected into pregnant mice. We found fewer parvalbumin positive (PV+) cells and impaired GABAergic transmission in the dentate gyrus (DG), accompanied by schizophrenia-like behavior in the adult offspring. Minocycline, a potent inhibitor of microglia activation, successfully prevented the above-mentioned deficits in the offspring.

Furthermore, by using microglia-specific arginase 1 (Arg1) ablation as well as overexpression in DG, we identified a critical role of Arg1 in microglia activation to protect against poly (I:C) imparted neuropathology and altered behavior in offspring.

Taken together, our results highlight that Arg1-mediated alternative activation of microglia are potential therapeutic targets for psychiatric disorders induced by MIA.

Abstract

Prenatal infection during pregnancy increases the risk for developing neuropsychiatric disorders such as schizophrenia. This is linked to an inflammatory microglial phenotype in the offspring induced by maternal immune activation (MIA).

Microglia are crucial for brain development and maintenance of neuronal niches, however, whether and how their activation is involved in the regulation of neurodevelopment remains unclear.

Here, we used a MIA rodent model in which polyinosinic: polycytidylic acid (poly (I:C)) was injected into pregnant mice. We found fewer parvalbumin positive (PV+) cells and impaired GABAergic transmission in the dentate gyrus (DG), accompanied by schizophrenia-like behavior in the adult offspring. Minocycline, a potent inhibitor of microglia activation, successfully prevented the above-mentioned deficits in the offspring.

Furthermore, by using microglia-specific arginase 1 (Arg1) ablation as well as overexpression in DG, we identified a critical role of Arg1 in microglia activation to protect against poly (I:C) imparted neuropathology and altered behavior in offspring.

Taken together, our results highlight that Arg1-mediated alternative activation of microglia are potential therapeutic targets for psychiatric disorders induced by MIA.

ABSTRACT

The time is ripe to integrate burgeoning evidence of the important role of sensory and motor functioning in mental health within the National Institute of Mental Health’s [NIMH] Research Domain Criteria [RDoC] framework (National Institute of Mental Health, n.d.a), a multi-dimensional method of characterizing mental functioning in health and disease across all neurobiological levels of analysis ranging from genetic to behavioral. . . .

More than half of people diagnosed with one psychiatric disorder will be diagnosed with a second or third in their lifetime. About a third have four or more.

Our findings confirm that high comorbidity across some disorders in part reflects overlapping pathways of genetic risk,” said lead author Andrew Grotzinger, an assistant professor in the Department of Psychology and Neuroscience.

The finding could ultimately open the door to treatments that address multiple psychiatric disorders at once and help reshape the way diagnoses are given, he said.

“If you had a cold, you wouldn’t want to be diagnosed with coughing disorder, sneezing disorder and aching joints disorder,” Grotzinger said.

​Conclusion:   Difficulty in emotion regulation and insecure-avoidant attachment styles were more common in untreated adolescents with ADHD.

​The study findings support the view that ADHD is a heterogeneous condition and that insecure attachment style and emotional regulation should be considered in the assessment and treatment of ADHD