Therapeutic Targets for Psychiatric Disorders & Neuro-Developmental Disorders Induced by Maternal Immune Activation:MICROGLIA

I think it is fitting that "MICROGLIA" may be therapeutic targets for Neuro-Developmental Disorders and Psychiatric Disorders.  

• It speaks to how we have had to DRILL DOWN FURTHER to get to ADEQUATE ANSWERS.

 

• It speaks volumes as to how FAR BEHIND Clinician and Societal Understandings are from where the RESEARCH is.

 

• We wouldn't put up with this if this were COVID.

 

• If we WAKE UP to the MULTI-GENERATIONAL Issues and Epigenetic Amplifiers of MATERNAL IMMUNE ACTIVATION ----
  • maybe we will BUILD ADEQUATE SYSTEMS of Translational Research and Medicine that are INTEGRATED across:
    • Physical Health Care
    • Mental Health Care, and
    • Substance Use Care

Microglial GPR56 is the molecular target of maternal immune activation-induced parvalbumin-positive interneuron deficits (May 2022)

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.

Neuroendocrine and immune pathways from pre- and perinatal stress to substance abuse - ScienceDirect
https://www.sciencedirect.com › science › article › pii

by SR Horn · 2018 · Cited by 7 — The neuroendocrine and immune systems are key mechanisms implicated in the transmission of addiction risk. We review animal and human

Modulating microglia activation prevents maternal immune activation induced schizophrenia-relevant behavior phenotypes via arginase 1 in the dentate gyrus (2020)

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.

Maternal immune activation generates anxiety in offspring
https://www.nature.com › ... › review articles

by LA Quagliato · 2021 · Cited by 5 — Abstract. Maternal immune activation (MIA) during pregnancy is recognized as an etiological risk factor for various psychiatric disorders, such

Effects of Maternal Immune Activation upon Amphetamine ...
https://search.proquest.com › openview

by BI Chobrutskiy · 2016 — Activation of the maternal innate immune response during pregnancy increases risk of schizophrenia, an illness with elevated rates of drug addiction.

Maternal Autoimmune Disease and ADHD Risk in Children
https://www.psychiatrictimes.com › view › maternal-aut...

Apr 13, 2021 — Maternal autoimmune disease is associated with increased risk of ADHD in offspring, adding evidence that adverse maternal immune function during ...