Abstract

This article proposes a link between autistic people being misperceived by the neurotypical majority and their being at risk of poor mental health and well-being.

We present a transactional account of development in which the misperceptions (and consequent behaviour) of the neurotypical majority influences the perceptions and behaviour of autistic people such that they become increasingly separate and indeed isolated from mainstream society.

This jeopardizes their mental health and prevents autistic people from developing to full potential.

The situation is not only problematical for the development of autistic people but is also to the detriment of wider society, in so far as autistic people are effectively prevented from contributing fully.

This account assumes that some (not necessarily all) autistic people yearn to be included, to be productive and to be useful.

It thus directly opposes accounts that view autism as an extreme case of diminished social motivation.

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.