Abstract
Infections during gestation and the consequent maternal immune activation (MIA) increase the risk of developing neuropsychiatric disorders in infants and throughout life, including autism spectrum disorders (ASD). ASD is a neurodevelopmental disorder that affects three times more males than females and is mainly characterized by deficits in social communication and restricted interests. Consistent findings also indicate that ASD patients suffer from movement disorders, although these symptoms are not yet considered as diagnosis criteria. Here we used the double-stranded RNA analog polyinosinic:polycytidylic acid (poly I:C) MIA animal model of ASD in mice and explored its effects in males and females on social and motor behavior. We then investigated brain areas implicated in controlling and coordinating movements, namely the nigro-striatal pathway, motor cortex and cerebellum. We show that male mice are more affected by this treatment than females as they show reduced social interactions as well as motor development and coordination deficits. Reduced numbers of Purkinje cells in the cerebellum was found more widespread and within distinct lobules in males than in females. Moreover, a reduced number of neurons was found in the motor cortex of males only. These results suggest that females are better protected against developmental insults leading to ASD symptoms in mice. They also point to brain areas that may be targeted to better manage social and motor consequences of ASD.
Highlights
Autism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental disorders characterized by persistent difficulties in verbal and nonverbal communication and restricted and repetitive patterns of behavior[1]
We demonstrate that a single injection of polycytidylic acid (poly I):C to pregnant females induces long lasting abnormal social behavior in offspring and developmental delays that were accompanied by reduced numbers of Purkinje cells (PC) within the cerebellum and neurons in the motor cortex
These results indicate that both males and females exposed prenatally to poly I:C manifest developmental delays, different in nature
Summary
Autism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental disorders characterized by persistent difficulties in verbal and nonverbal communication and restricted and repetitive patterns of behavior[1]. ASD can be diagnosed during childhood and affects 3 times more males than females[2]. In the absence of biological markers, ASD is currently diagnosed based on clinical scales and there is presently no cure but only. Maternal immune activation (MIA) is known to induce several neurological and psychiatric disorders, that, symptomatically different, share some overlapping etiological and pathophysiological features[4]. These range from microcephaly, following the recently reported Zika virus infection for instance[5], to schizophrenia and ASD. Bacterial, viral or parasite infections during pregnancy[6,7] are reported to increase risks of ASD in offspring[8]. The infectious agents do not cross the placental barrier but it is rather the maternal cytokines and immune reaction that impact the fetal brain
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