Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core symptoms, specifically impaired social behavior, stereotypic/repetitive behaviors, and sensory/communication deficits. Although the exact pathophysiology of ASD is still unknown, host genetics, oxidative stress, and compromised blood brain barrier (BBB) have been implicated in predisposition to ASD. With regards to genetics, mutations in the genes such as CNTNAP2 have been associated with increased susceptibility of developing ASD. Although some studies observed conflicting results suggesting no association of CNTNAP2 with ASD, other investigations correlated this gene with autism. In addition, CNTNAP2 mediated signaling is generally considered to play a role in neurological disorders due to its critical role in neurodevelopment, neurotransmission, and synaptic plasticity. In this investigation, we studied BBB integrity and oxidative stress in Cntnap2−/− rats. We observed that the BBB permeability was significantly increased in Cntnap2−/− rats compared to littermate wild-type (WT) animals as determined by FITC-dextran and Evans blue assay. High levels of thiobarbituric acid reactive substances and lower amounts of reduced glutathione were observed in brain homogenates of Cntnap2−/− rats, suggesting oxidative stress. Brain sections from Cntnap2−/− rats showed intense inducible nitric oxide synthase immunostaining, which was undetectable in WT animals. Quantification of nitric oxide in brain homogenates revealed significantly high levels in Cntnap2−/− rats compared to the control group. As increased permeability of the BBB and oxidative stress have been observed in ASD individuals, our results suggest that Cntnap2−/− rats have a high construct and face validity and can be explored to develop effective therapeutic modalities.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has a high prevalence and a significant economic impact. Our knowledge regarding neurosensory disorders and co-occurring medical conditions in the ASD population is limited, particularly for autistic women. Most of the studies include male participants or do not make comparisons with their female counterparts. The objective of this systematic review article is to explore the quality of life as well as the prevalence of neurosensory disorders and co-occurring medical conditions in individuals on the spectrum, with a special focus on autistic females. The literature search was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42022330368). We concluded that numerous medical areas were of concern. Autistic females are more likely than their male counterparts with ASD to suffer from psychiatric conditions such as post-traumatic stress syndrome, depression, and eating disorders. They are also more likely to report GI-related disturbances and chronic pain. Further investigations are warranted to determine quality of life, as well as the prevalence and severity of neurosensory disorders in individuals with ASD, specifically studies comparing autistic females with their male counterparts. The information derived from these studies will help develop better support systems for individuals with autism, particularly females on the spectrum, in pursuit of improving their quality of life.