Potential Cross Talk between Autism Risk Genes and Neurovascular Molecules: A Pilot Study on Impact of Blood Brain Barrier Integrity.

Autism Spectrum Disorder (ASD) is a common pediatric neurobiological disorder with up to 80% of genetic etiologies. Systems biology approaches may make it possible to test novel therapeutic strategies targeting molecular pathways to alleviate ASD symptoms. A clinical database of autism subjects was queried for individuals with a copy number variation (CNV) on microarray, Vineland, and Parent Concern Questionnaire scores.

Intravital assessment of precapillary pulmonary arterioles of type 1 diabetic mice shows oxidative damage and increased tone in response to NOS inhibition.

Microvascular dilation, important for peripheral tissue glucose distribution, also modulates alveolar perfusion and is inhibited by loss of bioavailable nitric oxide (NO) in diabetes mellitus (DM). We hypothesized that DM-induced oxidative stress decreases bioavailable NO and pulmonary precapillary arteriolar diameter, causing endothelial injury. We examined subpleural pulmonary arterioles after acute NO synthase (NOS) inhibition with -nitro-l-arginine methyl ester (l-NAME) in streptozotocin (STZ)- and saline (CTRL)-treated C57BL/6J mice.

Potential crosstalk between sonic hedgehog-WNT signaling and neurovascular molecules: Implications for blood-brain barrier integrity in autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disease originating from combined genetic and environmental factors. Post-mortem human studies and some animal ASD models have shown brain neuroinflammation, oxidative stress, and changes in blood-brain barrier (BBB) integrity. However, the signaling pathways leading to these inflammatory findings and vascular alterations are currently unclear.

Cardiac metallothionein overexpression rescues diabetic cardiomyopathy in Akt2-knockout mice.

To efficiently prevent diabetic cardiomyopathy (DCM), we have explored and confirmed that metallothionein (MT) prevents DCM by attenuating oxidative stress, and increasing expression of proteins associated with glucose metabolism. To determine whether Akt2 expression is critical to MT prevention of DCM, mice with either global Akt2 gene deletion (Akt2-KO), or cardiomyocyte-specific overexpressing MT gene (MT-TG) or both combined (MT-TG/Akt2-KO) were used. Akt2-KO mice exhibited symptoms of DCM (cardiac remodelling and dysfunction), and reduced expression of glycogen and glucose metabolism-related proteins, despite an increase in total Akt (t-Akt) phosphorylation.