concanavalin-a and Autistic-Disorder

Maternal immune activation (MIA) is a potential risk factor for autism spectrum disorder (ASD) and schizophrenia (SZ). In rodents, MIA results in changes in cytokine profiles and abnormal behaviors in the offspring that model these neuropsychiatric conditions. Given the central role that mitochondria have in immunity and other metabolic pathways, we hypothesized that MIA will result in a fetal imprinting that leads to postnatal deficits in the bioenergetics of immune cells. To this end, splenocytes from adult offspring exposed gestationally to the viral mimic poly(I:C) were evaluated for mitochondrial outcomes. A significant decrease in mitochondrial ATP production was observed in poly(I:C)-treated mice (45% of controls) mainly attributed to a lower complex I activity. No differences were observed between the two groups in the coupling of electron transport to ATP synthesis, or the oxygen uptake under uncoupling conditions. Concanavalin A- (ConA-) stimulated splenocytes from poly(I:C) animals showed no statistically significant changes in cytokine levels compared to controls. The present study reports for the first time that MIA activation by poly(I:C) at early gestation, which can lead to behavioral impairments in the offspring similar to SZ and ASD, leads to long-lasting effects in the bioenergetics of splenocytes of adult offspring.

Topics: Adenosine Triphosphate; Animals; Autistic Disorder; Behavior, Animal; Concanavalin A; Cytokines; Disease Models, Animal; Electron Transport; Energy Metabolism; Female; Leukocytes; Male; Maternal Exposure; Mice; Mice, Inbred C57BL; Mitochondria; Oxygen; Poly I-C; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Risk Factors; Social Behavior; Spleen; Time Factors

We have begun an investigation on the immune systems of patients with autism in attempt to determine if immune mechanisms are involved in the development of this severe developmental disorder. A study of 31 autistic patients has revealed several immune-system abnormalities, including reduced responsiveness in the lymphocyte blastogenesis assay to phytohemagglutinin, concanavalin A, and pokeweed mitogen; decreased numbers of T lymphocytes; and an altered ratio of helper to suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism, or these changes may be an indirect reflection of the actual pathologic mechanism.

Topics: Adolescent; Adult; Anticonvulsants; Autistic Disorder; Child; Child, Preschool; Concanavalin A; Female; Humans; Leukocyte Count; Lymphocytes; Male; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory