Peripheral Blood Leukocyte Production of BDNF following Mitogen Stimulation in Early Onset and Regressive Autism

Abstract

Brain-derived neurotrophic factor (BDNF) is critical for neuronal differentiation and synaptic development. BDNF is also implicated in the development of psychological disorders including depression, bipolar disorder and schizophrenia. Previously, elevated BDNF levels were observed in neonatal blood samples from infants who were later diagnosed with autism when compared with children who developed normally, suggesting that BDNF may be involved in the development of autism. BDNF is produced by activated brain microglial cells, a cellular phenotype that shares several features with peripheral macrophages, suggesting an important role for the immune system in BDNF production. We hypothesized that under mitogenic stimulation, peripheral blood mononuclear cells obtained from children with autism may have altered BDNF production compared with age-matched typically developing control subjects. In addition, we examined the differences between the production of BDNF in classic/early-onset autism and children who had a regressive form of autism. We show here that plasma levels of BDNF levels are increased in children with autism, especially in early onset autism subjects. Furthermore, under mitogenic stimulation with PHA and LPS, BDNF production is significantly increased in children with autism compared with typically developing subjects. However, stimulation with tetanus toxoid results in a decreased response in children with autism. This data suggest that immune cell-derived production of BDNF could be an important source for the increased BDNF that is detected in some subjects with autism. As a neurotrophic factor produced by immune cells, BDNF could help elucidate the role of the immune system in neurodevelopment and neuronal maintenance, which may be dysregulated in autism.