ABSTRACT
Signaling in Autism: An Environmental Impact ............................. 52 3.2.3 Neurotrophin Signaling in Autism: Genetic Component ................ 53 3.2.4 Dual Role of Neurotrophins ............................................................. 53 3.2.5 Neurotrophin Signaling and Gender ................................................54 3.2.6 Possible Role of Neurotrophins as Targets of Future Therapies ...... 55
3.3 Conclusions ................................................................................................... 55 Acknowledgments .................................................................................................... 55 References ................................................................................................................ 55
Autism is a neurodevelopmental disorder characterized by social and language de cits, ritualistic-repetitive behaviors, and disturbance in motor functions. As concordance in monozygotic twins is less than 100% and the phenotypic expression is variable, both genetic predispositions and environmental triggers, many of which induce oxidative stress, are likely to be involved in the etiology of autism, but the cause(s) remain elusive. Data from brain imaging and head-circumference studies, as well as Purkinje cell analysis showing early brain overgrowth followed by slow brain growth and a decrease in Purkinje cell number in a subset of autistic cases suggest that regulatory mechanisms in brain growth and differentiation are abnormal
in autism. Cell proliferation, differentiation, and the elimination of an excess number of neurons produced during the course of normal brain development are regulated by neurotrophins. We have recently reported an altered expression of brain neurotrophins, and speci cally an increased level of neurotrophin 3 (NT-3) in the autistic cerebellum. Neurotrophin imbalance is likely to result in the initial overgrowth of brain tissue followed by an arrested growth resulting in abnormal brain connectivity. Here, we review the evidence for increased oxidative stress in autism, the role of neurotrophins in brain development, data supporting altered neurotrophin signaling in autism, as well as animal data suggesting both the dual role of neurotrophins in the developing brain and the possible association between oxidative stress and altered neurotrophin expression. We also address the therapeutic potential of neurotrophins in autism.
