The Expression Of BDNF In The Cerebral Cortex In An Animal Model Of Autism

Autism, which becomes manifest by or before the age of three, is a neurodevolpmental disorder of with the etiology unknown. Autism is characterized by impairment of social interaction, deficiency or abnormality of speech development, limited activities and interests, repetitive stereotypic movements. Abundance of studies have being carries out on the genetic, immunologic, physiological, anatomical and biochemical factors, pregnant women being exposed to harmful factors, perinatal complications. From these studies, it is well drawn out that genetic and environmental factors played an important role in autism. However, the pathogenesis of autismremains still unknown.Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is widely expressed in the developing brain. Recent reports revealed the changes in serum BDNF levels in patients with autism. Some reporters indicated that BDNF production was enhanced in autism cases during the neonatal period, but others pointed out that BDNF production is reduced in the patients. In order to understand the changes of the BDNF in the autosm, the present study was designed as following.First of all, an animal model of autism was obtained in offspring of the Wistar rat that received a single intraperitoneal injection of sodium valproate (VPA) at the pregnancy day of 12.5 and tested in the weight, timing of eye opening, swimming performance, tolerance of narcotic drugs, and the appearance of the animals. The results from this part showed that animal model of autism were successfully established.In the second part of the present study, by the methods of immunohistochemistry and Western blot, the cerebral cortex BDNF levels were investigated in different age of rat. The present results demonstrated that the distribution of BDNF-immunoreaction was restricted in neurons in the model group, the number of the BDNF-immunoreactive neurons varied with aging; BDNF levels in the model group was lower than those of control group in early age. These results suggest that BDNF might be involved in the pathogenesis of autism, and the lower expressioned BDNF may affect the development of the autistic brain interfere with the abnormal behavior occur.In the third part, we examined cerebral cortex BDNF-immunorreactive neurons in vitro. The results showed that neuronal morphology did not significant difference between the model and control groups. By the BDNF immunofluorescence method, the BDNF positive neurons in model group were observed to be less than those in the control group; the immunohistochemistry in control group was seen to distribute in nuclei of the neurons, cytoplasm and processes, while it was only distributed in the nuclei and cytoplasm of the neurons in the model group. These results from in vitro also suggest the alteration of BDNF in the cerebral cortex neurons in the autism.Taking together, the expression of the BDNF in the brain of the autism changesd a lot, suggesting it might play a certain role in the pathogenetic process of autism. On the one hand, limited distribution of BDNF in neurons affects development of brain; On the other hand, the low BDNF levels result in behavioral barriers of autism.