| Autism which belongs to the pervasive developmental disorders is characterized by deficits in communication, social interaction, repetive and stereotyped behaviors and limited interests. The autistic children is usually found and diagnosed after one year old and the prevalence is not less than 1.3 in 1000 of child population, with a 4:1 predominance of males to females according to epidemiology studies. There are at least 3 million autism children in China nowadays. Although the cause of autism is still unclear, the genetic and environmental factors are said to play the important roles in it. Nongenetic factors are speculated to involve prenatal interruptions in the normal signaling pathway of brain development. Genetic causes may arise from mutations in genes along this developmental pathway.The autism individuals usually exhibit a particular visual attention or perception, which included heightened attention to visual detail and sensitivity to trivial changes in the visual environment. And they also perform difference in in visual search skills than normal individuals. The function of saccade and visual attention are morphologically related with an important structure of superior colliculus (SC), which is retinotopically organized for selecting and initiating voluntary eye movement. Structurally the SC is identified into seven layers in mammals; the superficial grey layer and the optic layer contain the neurons responding to visual stimuli from the distinct parts of the visual field, while the intermediate grey layer contains various types of neurons involved in saccade target selection and saccade generation.The saccade associated function of SC is related to a specific neuronal subpopulation which is characterized by high frequency bursts. This kind of neurons is strongly immnuoreactive for the calcium blind protein parvalbumin (PV), which project from SC to brainstem regions involved in the control of the eye, ear and head movements. PV was often found in "fast spiking" neurons with nonadapting trains of action potentials. It has been suggested that PV might regulate a Ca2+-activated K+channel involved in spike adaptation, and in SC they are project neurons in specific visual pathways and coexist with several of excitement neurotransmitters. Therefore, investigating development of the PV-immunoreactive (PV-IR) neurons in SC could contribute to understanding of the neurobiological mechanisms underlying the development of the peculiar visual attention and saccade paradigm in autism individuals. Due to this purpose, we carried out the fellowing studies:â… . The autism animal model was obtained in offspring of the Wistar rats that received a single does of valproate (VPA) intraperitoneal injection at the pregnancy day of 12.5. We examined the development situation and behaviors of the animal model. By examining the body and brain weight test, timing of eye opening, swimming performance, perception of harmful stimulation and geotaxis, we observed that this kind of animal model exhibits delayed development of brain function and deficits in perception of harmful stimulation, which is very similary to the behaviors of human autism individuals. Therefore, prenatal VPA exposure can successfully establish the autism animal model in rats.â…¡. We examnined the number of PV-IR neurons in SC at different development stages (postnatal day 10,20 and 90), by the methods of immunohistochemistry and image analysis. We observed that in animal model group the number of PV-IR neurons were increased in juvenile and decreased in adult. And before eye opening, there were few PV-IR neurons to be observed in SC.â…¢. The Western blot results also demonstrated that the expression of PV protein was increased in juvenile then decreased in adult compared with the normal control.In summary, the expression of PV protein in SC of autism animal model exhibits an age-related change. This abnormal expression pattern might be associated with the particular saccade of autism individuals. Because the PV overexpressed in early life might cause the deficit in brain functions by disturbing the normal progress of development. |
