The Study Of Alteration And Significance Of The Aerobic Glycolytic Enzymes Expression In The Progression Of Autism

Objective: To investigate the alteration of the aerobic glycolytic enzymes expression in the prefrontal cortex and cerebellum of autistic subjects and age-matched controls, as well as explore the role and mechanism of the alteration in the development of the disease, seek for the possible impaired links of glucose metabolism in the brain of autistic subjects, so that to provide a theoretical basis for the development of new drugs in clinical treatment of autism.Methods: 1. Using western blot to examine the protein expression of aerobic glycolytic enzymes including HK-??HK-??PFKP?GAPDH ?PKM1/2?PKM2?LDHA and PDH in the prefrontal cortex and cerebellum of autistic subjects and age-matched controls. 2. Using immunohistochemical method to quantify and localize the expression of HK-? in the prefrontal cortex of autistic subjects and age-matched controls.Results: 1. As compared to controls, the PDH expressions in prefrontal cortex of autistic subjects are significantly reduced by 22%(P<0.05). HK-?expressions in prefrontal cortex of autistic subjects are also significantly reduced by 24%(P<0.05).The expressions of other six enzymes including HK-??PFKP ?GAPDH? PKM1/2?PKM2 and LDHA show no significant changes in prefrontal cortex of autistic subjects(P>0.05). 2. As compared to controls,the PDH expressions in cerebellum of autistic subjects are significantly reduced by 30%(P<0.05).The expressions of other seven enzymes including HK-??HK-??PFKP?GAPDH? PKM1/2?PKM2 and LDHA show no significant changes in cerebellum of autistic subjects(P>0.05). 3. The data from immunohistochemistry show reduced expression(23%) of HK-?in neural cells of prefrontal cortex of autistic subjects compared with controls(P<0.05).Conclusions: There are reduced expressions of PDH in the brain of autistic subjects, which may be one of the main links of impaired glucose metabolism in the progression of autism; The reduced expressions of HK-?may be involved in the changes of PI3K/Akt/m TOR, as well as cell proliferation and apoptosis signaling pathway in the pathogenesis of autism; The impaired links of aerobic glycolysis may become new drug targets of autism.