Int J Biol Sci 2012; 8(7):1075-1084. doi:10.7150/ijbs.4742
Reduced Activity of Protein Kinase C in the Frontal Cortex of Subjects with Regressive Autism: Relationship with Developmental Abnormalities
1. NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA.
2. The State Key Lab of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, 22 HanKou Rd., Nanjing, People's Republic of China 210093.
Autism is a neurodevelopmental disorder with unknown etiology. In some cases, typically developing children regress into clinical symptoms of autism, a condition known as regressive autism. Protein kinases are essential for G-protein-coupled receptor-mediated signal transduction, and are involved in neuronal functions, gene expression, memory, and cell differentiation. Recently, we reported decreased activity of protein kinase A (PKA) in the frontal cortex of subjects with regressive autism. In the present study, we analyzed the activity of protein kinase C (PKC) in the cerebellum and different regions of cerebral cortex from subjects with regressive autism, autistic subjects without clinical history of regression, and age-matched control subjects. In the frontal cortex of subjects with regressive autism, PKC activity was significantly decreased by 57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as compared to non-regressed autistic subjects (p = 0.0048). PKC activity was unaffected in the temporal, parietal and occipital cortices, and in the cerebellum in both autism groups, i.e., regressive and non-regressed autism as compared to control subjects. These results suggest brain region-specific alteration of PKC activity in the frontal cortex of subjects with regressive autism. Further studies showed a negative correlation between PKC activity and restrictive, repetitive and stereotyped pattern of behavior (r= -0.084, p = 0.0363) in autistic individuals, suggesting involvement of PKC in behavioral abnormalities in autism. These findings suggest that regression in autism may be attributed, in part, to alterations in G-protein-coupled receptor-mediated signal transduction involving PKA and PKC in the frontal cortex.
Keywords: Autism, behavior, protein kinase C, protein kinases, regression, signal transduction.
Ji L, Chauhan A, Chauhan V. Reduced Activity of Protein Kinase C in the Frontal Cortex of Subjects with Regressive Autism: Relationship with Developmental Abnormalities. Int J Biol Sci 2012; 8(7):1075-1084. doi:10.7150/ijbs.4742. Available from http://www.ijbs.com/v08p1075.htm