A pathogenetic model of autism involving Purkinje cell loss through anti-GAD antibodies.
Autism is a medical enigma, lacking truly effective treatments. Both genetics and environmental factors are recognized as players in the development of autism spectrum disorders (ASDs). Nevertheless, the exact mechanism(s) for the development of ASDs is (are) not known primarily because current understanding about the etiology of the disease is limited. Selective loss of Purkinje cells and the cerebellar atrophies are the neurological abnormalities most consistently found in persons diagnosed with autism. Because Purkinje cells are involved in motor coordination, working memory and learning, loss of these cells are likely to cause symptoms defining behavioral parameters of ASD. Currently the mechanism(s) for the loss of Purkinje cells in the cerebella of autistic individual is (are) not understood. Here we postulate a hypothesis for the development of autistic symptoms, severity of which is based on the extent of Purkinje cell loss triggered by Glutamate acid decarboxylase antibody (GAD-Ab). This model accommodates any genetic basis of autism and immunogenic triggers resulting GAD-Ab in the blood of the mother while pregnant with the child diagnosed autistic after birth or of an individual diagnosed with autism some time in the life time. Identification and characterization of GAD-Abs from pregnant mothers with a family history of autism, from children with autistic siblings, and individuals diagnosed with autism may allow find preventive and new therapeutic avenues.
Departments of Surgery, Physiology and Biophysics, The Center for Psychiatric Neuroscience, University of Mississippi Medical Center, Jackson, MS 39216-4505, United States. urout@umsmed.edu
Ujjwal K
UK
Rout
Dirk M
DM
Dhossche
D000818:Animals; D001321:Autistic Disorder / Q000175:diagnosis* / Q000473:pathology*; D005192:Family Health; D005260:Female; D005968:Glutamate Decarboxylase / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007107:Immune System; D008431:Maternal-Fetal Exchange; D051379:Mice; D008954:Models, Biological; D008962:Models, Theoretical; D009035:Mothers; D011247:Pregnancy; D011689:Purkinje Cells / Q000166:cytology*
D005968:Glutamate Decarboxylase