Neuropathological changes and clinical features of autism spectrum disorder participants are similar to that reported in congenital and chronic cerebral toxoplasmosis in humans and mice

Anatomic, histopathologic, and MRI/SPET studies of autistic spectrum disorders (ASD) patients’ brains confirm existence of very early developmental deficits. In congenital and chronic murine toxoplasmosis several cerebral anomalies also have been reported, and worldwide, approximately two billion people are chronically infected with T. gondii with largely yet unknown consequences. The aim of the study was therefore to compare brain abnormalities in ASD patients with those found in mice with cerebral toxoplasmosis (CT) because this may help in understanding pathophysiology of ASD. Data from available published studies were analyzed to compare postmortem pathologic changes found in the brains of ASD patients with those of mice developed after intraperitoneal T. gondii infection. Patients with ASD had the following brain abnormalities: active neuroinflammatory process notably in cerebellum, microglial nodules, accumulation of perivascular macrophages, decreased number and size of Purkinje cells in cerebellar nuclei and inferior olive, hypoperfusion of brain. Mice with congenital toxoplasmosis also had persistent neuroinflammation and ventricular enlargement, periventricular edema, meningeal and perivascular inflammation, and focal loss of Purkinje and granule cells. In murine acquired CT, the brain anomalies included: ventricular dilatation probably reflecting loss of brain parenchyma; perivascular inflammation particularly in hippocampus, and periaqueductal/periventricular areas, Purkinje cell layer markedly disfigured with focal loss of cells; perivascular cuffing by mononuclear cells and localized microglial/inflammatory nodules. Infection of mice with different strains of T. gondii resulted in distinctive neuropathological changes and various stadium of maturity of cysts and the parasite itself, which is in line with the diversity of the autistic phenotypes. Also, the abnormalities in behavior and clinical features associated with autism resembled that reported in chronic latent toxoplasmosis in humans and rodents. All these similarities suggest that T. gondii should be regarded as an important infectious factor that may trigger development of ASD and some other neurodegenerative diseases, such as obsessive–compulsive and attention-deficit/hyperactivity disorders, and cryptogenic epilepsy. Thus, all these patients should be tested for T. gondii infection.