Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder

Autism spectrum disorder (ASD) refers to a broad spectrum of neurodevelopmental disorders characterized by three central behavioral symptoms: impaired social interaction, impaired social communication, and restricted and repetitive behaviors. However, the symptoms are heterogeneous among patients and a number of ASD mouse models have been generated containing mutations that mimic the mutations found in human patients with ASD. Each mouse model was found to display a unique set of repetitive behaviors. In this review, we summarize the repetitive behaviors of the ASD mouse models and variations found in their neural mechanisms including molecular and electrophysiological features. We also propose potential neuronal mechanisms underlying these repetitive behaviors, focusing on the role of the cortico-basal ganglia-thalamic circuits and brain regions associated with both social and repetitive behaviors. Further understanding of molecular and circuitry mechanisms of the repetitive behaviors associated with ASD is necessary to aid the development of effective treatments for these disorders

Isolated idiopathic bile ductular hyperplasia in patients with persistently abnormal liver function tests

BACKGROUND/AIMS: In routine examination of liver biopsies isolated ductular hyperplasia (IDH) may be the only histopathological change. Here we describe the clinical and immunophenotypic features of a number of cases retrospectively identified reviewing consecutive liver biopsies from five Italian centers over 4 years. METHODS: We reviewed 1235 cases biopsied for chronic liver disease (1078 for viral hepatitis). Records of cases fulfilling the inclusion criteria for IDH were reviewed to identify possible aetiologies. Biopsies showing IDH and control biopsies were studied by immunohistochemistry for cytokeratin-7, epithelial-membrane-antigen (EMA), neural-cell-adhesion-molecule (NCAM), Ki-67. RESULTS: Out of 70 biopsies fulfilling IDH criteria, 16 (22.8%) were of unknown aetiology. Patients with idiopathic IDH (age 38.2+/-11 years) were asymptomatic with mild, long-lasting ALT and/or gammaGT increases. A significant increase of well-differentiated (EMA-positive; NCAM-negative) bile ductules localized at the portal interface and inside the lobule was found in idiopathic IDH. CONCLUSIONS: Idiopathic IDH was present in 10% of adults biopsied for persistent mild liver function test abnormalities unrelated to viral hepatitis. In contrast with the ductular reaction seen in many forms of liver disease, it is characterized by well-differentiated hyperplastic ductules in absence of significant inflammation, and may represent a non-specific pattern of reaction to mild liver damages