RESUMEN
Highly prevalent in laboratory rodents, 'social' hetero-grooming behavior is translationally relevant to modeling a wide range of neuropsychiatric disorders. Here, we comprehensively evaluated all known to date mouse genes linked to aberrant hetero-grooming phenotype, and applied bioinformatics tools to construct a network of their established protein-protein interactions (PPI). We next identified several distinct molecular clusters within this complex network, including neuronal differentiation, cytoskeletal, WNT-signaling and synapsins-associated pathways. Using additional bioinformatics analyses, we further identified 'central' (hub) proteins within these molecular clusters, likely key for mouse hetero-grooming behavior. Overall, a more comprehensive characterization of intricate molecular pathways linked to aberrant rodent grooming may markedly advance our understanding of underlying cellular mechanisms and related neurological disorders, eventually helping discover novel targets for their pharmacological or gene therapy interventions.
Asunto(s)
Biología Computacional , Aseo Animal , Animales , Aseo Animal/fisiología , Ratones , Conducta Social , Simulación por Computador , Mapas de Interacción de Proteínas/fisiologíaRESUMEN
In clinical practice, epilepsy is often comorbid with the autism spectrum disorders (ASDs). This warrants a search of animal models to uncover putative overlapping neuronal mechanisms. The Krushinsky-Molodkina (KM) rat strain is one of the oldest inbred animal models for human convulsive epilepsies. We analyzed the behavioral response of adult seizure-naive KM males in three-chambered tests for social preference. We found that a presence of social stimuli (encaged unfamiliar Wistar rats of the same age and sex) evoked a reduced or reversed exploratory response in freely moving KM individuals. The epilepsy-prone rats demonstrated remarkably shortened bouts of social contacts and displayed less locomotion around the stranger rat-containing boxes, together with a pronounced freezing response. The decrease in social preference was not due to a general decrease in activity, since relative measures of activity, the index of sociability, were decreased, too. The susceptibility to audiogenic seizures was verified in the KM cohort but not seen in the control Wistar group. We propose the KM rat strain as a new animal model for comorbid ASD and epilepsy.