Effects of Reduced Reelin Expression and Altered Sex Steroids on Brain Circuitry and Behavior in Mice (original) (raw)

Abstract

Background: Reelin is a candidate gene for neurodevelopmental disorders such as autism and schizophrenia. Reelin haploinsufficiency in the heterozygous rl/+ mouse causes behavioral abnormalities soon after birth, consisting of decreased ultrasound vocalizations (USV) emitted by pups upon maternal separation, as well as in adult life, producing behavioral rigidity in a task requiring a change in strategy. At the anatomical level, reelin haploinsufficiency causes a loss of GABAergic inhibitory neurons, e.g. parvalbumin-positive neurons in limbic areas and basal ganglia, and Purkinje cells (PC) in the cerebellum. This PC loss is more evident in male than female mice. Objectives: 1) To characterize brain circuit abnormalities of heterozygous reeler (rl/+) mice, and their sex-dependency; 2) To unravel the mechanisms of neuronal loss in brain areas that are relevant for autism, like the cerebellum and limbic system, focusing on interactions between decreased reelin levels and sex steroids...

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