astrocyte-specific disruption of syncam1 signaling results in adhd-like behavioral manifestationsastrocyte-specific syncam1信号中断导致adhd药物的行为表现.pdfVIP

Astrocyte-Specific Disruption of SynCAM1 Signaling Results in ADHD-Like Behavioral Manifestations 1¤ 1 3 1 1,2 Ursula S. Sandau , Zefora Alderman , Gabriel Corfas , Sergio R. Ojeda *, Jacob Raber * 1 Division of Neuroscience, Oregon National Primate Research Center, Oregon Health Science University, Beaverton, Oregon, United States of America, 2 Departments of Behavioral Neurosciences and Neurology, Oregon Health Science University, Portland, Oregon, United States of America, 3 F. M. Kirby Neurobiology Program, Harvard Medical School, Children’s Hospital, Boston, Massachusetts, United States of America Abstract SynCAM1 is an adhesion molecule involved in synaptic differentiation and organization. SynCAM1 is also expressed in astroglial cells where it mediates astrocyte-to astrocyte and glial-neuronal adhesive communication. In astrocytes, SynCAM1 is functionally linked to erbB4 receptors, which are involved in the control of both neuronal/glial development and mature neuronal and glial function. Here we report that mice carrying a dominant-negative form of SynCAM1 specifically targeted to astrocytes (termed GFAP-DNSynCAM1 mice) exhibit disrupted diurnal locomotor activity with enhanced and more frequent episodes of activity than control littermates during the day (when the animals are normally sleeping) accompanied by shorter periods of rest. GFAP-DNSynCAM1 mice also display high levels of basal activity in the dark period (the rodent’s awake/active time) that are attenuated by the psychostimulant D,L-amphetamine, and reduced anxiety levels in response to both avoidable and unavoidable provoking stimuli. These results indicate that disruption of SynCAM1-dependent astroglial func