title: Astrocyte-specific disruption of SynCAM1 signaling results in ADHD-like behavioral manifestations.
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 function results in behavioral abnormalities similar to those described in animals model of attention-deficit hyperactive disorder (ADHD), and suggest a hitherto unappreciated contribution of glial cells to the pathophysiology of this disorder.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: Ursula S
authors.initials: US
authors.lastname: Sandau
authors.forename: Zefora
authors.initials: Z
authors.lastname: Alderman
authors.forename: Gabriel
authors.initials: G
authors.lastname: Corfas
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Ojeda
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000150:complications; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007175:Impulsive Behavior / Q000150:complications; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D000661:Amphetamine