Astrocyte-specific disruption of SynCAM1 signaling results in ADHD-like behavioral manifestations

Ursula S. Sandau, Zefora Alderman, Gabriel Corfas, Sergio Ojeda, Jacob Raber

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere36424
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 30 2012

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astrocytes
neuroglia
Attention Deficit Disorder with Hyperactivity
Neuroglia
Astrocytes
mice
Animals
amphetamine
scotophase
Amphetamine
Locomotion
anxiety
pathophysiology
adhesives
Adhesives
animal communication
locomotion
adhesion
Rodentia
rodents

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Astrocyte-specific disruption of SynCAM1 signaling results in ADHD-like behavioral manifestations. / Sandau, Ursula S.; Alderman, Zefora; Corfas, Gabriel; Ojeda, Sergio; Raber, Jacob.

In: PLoS One, Vol. 7, No. 4, e36424, 30.04.2012.

Research output: Contribution to journalArticle

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