Role of neural cell adhesion molecule and polysialic acid in mouse circadian clock function

• Type of Material: Article
• Authors: Huaming Shen, Kent State University; Michiko Watanabe, Case Western Reserve University; Henry Tomasiewicz, Emory University; Urs Rutishauser, Case Western Reserve University; Terry Magnuson, Case Western Reserve University; Jonathan Glass, Emory University
• Language: English
• Date: 1997-07-01
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 1997 Society for Neuroscience
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/jneurosci.17-13-05221.1997
• Title of Journal or Parent Work: Journal of Neuroscience
• Volume: 17
• Issue: 13
• Start Page: 5221
• End Page: 5229
• Grant/Funding Information: This research was supported by Air Force Office of Scientific Research Grant F49620-93-0086 (J.D.G.) and National Institutes of Health Grants HD18369, EY06107, and NS32779 (U.R.), and HD26722 (T.M.).
• Keywords: suprachiasmatic nucleus; neural cell adhesion molecule; Science & Technology; polysialic acid; Life Sciences & Biomedicine; ORGANIZATION; ADULT-RAT; CENTRAL-NERVOUS-SYSTEM; RHYTHMS; GOLDEN-HAMSTER; Neurosciences & Neurology; NCAM; SUPRACHIASMATIC NUCLEUS; circadian rhythms; mouse; OLFACTORY-BULB; MICE; TRACT; Neurosciences; endoneuraminidase
• Research Categories: Biology, Neuroscience

Abstract

The suprachiasmatic nuclei (SCN) express the highly polysialylated form of the neural cell adhesion molecule (NCAM) that has been proposed to promote plasticity in the adult brain. To investigate a role for NCAM in SCN circadian clock function, we examined the daily locomotor rhythm of mice homozygous for a mutation, Ncam(tmiCwr), which results in deletion of the NCAM-180 isoform that in brain carries polysialic acid (PSA). Mutant mice entrained well to a 12 hr light/dark cycle but exhibited a significantly shortened free-running period and longer activity duration under constant darkness (DD) than did wild-type mice. By the third week of DD treatment, circadian rhythmicity in the mutant was abolished. Immunocytochemical analyses of the mutant SCN revealed an abnormal number and distribution of vasoactive intestinal polypeptide-producing neurons, suggesting a developmental effect of the mutant phenotype; however, a direct physiological effect of the mutation on clock function was indicated by the fact that removal of PSA from adult wild-type SCN by microinjection of endoneuraminidase shortened the free-running period to a similar extent as in the mutant. Together, these data indicate critical roles for NCAM and PSA in the development and physiology of the mammalian SCN circadian clock.