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Journal of Biological Rhythms
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Circadian Organization in Male Mice Lacking the Gene for Endothelial Nitric Oxide Synthase (eNOS–/–)

Lance J. Kriegsfeld

Departments of Psychology and Neuroscience, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Psychology, 406 Schermerhorn Hall, Columbia University, 1190 Amsterdam Avenue, New York, NY 10027

Deborah L. Drazen

Departments of Psychology and Neuroscience, The Johns Hopkins University, Baltimore, MD 21218, USA

Randy J. Nelson

Departments of Psychology and Neuroscience, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Psychology, 9 Townshend Hall, 1885 Neil Avenue, The Ohio State University, Columbus, OH 43210-1222

Circadian (~24 h) rhythms in physiology and behavior are generated by the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus. For these endogenous rhythms to be synchronized with the external environment, light information must be transmitted to pacemaker cells within the SCN. This transmission of light information is accomplished via a direct retino-hypothalamic tract (RHT). Nitric oxide (NO), an endogenous gas that functions as a neurotransmitter, has been implicated as a messenger necessary for photic entrainment. Three isoforms of the enzyme that form nitric oxide, NO synthase, have been identified (a) in neurons (nNOS), (b) in the endothelial lining of blood vessels (eNOS), and (c) as an inducible form in macrophages (iNOS). The present study was undertaken to determine the specific role of eNOS in circadian organization and photic entrainment. Wild-type (WT) and eNOS–/– mice were initially entrained to a 14:10 light:dark (LD) cycle. After 3 weeks, the LD cycle was phase advanced. After an additional 3 weeks, animals were held in constant darkness (DD). eNOS–/– animals did not exhibit a deficit in the ability to entrain to the LD cycle, phase-shift locomotor activity, or free-run in constant conditions. Animals held in DD were killed after light exposure during either the subjective day or the subjective night to assess c-fos induction in the SCN. Light exposure during the subjective night increased c-fos protein expression in the SCN of both WT and eNOS–/– mice relative to animals killed after light exposure during the subjective day. Taken together, these findings suggest that endothelial isoform of NOS may not be necessary for photic entrainment in mice.

Key Words: rhythm • knock-out • glutamate • NMDA • retinohypothalamic tract • suprachiasmatic nucleus • temporal cycles

Journal of Biological Rhythms, Vol. 16, No. 2, 142-148 (2001)
DOI: 10.1177/074873001129001845


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