title: Stimulation of BIT induces a circadian phase shift of locomotor activity in rats.
abstract: Circadian rhythms of mammals are generated by a circadian oscillation of master pacemaker genes in the suprachiasmatic nucleus of the hypothalamus (SCN), and entrained by environmental factors such as 24-h light-dark cycles. We have previously shown that light exposure during the dark period enhanced tyrosine phosphorylation of brain immunoglobulin-like molecule with tyrosine-based activation motifs (BIT) in the rat SCN. To elucidate the functional roles of BIT in the circadian clock, we stimulated BIT using an anti-BIT monoclonal antibody (mAb) 1D4, which reacts with its extracellular region and induces phosphorylation of its intracellular tyrosine residues. Administration of mAb 1D4 into the third cerebral ventricle induced tyrosine phosphorylation of BIT in the SCN. Behavioral analyses showed that the SCN-injection of the antibody at CT15 induced a phase delay of the circadian rhythm of locomotor activity, and that at CT20 induced a phase advance. Pretreatment with MK801, a non-competitive antagonist of NMDARs, diminished the 1D4-induced phase shift at CT20, but not at CT15. These results suggest that BIT is involved in the entrainment of circadian rhythms through the function of NMDARs and non-NMDARs.
authors.affiliation: Division of Protein Metabolism, Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, 565, Osaka, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Nakahata
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okumura
authors.forename: Hiroto
authors.initials: H
authors.lastname: Otani
authors.forename: Juri
authors.initials: J
authors.lastname: Hamada
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Shin ichiro
authors.initials: Si
authors.lastname: Sano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nagai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000943:Antigens, Differentiation; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D011971:Receptors, Immunologic; D016194:Receptors, N-Methyl-D-Aspartate; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases