2000 Fiscal Year Final Research Report Summary
Roles of clock genes in the circadian regulation of the suprachiasmatic nucleus
| Project/Area Number |
10670064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Yamaguchi University |
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Principal Investigator |
INOUYE Shin-ichi t. Yamaguchi University, Faculty of Science, Professor, 理学部, 教授 (10274151)
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| Project Period (FY) |
1998 – 2000
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| Keywords | circadian rhythm / suprachiasmatic nucleus / clock genes / gene expression / period / transgenic rats / entrainment / antisense oligonucleotide |
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| Research Abstract |
The suprachiasmatic nucleus of the hypothalamus contains a circadian pacemaker, that controls virtually all rhythms of 24 hr periodicity found in the physiology and biochemistry of the body. This bilateral small nucleus along the third ventricle contains about 10,000 neurons and matching number of glias, and exhibited clear day/night differences in metabolic and electrical activities. Molecular basis of the circadian rhythmicity in the suprachiasmatic nucleus has rapidly emerged in recent 5 years. recent works indicated the presence of the negative feedback loop consisted of several clock genes, including per, tim, clock, bmal1, and cry. During the period of the current grant-in-aid, we explored the roles played by per1 gene in the circadian feedback loop in the suprachiasmatic nucleus. First we administered per1 antisense oligonucleotide into the suprachiasmatic nucleus of free moving rats and found that the per1 antisense is able to reduce or block the phase shift induced by light during the subjective night. Per1 antisense injection alone did not produce phase shift of the locomotor activity rhythm. Secondly, we analyzed the rhythm in motor activity and clock gene expressions in the suprachiasmatic nucleus of per1 transgenic rats. These animals showed free running rhythms with significantly longer period and did not entrain to the light dark cycles. Clock gene expressions in per1 transgenic rats were found normal except for overexpressed per1 gene and supressed per2 gene. Altogether, these results of experiments indicate that per1 gene is involved in the light entrainment pathway in addition to rhythm generating loop of the circadian pacemaker in the suprachiasmatic nucleus.
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