Elevated arylalkylamine-N-acetyltransferase (AA-NAT) gene expression in medial habenular and suprachiasmatic nuclei of hibernating ground squirrels

Aug 23, 2002Brain research. Molecular brain research

Higher levels of a key sleep-related gene in brain areas controlling daily rhythms and mood in hibernating ground squirrels

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Abstract

All hibernating ground squirrels exhibited significantly elevated levels of AA-NAT mRNA (P<0.01) in specific brain regions associated with melatonin production.

AA-NAT is the enzyme responsible for synthesizing melatonin, which is involved in regulating seasonal hibernation rhythms.
Investigations focused on the expression of AA-NAT mRNA in the brains of both hibernating and non-hibernating ground squirrels.
The medial habenular nuclei and suprachiasmatic nuclei were identified as key areas for elevated AA-NAT mRNA expression during hibernation.
This study represents the first evidence of AA-NAT mRNA expression in extra-pineal sites in ground squirrels.
Up-regulation of the AA-NAT gene during hibernation may contribute to the generation and maintenance of hibernation.

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Hibernation, an adaptive response for energy conservation in mammals, involves a variety of physiological changes. Melatonin is linked with the regulation of core body temperature and intervenes in generating circadian cycles; its role in seasonal (circannual) rhythms of hibernation is explored here. Melatonin is primarily produced in the pineal gland. Since arylalkylamine-N-acetyltransferase (AA-NAT) is the rate-limiting enzyme for synthesizing melatonin, AA-NAT gene expression was investigated to assess the possible role of melatonin in hibernation. The findings presented here utilized combined in situ hybridization and immunohistochemistry methodologies to evaluate the AA-NAT mRNA expression in brains of both hibernating and non-hibernating ground squirrels. Brains were examined for the expression of AA-NAT mRNA using a oligonucleotide AA-NAT probe; antibody against neurofilament-70 (NF-70) was used as a neuronal marker. All hibernating animals expressed significantly (P<0.01) elevated levels of AA-NAT mRNA in both the epithalamic medial habenular nuclei (MHb) area and the hypothalamic suprachiasmatic nuclei (SCN), which is also known as the master biologic clock. These findings represent the first demonstration of the expression of mRNA encoding for AA-NAT in the extra-pineal (i.e. SCN and MHb) sites of thirteen-lined ground squirrels and indicate that the habenular nucleus may be an important supplementary location for melatonin biosynthesis. The data presented here indicate that AA-NAT gene is one of the few specific genes up-regulated during hibernation and suggest that elevation of its expression in SCN and MHb may play an essential role in the generation and maintenance of hibernation.

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Elevated arylalkylamine-N-acetyltransferase (AA-NAT) gene expression in medial habenular and suprachiasmatic nuclei of hibernating ground squirrels

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