Role and neural regulation of clock genes in the rat pineal gland: Clock modulates amplitude of rhythmic expression of Aanat encoding the melatonin-producing enzyme
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Role and neural regulation of clock genes in the rat pineal gland : Clock modulates amplitude of rhythmic expression of Aanat encoding the melatonin-producing enzyme. / Blancas-Velazquez, Aurea S.; Bering, Tenna; Bille, Signe; Rath, Martin F.
In: Journal of Pineal Research, Vol. 75, No. 2, e12893, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Role and neural regulation of clock genes in the rat pineal gland
T2 - Clock modulates amplitude of rhythmic expression of Aanat encoding the melatonin-producing enzyme
AU - Blancas-Velazquez, Aurea S.
AU - Bering, Tenna
AU - Bille, Signe
AU - Rath, Martin F.
N1 - Publisher Copyright: © 2023 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.
PY - 2023
Y1 - 2023
N2 - Circadian clock gene expression in the suprachiasmatic nucleus (SCN) controls 24 h rhythms in body functions, but clock genes are also expressed in extra-hypothalamic tissues, including the melatonin-producing pineal gland. The nocturnal increase in pineal melatonin synthesis is a hallmark in circadian biology, but the role of local clock gene oscillations in the mammalian pineal gland is unknown. The aim of this work is to determine the role of clock genes in endocrine function of the pineal gland with focus on the Aanat transcript encoding the rhythm-generating enzyme of melatonin synthesis. Using the rat as a model, we here established 24 h expression patterns of clock genes in the pineal gland in vivo. Lesion studies showed that rhythmic clock gene expression in the pineal gland to a large extent depends on the SCN; further, clock gene rhythms could be re-established in cultured pineal cells synchronized by rhythmic stimulation with norepinephrine in 12 h pulses, suggesting that pineal cells house a slave oscillator controlled by adrenergic signaling in the gland. Histological analyses showed that clock genes are expressed in pinealocytes and colocalize with Aanat transcripts, thus potentially enabling clock gene products to control cellular melatonin production. To test this, cultured pineal cells were transfected using small interfering RNA to knock down clock gene expression. While successful knockdown of Per1 had a minor effect on Aanat, Clock knockdown produced a marked overexpression of Aanat in the pinealocytes. Our study suggests that SCN-dependent rhythmic Clock gene expression in the pinealocytes regulates the daily profile of Aanat expression.
AB - Circadian clock gene expression in the suprachiasmatic nucleus (SCN) controls 24 h rhythms in body functions, but clock genes are also expressed in extra-hypothalamic tissues, including the melatonin-producing pineal gland. The nocturnal increase in pineal melatonin synthesis is a hallmark in circadian biology, but the role of local clock gene oscillations in the mammalian pineal gland is unknown. The aim of this work is to determine the role of clock genes in endocrine function of the pineal gland with focus on the Aanat transcript encoding the rhythm-generating enzyme of melatonin synthesis. Using the rat as a model, we here established 24 h expression patterns of clock genes in the pineal gland in vivo. Lesion studies showed that rhythmic clock gene expression in the pineal gland to a large extent depends on the SCN; further, clock gene rhythms could be re-established in cultured pineal cells synchronized by rhythmic stimulation with norepinephrine in 12 h pulses, suggesting that pineal cells house a slave oscillator controlled by adrenergic signaling in the gland. Histological analyses showed that clock genes are expressed in pinealocytes and colocalize with Aanat transcripts, thus potentially enabling clock gene products to control cellular melatonin production. To test this, cultured pineal cells were transfected using small interfering RNA to knock down clock gene expression. While successful knockdown of Per1 had a minor effect on Aanat, Clock knockdown produced a marked overexpression of Aanat in the pinealocytes. Our study suggests that SCN-dependent rhythmic Clock gene expression in the pinealocytes regulates the daily profile of Aanat expression.
KW - circadian
KW - clock gene
KW - melatonin synthesis
KW - pineal gland
KW - pinealocyte
U2 - 10.1111/jpi.12893
DO - 10.1111/jpi.12893
M3 - Journal article
C2 - 37349875
VL - 75
JO - Journal of Pineal Research (Print)
JF - Journal of Pineal Research (Print)
SN - 0742-3098
IS - 2
M1 - e12893
ER -
ID: 358654481