Circadian rhythms are endogenous rhythms with a 24-hour period that enable living organisms to synchronize biological functions to the ambient light regime. In the mammalian brain circadian rhythms are regulated by the photoneuroendocrine system consisting of the suprachiasmatic nucleus of hypothalamus, the pineal gland and the retina. In a combined effort involving neuroanatomical and molecular biological techniques, we are studying development and function of the circadian system of the mammalian brain.
Homeobox genes in development and adult function of the mammalian circadian neuroendocrine system. We have shown that homeobox gene-encoded transcription factors in are essential in both development and mature function of the circadian neuroendocrine system with focus on the pinealocyte, the principal melatonin-producing cell-type of the pineal gland.
The circadian system of the mammalian brain: circadian function and hormonal regulation of local peripheral clocks in the neocortex and cerebellum. We have shown that the circadian system extends from the hypothalamus into other parts of the brain, including the cerebral cortex and the cerebellum, both of which receive a circadian input from the hypothalamus. In the cerebral cortex, the circadian clock is located in neurons, as evidenced by our finding of rhythmic expression of clock genes in these cells. Our most recently published results on a novel conditional knockout mouse show that disruption of the cortical circadian clock affects monoamine signaling and induces symptoms of depression; thus, we have used a basic scientific approach to shed light on the etiology of a major psychiatric disorder.
- Hertz H, Carstensen MB, Bering T, Rohde K, Møller M, Granau AM, Coon SL, Klein DC and Rath MF (2019) The Lhx4 homeobox transcript in the rat pineal gland: adrenergic regulation and impact on transcripts encoding melatonin-synthesizing enzyme. J Pineal Res in press (IF 15.2).
- Bering T, Hertz H and Rath MF (2019) Rhythmic release of corticosterone induces circadian clock gene expression in the cerebellum. Neuroendocrinology doi:10.1159/000503720 (IF 6.8).
- Rohde K, Hertz H and Rath MF (2019) Homeobox genes in melatonin-producing pinealocytes: Otx2 and Crx act to promote hormone synthesis in the mature rat pineal gland. J Pineal Res doi:10.1111/jpi.12567 (IF 15.2).
- Bering T, Carstensen MB, Wörtwein G, Weikop P and Rath MF (2018) The circadian oscillator of the cerebral cortex: Molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons. Cereb Cortex 28:644-657 (IF 8.3).
- Rohde K, Bering T, Furukawa T and Rath MF (2017) A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse. J Neurochem 143:100-111 (IF 4.7).
- Bering T, Carstensen MB and Rath MF (2017) Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork. J Neurochem 142:841-856 (IF 4.7).
- Rath MF, Coon SL, Amaral FG, Weller JL, Møller M and Klein DC (2016) Melatonin synthesis: Acetylserotonin O-methyltransferase (ASMT) is strongly expressed in a subpopulation of pinealocytes in the male rat pineal gland. Endocrinology 157:2028-2040 (IF 4.5).
- Yamazaki F, Møller M, Fu C, Clokie SJ, Zykovich A, Coon SL, Klein DC and Rath MF (2015) The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus. Brain Struct Funct 220:1497-1509 (IF 7.8).
- Rohde K, Rovsing L, Ho AK, Møller M and Rath MF (2014) Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N- acetyltransferase (AANAT). Endocrinology 155:2966-2975 (IF 4.7).
- Rath MF, Rohde K, Fahrenkrug J and Møller M (2013) Circadian clock components in the rat neocortex: daily dynamics, localization and regulation. Brain Struct Funct 218:551-562 (IF 7.8).