The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

Uz, Tolga; Akhisaroğlu, Mustafa; Ahmed, Rafay; Manev, Hari

doi:10.1038/sj.npp.1300254

Cited by 107 publications

(113 citation statements)

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“…It has been hypothesized that it is through these "non-clock" functions that these circadian genes interact with systems involved in the development of cocaine addiction (Manev and Uz 2006;Uz et al 2003;Yuferov et al 2005b). For example, it has been reported that stimulant drug treatment produces gene expression changes in Per gene expression in the striatum without affecting the rhythmic expression in SCN (Manev and Uz 2006).…”

Section: Discussionmentioning

confidence: 99%

Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes

et al. 2008

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Alterations in gene expression in the dorsal striatum caused by chronic cocaine exposure have been implicated in the long-term behavioral changes associated with cocaine addiction. To gain further insight into the molecular alterations that occur as a result of cocaine self-administration, we conducted a microarray analysis of gene expression followed by bioinformatic gene network analysis that allowed us to identify adaptations at the level of gene expression as well as into interconnected networks. Changes in gene expression were examined in the dorsal striatum of rats 1 day after they had self-administered cocaine for 7 days under a 24-hr access, discrete trial paradigm (averaging 98 mg/kg/day). Here we report the regulation of the circadian genes Clock, Bmal1, Cryptochrome1, Period2, as well as several genes that are regulated by/associated with the circadian system (i.e., early growth response 1, dynorphin). We also observed regulation of other relevant genes (i.e., Nur77, beta catenin). These changes were then linked to curated pathways and formulated networks which identified circadian rhythm processes as affected by cocaine self-administration. These data strongly suggest involvement of circadian-associated genes in the brain's response to cocaine and may contribute to an understanding of addictive behavior including disruptions in sleep and circadian rhythmicity. Classification Molecular Brain Research SectionDisease-Related Neuroscience

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Section: Discussionmentioning

confidence: 99%

Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes

et al. 2008

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“…For example, the pineal hormone melatonin modulates the rhythm of the clock gene Per1 in the pituitary gland, striatum, and adrenal cortex (15)(16)(17). Furthermore, adrenal glucocorticoids induce Per1 expression in peripheral tissues such as the liver (18,19) and modulate the rhythm of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminal (BNST-OV) and central nucleus of the amygdala (CEA) (12,13).…”

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confidence: 99%

The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle

Perrin

Segall

Harbour

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Daily behavioral and physiological rhythms are linked to circadian oscillations of clock genes in the brain and periphery that are synchronized by the master clock in the suprachiasmatic nucleus. In addition, there are a number of inputs that can influence circadian oscillations in clock gene expression in a tissue-specific manner. Here we identify an influence on the circadian oscillation of the clock protein PER2, endogenous changes in ovarian steroids, within two nuclei of the limbic forebrain: the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. We show that the daily rhythm of PER2 expression within these nuclei but not in the suprachiasmatic nucleus, dentate gyrus, or basolateral amygdala is blunted in the metestrus and diestrus phases of the estrus cycle. The blunting of the PER2 rhythm at these phases of the cycle is abolished by ovariectomy and restored by phasic estrogen replacement suggesting that fluctuations in estrogen levels or their sequelae are necessary to produce these effects. The finding that fluctuations in ovarian hormones have area-specific effects on clock gene expression in the brain introduces a new level of organizational complexity in the control of circadian rhythms of behavior and physiology.circadian clock ͉ circadian rhythm ͉ estrogen T he core molecular mechanism generating circadian rhythms within the suprachiasmatic nucleus (SCN), the master circadian clock, is based on feedback loops among several rhythmically expressed clock genes and their protein products (1, 2). Circadian rhythms in clock gene expression are observed not only in the SCN but also in other brain areas as well as peripheral tissues. These include but are not limited to the olfactory bulb, several hypothalamic nuclei, the eyes, pituitary gland, heart, and lung (3-13). Because synchronized expression of clock genes in these tissues requires an intact SCN, it has been proposed that these oscillations in clock gene expression serve to gate circadian signals from the SCN into tissue-specific rhythmic outputs (10,12,13).In addition, there is growing evidence to suggest that circulating hormones as well as metabolic signals can modulate circadian oscillations of clock gene expression in some brain regions and peripheral structures (14). For example, the pineal hormone melatonin modulates the rhythm of the clock gene Per1 in the pituitary gland, striatum, and adrenal cortex (15-17). Furthermore, adrenal glucocorticoids induce Per1 expression in peripheral tissues such as the liver (18,19) and modulate the rhythm of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminal (BNST-OV) and central nucleus of the amygdala (CEA) (12, 13). By contrast, adrenalectomy has no effect on PER2 expression in the SCN, basolateral amygdala (BLA), or dentate gyrus (DG) (12, 13), and melatonin does not affect rhythms of clock gene expression in the SCN, limbic forebrain, eye, or heart (20). The ability of circulating hormones to modulate clock gene ...

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“…Results suggest that MEL treatment or PG prevent agerelated thymus involution through regulation of thymocyte apoptosis which, in turn, occurs through modulation of the pituitary-adrenal axis and zinc turnover determined by the pineal hormone 231 . Studies have found melatonin useful in cocaine abuse 232 , seasonal affective disorder 233,234 , delirium 235 , headache 236,237 , gallstone 238,239 , and amyotrophic lateral sclerosis 240 . Few studies have suggested melatonin as an effective radioprotective agent [241][242][243][244][245] .…”

Section: Miscellaneousmentioning

confidence: 99%

Untitled

2013

IJPSR

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ABSTRACT:Introduction: Melatonin is a neuro-hormone secreted from the pineal gland and involved in various regulatory activities in body. Ever-increasing use of melatonin supplements and enlarging research evidences make the authors undertook the review to arrive at a qualitative conclusion whether melatonin supplements can act as potential treatment options or not. Methodology: A comprehensive search was undertaken in different electronic databases using various search terms. A total of 225 studies were identified including clinical research studies and basic experiments. Data were extracted individually from the studies and compiled in the end. Results: Melatonin has been used successfully in chronic insomnia and as an anti-oxidant in cancer and other age-related neuro-degenerative disorders, especially Alzheimer's disease and Autistic disorders. Its evidences of use in other conditions remained insufficient and inconclusive. Conclusion: Melatonin therapy may be considered as efficacious and safe in insomnia and as an anti-oxidant; however, other roles needs to be evaluated in further studies.

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The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

Cited by 107 publications

References 33 publications

Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes

Gene profiling the response to repeated cocaine self-administration in dorsal striatum: A focus on circadian genes

The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle

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