Regulation of Daily Locomotor Activity and Sleep by Hypothalamic EGF Receptor Signaling

Kramer, Achim; Yang, Fu-Chia; Snodgrass, Pamela; Li, Xiaodong; Scammell, Thomas E.; Davis, Fred C.; Weitz, Charles J.

doi:10.1126/science.1067716

Cited by 480 publications

(307 citation statements)

References 36 publications

(32 reference statements)

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“…45,46 The biology that connects mood symptoms and circadian rhythms is unknown. However, Kramer et al 47 have demonstrated that the actions of transforming growth factor-a, transduced through the EGFR, inhibit locomotor activity on the running wheel in mice and disrupt circadian cycles when infused into the third ventricle. Waved-2 mice are a naturally occurring strain with an EGFR point mutation that reduces kinase activity by more than 80%.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome association study of bipolar disorder

et al. 2008

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We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P = 1.66 Â 10 À7 ) and tetraspanin-8 (TSPAN8; P = 6.11 Â 10 À7 ). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P = 2.04 Â 10 À8 , TSPAN8; P = 7.57 Â 10 À7 and EGFR; P = 8.36 Â 10 À8 ). For replication, we genotyped 304 SNPs in family-based NIMH samples (n = 409 trios) and University of Edinburgh case-control samples (n = 365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

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Section: Discussionmentioning

confidence: 99%

Whole-genome association study of bipolar disorder

et al. 2008

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“…This suggests that the photoperiodic differences in fever duration between LD and SD reported here and elsewhere (Bilbo and Nelson, 2002;Bilbo et al, 2002b) may be due in part to entrainment of the circadian rhythm in body temperature. Given that the generation of circadian rhythms in the periphery is driven by the neural and humoral output of the SCN (Silver et al, 1996;Meyer-Bernstein et al, 1999;Kramer et al, 2001), and is almost entirely independent of any reciprocal influence by the pineal gland or melatonin (Sumova and Illnerova, 1996;Prendergast and Freeman, 1999), PINx would be expected to have little effect on photoperiodic differences in the febrile response to LPS if such differences are due solely to circadian factors.…”

Section: Discussionmentioning

confidence: 99%

Pineal-dependent and -independent effects of photoperiod on immune function in Siberian hamsters (Phodopus sungorus)

Wen

Dhabhar

Prendergast

2007

Hormones and Behavior

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Siberian hamsters (Phodopus sungorus) exhibit reproductive and immunological responses to photoperiod. Short (<10-h light/day) days induce gonadal atrophy, increase leukocyte concentrations, and attenuate thermoregulatory and behavioral responses to infection. Whereas hamster reproductive responses to photoperiod are dependent on pineal melatonin secretion, the role of the pineal in short-day induced changes in immune function is not fully understood. To examine this, adult hamsters were pinealectomized (PINx) or sham-PINx, and transferred to short days (9-h light/day; SD) or kept in their natal long-day (15-h light/day; LD) photoperiod. Intact and PINx hamsters housed in LD maintained large testes over the next 12 weeks; sham-PINx hamsters exhibited gonadal regression in SD, and PINx abolished this effect. Among pineal-intact hamsters, blood samples revealed increases in leukocyte, lymphocyte, CD62L+ lymphocyte, and T cell counts in SD relative to LD; PINx did not affect leukocyte numbers in LD hamsters, but abolished the SD increase in these measures. Hamsters were then treated with bacterial lipopolysaccharide (LPS), which induced thermoregulatory (fever), behavioral (anorexia, reductions in nest building), and somatic (weight loss) sickness responses in all groups. Among pineal-intact hamsters, febrile and behavioral responses to LPS were attenuated in SD relative to LD. PINx did not affect sickness responses to LPS in LD hamsters, but abolished the ameliorating effects of SD on behavioral responses to LPS. Surprisingly, PINx failed to abolish the effect of SD on fever. In common with the reproductive system, PINx induces the LD phenotype in most aspects of the immune system. The pineal gland is required for photoperiodic regulation of circulating leukocytes and neural-immune interactions that mediate select aspects of sickness behaviors.

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“…Whether or not this signal normally operates in a diffusible manner and/or is released synaptically requires further examination. A second candidate diffusible signal is transforming growth factor-alpha (TGF-alpha) (Kramer et al, 2001). As with PK2, TGF-alpha is expressed rhythmically in the SCN, and its administration inhibits wheel-running behavior.…”

Section: Circadian Output and Orchestration Of Endocrine Function Difmentioning

confidence: 99%

The regulation of neuroendocrine function: Timing is everything

Kriegsfeld

Silver

2006

Hormones and Behavior

129

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Hormone secretion is highly organized temporally, achieving optimal biological functioning and health. The master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates the timing of circadian rhythms, including daily control of hormone secretion. In the brain, the SCN drives hormone secretion. In some instances, SCN neurons make direct synaptic connections with neurosecretory neurons. In other instances, SCN signals set the phase of "clock genes" that regulate circadian function at the cellular level within neurosecretory cells. The protein products of these clock genes can also exert direct transcriptional control over neuroendocrine releasing factors. Clock genes and proteins are also expressed in peripheral endocrine organs providing additional modes of temporal control. Finally, the SCN signals endocrine glands via the autonomic nervous system, allowing for rapid regulation via multisynaptic pathways. Thus, the circadian system achieves temporal regulation of endocrine function by a combination of genetic, cellular, and neural regulatory mechanisms to ensure that each response occurs in its correct temporal niche. The availability of tools to assess the phase of molecular/cellular clocks and of powerful tract tracing methods to assess connections between "clock cells" and their targets provides an opportunity to examine circadian-controlled aspects of neurosecretion, in the search for general principles by which the endocrine system is organized. KeywordsCircadian; Diurnal; Endocrinel; Neurosecretion; Clock genes; Suprachiasmatic Circadian aspects of reproductionThe importance of circadian (about a day) timing in hormone production/secretion has been known since the 1950s when Everett and Sawyer determined that a stimulatory signal occurring during a narrow temporal window on the afternoon of proestrus is necessary for induction of ovulation later that night (Everett and Sawyer, 1950). Such close temporal organization is important for successful reproduction, as numerous hormone-dependent behavioral and physiological processes must be coordinated. If optimal temporal relationships are disrupted, pronounced deficits in fertility can result. For example, ovulation, behavioral estrus, fertilization, and pregnancy maintenance require a specific

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Regulation of Daily Locomotor Activity and Sleep by Hypothalamic EGF Receptor Signaling

Cited by 480 publications

References 36 publications

Whole-genome association study of bipolar disorder

Whole-genome association study of bipolar disorder

Pineal-dependent and -independent effects of photoperiod on immune function in Siberian hamsters (Phodopus sungorus)

The regulation of neuroendocrine function: Timing is everything

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