Suppression of Vasoactive Intestinal Polypeptide in the Suprachiasmatic Nucleus Leads to Aging-Like Alterations in cAMP Rhythms and Activation of Gonadotropin-Releasing Hormone Neurons

Gerhold, Lynnette M.; Rosewell, Katherine L.; Wise, Phyllis M.

doi:10.1523/jneurosci.3598-04.2005

Cited by 53 publications

(43 citation statements)

References 49 publications

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“…Two SCN peptides, VIP and AVP, have long been implicated in stimulation of the reproductive axis. VIP mRNA but not AVP mRNA becomes arrhythmic in the SCN of middle-aged female hamsters (Krajnak et al, 1998), and suppression of SCN VIP in young female hamsters results in accelerated deficits in GnRH activation and an LH surge that mimic that of an aged population (Gerhold et al, 2005;Harney et al, 1996). Together, these findings suggest that age-related deficits in the neuroendocrine mechanisms mediating ovulation may result from loss of function at the level of the SCN.…”

Section: The Circadian System and Reproductive Agingmentioning

confidence: 85%

Aging in the circadian system: Considerations for health, disease prevention and longevity

Gibson

Williams

Kriegsfeld

2009

Experimental Gerontology

138

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The circadian system orchestrates internal physiology on a daily schedule to promote optimal health and maximize disease prevention. Chronic disruptions in circadian function are associated with an increase in a variety of disease states including, heart disease, ulcers, and diabetes. With advanced age, the genes regulating circadian function at the cellar level become disorganized and the ability of the brain clock to entrain to local time diminishes. As a result, aged individuals exhibit a loss of temporal coordination among bodily systems, leading to deficits in homeostasis and sub-optimal functioning. Such disruptions in the circadian system appear to accelerate the aging process and contribute to senescence, with some systems being more vulnerable than others. This review explores aging-associated changes in circadian function and examines evidence linking such alterations to adverse health consequences in late life and promotion of the aging process.

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Section: The Circadian System and Reproductive Agingmentioning

confidence: 85%

Aging in the circadian system: Considerations for health, disease prevention and longevity

Gibson

Williams

Kriegsfeld

2009

Experimental Gerontology

138

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“…Although chronic activation and the resulting effect on period are likely related to the other effects associated with VIP-VPAC2 signaling, exactly how they are related is unclear. For example, VIP-VPAC2 signaling has been shown to increase cAMP in cells (13,19,27,35), and cAMP appears to have a critical role in sustaining the circadian transcription/translation feedback loop in SCN cells (31). In addition, inhibition of adenylyl cyclase caused a lengthening of the period in vitro (PER2::LUC rhythms) and in the activity rhythms of mice when an inhibitor was infused in the brain (31).…”

Section: Discussionmentioning

confidence: 99%

Chronic stimulation of the hypothalamic vasoactive intestinal peptide receptor lengthens circadian period in mice and hamsters

Pantazopoulos

Dolatshad

Davis

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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) lack normal circadian activity, probably because of loss of synchronization among SCN neurons and a loss of rhythmicity in individual cells (2,3,6,8,17,29). Moreover, SCN transplants that are successful in restoring rhythms express VIP (24, 34), suggesting that VIP is a possible SCN output signal.In addition to possible roles in coupling and output, VIP-VIP receptor (VPAC2) signaling may be involved in transduction of photic input to SCN cells. Studies have shown that VIP pulses result in phase delays or phase advances of locomotor activity, depending on circadian time of administration (32). These effects are similar to the phase-shifting effects of light pulses. Electrophysiological investigations have shown that application of VIP, or a VPAC2 receptor agonist, have similar phase-shifting effects on the firing rates of SCN neurons (36). VIP pulses have also been shown to induce expression of the clock genes per1 and per2 (30), similar to the effect of light pulses on per gene expression.Taken together, these findings indicate that VIP mediates several important aspects of circadian rhythm regulation by the SCN. Whereas mice lacking VPAC2 or VIP show either shorter periods or complete loss of rhythmic activity (2, 7), the effect of chronic VPAC2 receptor activation has not been examined. Based on the evidence of a role for VIP-VPAC2 signaling in integrating light information to SCN neurons, together with disruptions in wheelrunning activity and synchrony of SCN neurons in vip Ϫ/Ϫ mice, we hypothesized that chronic stimulation of the VPAC2 receptor may result in lengthening of the period, similar to the effect of constant light (9). In addition, chronic stimulation of the VPAC2 receptor could result in increased or decreased synchrony among SCN cells. If synchrony is decreased, activity rhythms could be disrupted similar to knockout mice. If synchrony is increased, it is expected that the amplitude of a rhythm expressed by a population of rhythmic cells will increase. For example, this might be seen as higher peak expression of a key circadian regulatory gene, per2. Because VIP processes extend outside the SCN, VIP might also act as an output signal from the SCN. If so, chronic stimulation of the VPAC2 receptor in regions adjacent to the SCN through intraventricular infusion should affect activity levels. To test these hypotheses, we chronically infused a potent VPAC2 receptor agonist 44)] in the third ventricle of Syrian hamsters while monitoring wheel-running activity. In addition, we examined the effect of chronic application of BAY 55-9837 on period and amplitude of PER2 expression measured by bioluminescence in cultured SCN explants.

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“…Bowles, 1998;Gerhold et al, 2005). In this respect, common molecular machinery that results in ageing may occur throughout eukaryotes and the reduction in cAMP accumulation in the sectors suggests a new area for research on fungal ageing.…”

Section: Discussionmentioning

confidence: 99%

Colony sectorization of Metarhizium anisopliae is a sign of ageing

2005

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Spontaneous phenotypic degeneration resulting in sterile sectors is frequently observed when culturing filamentous fungi on artificial medium. Sterile sectors from two different strains of the insect pathogenic fungus Metarhizium anisopliae were investigated and found to contain reduced levels of cAMP and destruxins (insecticidal peptides). Microarray analysis using slides printed with 1730 clones showed that compared to wild-type, sterile sectors down-regulated 759 genes and upregulated 27 genes during growth in Sabouraud glucose broth or on insect cuticle. The differentially expressed genes are largely involved in cell metabolism (18?8 %), cell structure and function (13?6 %) and protein metabolism (8?8 %). Strong oxidative stress was demonstrated in sectorial cultures using the nitro blue tetrazolium assay and these cultures show other syndromes associated with ageing, including mitochondrial DNA alterations. However, genes involved in deoxidation and self-protection (e.g. heat-shock proteins, HSPs) were also upregulated. Further evidence of physiological adaptation by the degenerative sectorial cultures included cell-structure reorganization and the employment of additional signalling pathways. In spite of their very similar appearance, microarray analysis identified 181 genes differentially expressed between the two sectors, and the addition of exogenous cAMP only restored conidiation in one of them. Most of the differentially expressed genes were involved in catabolic or anabolic pathways, but the latter included genes for sporulation. Compared to the mammalian ageing process, sectorization in M. anisopliae showed many similarities, including similar patterns of cAMP production, oxidative stress responses and the involvement of HSPs. Thus, a common molecular machinery for ageing may exist throughout the eukaryotes. INTRODUCTIONThe ascomycete Metarhizium anisopliae is a widespread, soil-borne pathogen of insects, ticks and mites (Roberts & St Leger, 2004). Strains of this fungus are being developed for the control of pest species (Butt et al., 2001). Like many other fungi (Morrow et al., 1989;Kale & Bennett, 1992;Li et al., 1994), it frequently shows culture degeneration (sterile sectorization): a loss or reduction in sporulation and virulence with a fluffy-mycelium type growth. Fungal culture degeneration is usually irreversible and inheritable, and can result in great commercial losses (Li et al., 1994;Horgen et al., 1996;Ryan et al., 2003).Apart from the reports of secondary metabolite decline in degenerative fungal cultures (Wing et al., 1995; Guzman-dePena & Ruiz-Herrera, 1997;Ryan et al., 2002; Kale et al., 2003), little information is available to explain fungal culture instability at the molecular level. However, genomic DNA methylation was reported in a sector of Fusarium oxysporum after successive subculturing (Kim, 1997). In another case, fungal morphological instability was linked to dsRNA virus infection (Dawe & Nuss, 2001).In this study, the spontaneous sterile sectors from two genetically di...

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Suppression of Vasoactive Intestinal Polypeptide in the Suprachiasmatic Nucleus Leads to Aging-Like Alterations in cAMP Rhythms and Activation of Gonadotropin-Releasing Hormone Neurons

Cited by 53 publications

References 49 publications

Aging in the circadian system: Considerations for health, disease prevention and longevity

Aging in the circadian system: Considerations for health, disease prevention and longevity

Chronic stimulation of the hypothalamic vasoactive intestinal peptide receptor lengthens circadian period in mice and hamsters

Colony sectorization of Metarhizium anisopliae is a sign of ageing

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