Lateralization of circadian pacemaker output: Activation of left- and right-sided luteinizing hormone-releasing hormone neurons involves a neural rather than a humoral pathway

Locomotor activity and luteinizing hormone (LH) secretion in golden hamsters share a common circadian pacemaker in the suprachiasmatic nucleus (SCN), but the rhythms do not seem to share a common output pathway from the SCN. Locomotion is believed to be driven by humoral factor(s), whereas LH secretion may depend on specific ipsilateral neural efferents from the SCN to LH releasing hormone (LHRH)-containing neurons in the preoptic area. In this paper we provide the first functional evidence for such efferents in neurologically intact hamsters by exploiting a phenomenon known as splitting in constant light, in which circa-12 hr (approximately 12 hr) locomotor activity bouts reflect an antiphase oscillation of the left and right sides of the bilaterally paired SCN. In ovariectomized, estrogen-treated (OVX + E2) female hamsters, splitting is also known to include circa-12 hr LH secretory surges. Here we show that behaviorally split OVX + E2 females exhibit a marked left-right asymmetry in immunoreactive c-Fos expression in both SCN and activated LHRH neurons, with the percentage of LHRH+/c-Fos+ double-labeled cells approximately fivefold higher on the side corresponding to the side of the SCN with higher c-Fos immunoreactivity. Our results suggest that splitting involves alternating left- and right-sided stimulation of LHRH neurons; under such circumstances, the functional activity of the neuroendocrine hypothalamus mirrors intrinsic side-to-side differences in SCN gene expression. The circadian regulation of reproductive activity depends on lateralized, point-to-point axonal projections rather than on diffusible factors

Chemocatalysis of sugars to produce lactic acid derivatives on zeolitic imidazolate frameworks

Several research studies related to biorefining have focused on developing routes for biomass conversion into biomaterials or platform molecules. In this work, the zeolitic imidazolate frameworks (ZIFs) ZIF-8 and ZIF-67 have been tested as catalysts in the conversion of sugars (sucrose, glucose and fructose) into methyl lactate. ZIF-8 and ZIF-67 have the same sodalite type zeolite structure but behaved differently in the sugar conversion in methanol due to the respective presence of Zn and Co in their structures. ZIF-8 has been found to be the most active for the conversion of sugars into methyl lactate (yield 42%) and was reused in four catalytic cycles. The chemical and physical effects caused by these cycles on the catalysts have been studied by several techniques (X-ray diffraction, thermogravimetric analyses, infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electronic microscopy and nitrogen adsorption)

Expression of the Vesicular GABA Transporter within Neuromedin S\u3csup\u3e+\u3c/sup\u3e Neurons Sustains Behavioral Circadian Rhythms

The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter Vgat from neuromedin-S (NMS)+ neurons—a subset of neurons critical for SCN function—causes arrhythmia of locomotor activity and sleep. Further, NMS-Vgat deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function, Vgat deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of Vgat led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker’s ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker

Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns

This study was conducted to determine the mechanisms implicated in the beneficial effects of apple polyphenols (APs) against diet-induced obesity in Wistar rats, described in a previous study from our group. Supplementation of high-fat sucrose diet with AP prevented adiposity increase by inhibition of adipocyte hypertrophy. Rats supplemented with AP exhibited improved glucose tolerance while adipocytes isolated from these rats showed an enhanced lipolytic response to isoproterenol. AP intake led to reduced Lep, Plin, and sterol regulatory element binding transcription factor 1 (Srebf1) mRNA levels and increased aquaporin 7 (Aqp7), adipocyte enhancer binding protein 1 (Aebp1), and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (Ppargc1a) mRNA levels in epididymal adipocytes. In addition, we found different methylation patterns of Aqp7, Lep, Ppargc1a, and Srebf1 promoters in adipocytes from apple-supplemented rats compared to high-fat sucrose fed rats. The administration of AP protects against body weight gain and fat deposition and improves glucose tolerance in rats. We propose that AP exerts the antiobesity effects through the regulation of genes involved in adipogenesis, lipolysis, and fatty acid oxidation, in a process that could be mediated in part by epigenetic mechanisms

Parkin loss of function contributes to RTP801 elevation and neurodegeneration in Parkinson"s disease

Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation of proteins within susceptible neurons that results in a slow but progressive neuronal degeneration and cell death. Here, we report that RTP801/REDD1, a pro-apoptotic negative regulator of survival kinases mTOR and Akt, is one of such parkin substrates. We observed that parkin knockdown elevated RTP801 in sympathetic neurons and neuronal PC12 cells, whereas ectopic parkin enhanced RTP801 poly-ubiquitination and proteasomal degradation. In parkin knockout mouse brains and in human fibroblasts from AR-JP patients with parkin mutations, RTP801 levels were elevated. Moreover, in human postmortem PD brains with mutated parkin, nigral neurons were highly positive for RTP801. Further consistent with the idea that RTP801 is a substrate for parkin, the two endogenous proteins interacted in reciprocal co-immunoprecipitates of cell lysates. A potential physiological role for parkin-mediated RTP801 degradation is indicated by observations that parkin protects neuronal cells from death caused by RTP801 overexpression by mediating its degradation, whereas parkin knockdown exacerbates such death. Similarly, parkin knockdown enhanced RTP801 induction in neuronal cells exposed to the Parkinson's disease mimetic 6-hydroxydopamine and increased sensitivity to this toxin. This response to parkin loss of function appeared to be mediated by RTP801 as it was abolished by RTP801 knockdown. Taken together these results indicate that RTP801 is a novel parkin substrate that may contribute to neurodegeneration caused by loss of parkin expression or activity

cGMP-Phosphodiesterase Inhibition Enhances Photic Responses and Synchronization of the Biological Circadian Clock in Rodents

The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN) and is synchronized by several environmental stimuli, mainly the light-dark (LD) cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2). The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC), cGMP and its related protein kinase (PKG). Pharmacological manipulation of cGMP by phosphodiesterase (PDE) inhibition (e.g., sildenafil) increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux) light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil) also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions

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The past, present, and future of the brain imaging data structure (BIDS)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS