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RiboTag enrichment of aBNST nociceptin neurons

ABSTRACT: We report the differential expression of genes in aBNST nociceptin neurons in comparison to the whole aBNST in mice

ORGANISM(S): Mus musculus

PROVIDER: GSE135982 | GEO | 2019/11/04

REPOSITORIES: GEO

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RiboTag enrichment of aBNST nociceptin neurons

Project description:RiboTag enrichment of aBNST nociceptin neurons

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A peptidomic approach to characterize peptides involved in cerebellar cortex development leads to the identification of the neurotrophic effects of nociceptin

Project description:The cerebellum is a brain structure involved in motor and cognitive functions. The development of the cerebellar cortex (the external part of the cerebellum) is under the control of numerous factors. Among these factors, neuropeptides including PACAP or somatostatin modulate the survival, migration and/or differentiation of cerebellar granule cells. Interestingly, such peptides contributing to cerebellar ontogenesis usually exhibit a specific transient expression profile with a low abundance at birth, a high expression level during the developmental processes, which take place within the first two postnatal weeks in rodents, and a gradual decline toward adulthood. Thus, to identify new peptides transiently expressed in the cerebellum during development, rat cerebella were sampled from birth to adulthood, and analyzed by a semi-quantitative peptidomic approach. A total of 33 peptides were found to be expressed in the cerebellum. Among these 33 peptides, 8 had a clear differential expression pattern during development, 4 of them i.e. cerebellin 2, nociceptin, somatostatin and VGF [353-372], exhibiting a high expression level during the first two postnatal weeks followed by a significative decrease at adulthood. A focus by a genomic approach on nociceptin, confirmed that the precursor mRNA is transiently expressed during the first week of life in granule neurons within the internal granule cell layer of the cerebellum, and showed that the nociceptin receptor is also actively expressed between P8 and P16 by the same neurons. Finally, functional studies revealed a new role for nociceptin, acting as a neurotrophic peptide able to promote the survival and differentiation of developing cerebellar granule neurons.

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B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity

Project description:B cells play a significant, yet underexplored, role in modulating immune responses in obesity and type 2 diabetes. In this study, we investigate the impact of B cell-derived nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in the context of obesity. Using a B cell-specific Pnoc knockout mouse model (PnocΔCD19), we demonstrate that loss of N/OFQ expression in B cells improves insulin sensitivity and glucose tolerance, particularly in the context of high-fat diet (HFD)-induced obesity. PnocΔCD19 mice exhibit a marked reduction in immune cell migration markers and macrophage recruitment in liver and adipose tissue. Mechanistically, we demonstrate that N/OFQ facilitates macrophage migration, contributing to the glucose intolerance and insulin resistance associated with obesity. Overall, the immunomodulatory properties exhibited by the N/OFQ-NOP system render it a compelling therapeutic target for metabolic inflammation.

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