NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model

Torz, Lola; Niss, Kristoffer; Lundh, Sofia; Rekling, Jens C.; Quintana, Carlos Damian; Frazier, Signe Emilie Dannulat; Mercer, Aaron J.; Cornea, Anda; Bertelsen, Charlotte Vinther; Gerstenberg, Marina Kjærgaard; Hansen, Ann Maria Kruse; Guldbrandt, Mette; Lykkesfeldt, Jens; John, Linu M.; Villaescusa, J. Carlos; Petersen, Natalia

doi:10.3390/ijms23063260

Cited by 10 publications

(2 citation statements)

References 57 publications

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“…NPFFR2 positivity was abundant in both NPY (64%) and POMC (40%) cells, but NPFFR2-expressing cells were also detected in the somatostatin-(28%), dopamine-(26%), nociception-(16%), and NPFFR1-(16%) producing neuronal populations [173,174]. Human dual ISH data demonstrated that, similarly to mice, NPFFR2 mRNA was predominantly expressed in NPY-and GABA-producing neurons of the ARC, whereas in contrast to mice, POMC neurons did not show any NPFFR2 signal [175]. These data suggest that NPFFRs are central mediators of several aspects of the regulation of homeostasis, including the stress response.…”

Section: The Chemical Nature Of Npffr-bearing Cellsmentioning

confidence: 97%

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Kovács,

Szabó,

László

et al. 2024

Cells

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The RFamide peptide family is a group of proteins that share a common C-terminal arginine–phenylalanine–amide motif. To date, the family comprises five groups in mammals: neuropeptide FF, LPXRFamides/RFamide-related peptides, prolactin releasing peptide, QRFP, and kisspeptins. Different RFamide peptides have their own cognate receptors and are produced by different cell populations, although they all can also bind to neuropeptide FF receptors with different affinities. RFamide peptides function in the brain as neuropeptides regulating key aspects of homeostasis such as energy balance, reproduction, and cardiovascular function. Furthermore, they are involved in the organization of the stress response including modulation of pain. Considering the interaction between stress and various parameters of homeostasis, the role of RFamide peptides may be critical in the development of stress-related neuropathologies. This review will therefore focus on the role of RFamide peptides as possible key hubs in stress and stress-related psychopathologies. The neurotransmitter coexpression profile of RFamide-producing cells is also discussed, highlighting its potential functional significance. The development of novel pharmaceutical agents for the treatment of stress-related disorders is an ongoing need. Thus, the importance of RFamide research is underlined by the emergence of peptidergic and G-protein coupled receptor-based therapeutic targets in the pharmaceutical industry.

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Section: The Chemical Nature Of Npffr-bearing Cellsmentioning

confidence: 97%

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Kovács,

Szabó,

László

et al. 2024

Cells

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“…However, it is known that neuronal pathways in the hypothalamus control food intake and are key regulators for both monogenic and polygenic obesity 5 . Several human stem cell-derived hypothalamic neuron models have been developed [7][8][9][10][11] and used to investigate the molecular basis of body weight regulation 7,[11][12][13][14][15][16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR ofFAIM2

Littleton,

Trang,

Volpe

et al. 2023

Preprint

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SUMMARYThe ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region withinFAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence oncis-regulation within the genomic region. We implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches. Using a luciferase reporter assay in human primary astrocytes, we observed allele-specificcis-regulatory activity of the immediate region harboring rs7132908. Motivated by this finding, we went on to generate isogenic human embryonic stem cell lines homozygous for either rs7132908 allele with CRISPR-Cas9 homology-directed repair to assess changes in gene expression due to genotype and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. We observed that the rs7132908 obesity risk allele influenced the expression ofFAIM2along with other genes, decreased the proportion of neurons produced during differentiation, up-regulated cell death gene sets, and conversely down-regulated neuron differentiation gene sets. We have therefore functionally validated rs7132908 as a causal obesity variant which temporally regulates nearby effector genes at the ch12q13 locus and influences neurodevelopment and survival.

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Connectivity and molecular profiles of Foxp2‐ and Dbx1‐lineage neurons in the accessory olfactory bulb and medial amygdala

Prakash,

Matos,

Sebaoui

et al. 2023

J of Comparative Neurology

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In terrestrial vertebrates, the olfactory system is divided into main (MOS) and accessory (AOS) components that process both volatile and nonvolatile cues to generate appropriate behavioral responses. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the vomeronasal organ (VNO), the accessory olfactory bulb (AOB), and the medial amygdala (MeA), we reveal that populations of neurons in the AOS can be molecularly subdivided based on their ongoing or prior expression of the transcription factors Foxp2 or Dbx1, which delineate separate populations of GABAergic output neurons in the MeA. We show that a majority of AOB neurons that project directly to the MeA are of the Foxp2 lineage. Using single‐neuron patch‐clamp electrophysiology, we further reveal that in addition to sex‐specific differences across lineage, the frequency of excitatory input to MeA Dbx1‐ and Foxp2‐lineage neurons differs between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons, and lineage and sex differences in patterns of connectivity.

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NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model

Cited by 10 publications

References 57 publications

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR ofFAIM2

Connectivity and molecular profiles of Foxp2‐ and Dbx1‐lineage neurons in the accessory olfactory bulb and medial amygdala

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