Invited Review for the special issue of PEPTIDES, “A centennial tribute to Viktor Mutt”

Peptides, Год журнала: 2025, Номер unknown, С. 171369 - 171369

Опубликована: Фев. 1, 2025

This review describes how the classic gut hormone, cholecystokinin (CCK), should be comprehended in 2025. In early physiological tradition of studying gastrointestinal hormones, hormones were named after function that lead to their discovery. Hence, 1928, hormonal factor upper regulated gallbladder contraction was called cholecystokinin. 1968, Viktor Mutt and Erik Jorpes identified porcine structure this as an O-sulfated carboxyamidated peptide 33 amino acid residues (CCK-33). Its C-terminal bioactive heptapeptide amide turned out homologous antral gastrin. The allowed vitro synthesis fragments for studies production CCK-antibodies immunoassays immunohistochemistry. Today, these tools have revealed CCK highly complex: is a heterogenous, multifunctional messenger system, widely expressed both outside gut. Thus, gene encodes six different peptides (CCK-83, -58, -33, -22, -8, -5) are cell-specific manner non-sulfated forms. Moreover, not only hormones. They also potent neurotransmitters, paracrine growth satiety factors, anti-inflammatory cytokines, incretins, potential fertility factors useful tumor-markers. has phylogenetic history nearly 600 million years. Particular interest been given neuroscience CCK, because predominant transmitter brain, amounts surpass any other neuropeptide. Vice versa, brain main site mammals.

Язык: Английский

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Cholecystokinin in nociception and pain

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 557 - 581

Опубликована: Янв. 1, 2025

Язык: Английский

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Cholecystokinin in the central and peripheral nervous system

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 101 - 160

Опубликована: Янв. 1, 2025

Язык: Английский

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Goldfish phoenixin: (I) structural characterization, tissue distribution, and novel function as a feedforward signal for feeding-induced food intake in fish model

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Апрель 29, 2025

Phoenixin (PNX) is a novel peptide with diverse functions mediated by the orphan receptor GPR173. It also plays role in appetite control, but effect not consistent across species and mechanisms involved are still unclear. Using goldfish as model, underlying feeding regulation PNX were examined. In our study, two isoforms of PNX, PNXa PNXb, one form GPR173 cloned found to be highly conserved compared their counterparts other based on sequence alignment, phylogenetic analysis, silico protein modeling. RT-PCR, PNXa/b confirmed ubiquitously expressed at tissue level. goldfish, transcript expression liver brain areas including telencephalon, hypothalamus, optic tectum, elevated food intake suppressed fasting. Intraperitoneal (IP) intracerebroventricular (ICV) injections PNX20a PNX20b, mature peptides for PNXb respectively, both effective increasing foraging behavior, surface motility, intake. Furthermore, orexigenic factors (neuropeptide Y (NPY), agouti-related peptide, orexin, apelin) was parallel drops anorexigenic signals (cholecystokinin, pro-opiomelanocortin, corticotropin-releasing hormone, melanin-concentrating hormone) and/or tectum. same areas, (leptin adiponectin) attenuated concurrent rises levels (NPY ghrelin). after IP injection PNX20a/b, downregulation leptin, adiponectin, inhibitors noted. Our findings reveal that PNX20a/b can serve an factor goldfish. (both central peripheral) induced act within trigger consumption via differential modulation appetite-regulating receptors different areas. The responses observed may involve hepatic component repression liver. feedforward loop maintain/prolong during meal prior onset satiation response fish model.

Язык: Английский

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Characterizing dysregulations via cell-cell communications in Alzheimer’s brains using single-cell transcriptomes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 18, 2023

Abstract Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic genomic resolution by enabling scientists explore the diversity of gene expression patterns at finest resolution. Here, we leveraged large-scale publicly available single-nucleus RNA (snRNA-seq) human prefrontal cortex (PFC) from 23 AD samples 13 controls investigate cell-to-cell communication (C2C) healthy brains their perturbations AD. Specifically, first performed broad pattern analyses discovered inter-mixing cell types signaling pathways brains. Secondly, cell-type- centric analysis found that excitatory neurons have significantly increased communications inhibitory neurons, while other supporting cells globally decreased theirs all cells. Then, delved deeper with signaling-centric view, showing canonical CSF, TGFβ, CX3C are dysregulated type microglia/PVM WNT pathway its endothelial neuronal Finally, after extracting known risk genes, our intracellular revealed strong connection extracellular ligand genes APP, APOE, PSEN1 TREM2, ABCA1, APP astrocytes microglia neurons. In summary, novel advances technologies, show cellular regulated specific manner improper regulation linked connecting differences manifested Author Summary complex interplay suggests act concert through communication. Utilizing sequencing, investigated ligand-receptor pairs cell-type Our cell-type-centric With performing better explains Alzheimer’s.

Язык: Английский

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Phoenixin knockout mice show no impairment in fertility or differences in metabolic response to a high‐fat diet, but exhibit behavioral differences in an open field test

Journal of Neuroendocrinology, Год журнала: 2024, Номер 36(10)

Опубликована: Май 10, 2024

Phoenixin (PNX) is a conserved secreted peptide that was identified 10 years ago with numerous studies published on its pleiotropic functions. PNX associated estrous cycle length, protection from high-fat diet, and reduction of anxiety behavior. However, no study had yet evaluated the impact deleting in whole animal. We sought to evaluate mouse model lacking parent gene, small integral membrane protein 20 (Smim20), resulting effect reproduction, energy homeostasis, anxiety. found Smim20 knockout mice normal fertility lengths. Consistent fertility, hypothalamii showed changes levels reproduction-related genes, but male some homeostasis-related such as melanocortin receptor 4 (Mc4r). When placed wildtype responded similarly, heterozygous gained slightly less weight. an open field test box, female traveled distance outer zone, indicating alterations or locomotor In summary, homozygous did not alter modestly alters few neuroendocrine genes response especially mice. it altered behavior test. therefore may be crucial for reproductive function weight, however, we cannot rule out possible compensatory mechanisms model. Understanding role physiology ultimately lead enhanced understanding involving this enigmatic peptide.

Язык: Английский

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Substance P, NPY, CCK and their receptors in five brain regions in major depressive disorder with transcriptomic analysis of locus coeruleus neurons

European Neuropsychopharmacology, Год журнала: 2023, Номер 78, С. 54 - 63

Опубликована: Ноя. 4, 2023

Major depressive disorder (MDD) is a serious disease and burden to patients, families society. Rodent experiments human studies suggest that several neuropeptide systems are involved in mood regulation. The aim of this study two-fold: (i) monitor, with qPCR, transcript levels the substance P/tachykinin (TAC), NPY CCK bulk samples from control suicide subjects, targeting five postmortem brain regions including locus coeruleus (LC); (ii) analyse expression family transcripts LC neurons 'normal' brains by using laser capture microdissection Smart-Seq2 RNA sequencing. qPCR revealed distinct regional patterns male female controls higher for TAC system dorsal raphe nucleus LC, versus prefrontal cortex. In TAC, receptors few were increased mainly cortex LC. second on noradrenergic GAL, NPY, TAC1, CCK, TACR1 many other peptides (e.g. Cerebellin4 CARTPT) Adcyap1R1 GPR173). These data our previous results indicates tachykinin galanin may be valid targets developing antidepressant medicines. Moreover, perturbation MDD detection further receptor shed new light signalling mechanisms possibly associated disorders.

Язык: Английский

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Unraveling the Role of Cholecystokinin in Epilepsy: Mechanistic Insight Into Neuroplasticity.

Neurochemistry International, Год журнала: 2024, Номер 180, С. 105870 - 105870

Опубликована: Сен. 28, 2024

Язык: Английский

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Cholecystokinin-Expressing Interneurons in Basolateral Amygdala Mediate Stress-induced Anxiety-like Behaviors in Mice

Neurobiology of Stress, Год журнала: 2024, Номер 33, С. 100680 - 100680

Опубликована: Окт. 17, 2024

Язык: Английский

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Characterizing the SREB G protein-coupled receptor family in fish: Brain gene expression and genomic differences in upstream transcription factor binding sites

Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology, Год журнала: 2023, Номер 285, С. 111507 - 111507

Опубликована: Авг. 22, 2023

Язык: Английский

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