GABA Release From Central Amygdala Neurotensin Neurons Differentially Modulates Reward and Consummatory Behavior in Male and Female Mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 14, 2023

Abstract The central nucleus of the amygdala is known to play key roles in alcohol use and affect. Neurotensin neurons have been shown regulate drinking male mice. However, little about which neurotransmitters released by these cells drive consumption or whether female Here we show that knockdown GABA release from neurotensin using a Nts- cre-dependent vGAT-shRNA-based AAV strategy reduces male, but not female, This manipulation did impact avoidance behavior, except fasted novelty-suppressed feeding test, vGAT shRNA mice demonstrated increased latency feed on familiar high-value food reward, an effect driven In contrast, showed heightened sensitivity thermal stimulation. These data role for modulating rewarding substances different motivational states.

Language: Английский

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Chronic pharmacologic manipulation of dopamine transmission ameliorates metabolic disturbance in syndrome caused by mutated trappc9

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 14, 2024

Abstract Loss-of-function mutations of the gene encoding trafficking protein particle complex subunit 9 (trappc9) cause intellectual disability and obesity by unknown mechanisms. Genome-wide analysis links trappc9 to non-alcoholic fatty liver disease (NAFLD). The abrogation in mice has been shown alter density neurons containing dopamine receptor D2 (DRD2) and/or DRD1 striatum. Here, we report that deficiency resulted disruption systemic glucose homeostasis onset NAFLD, which were relieved upon chronic treatment combining DRD2 agonist quinpirole antagonist SCH23390. trappc9-deficient was restored administrating alone. Transcriptomic proteomic analyses revealed signs impairments neurotransmitter secretion mice. Brain examinations showed synthesized normally, but their dopamine-secreting had a lower abundance structures for releasing Our study suggests loss-of-function causes NAFLD constraining transmission.

Language: Английский

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Neurotensin contributes to cholestatic liver disease potentially modulating matrix metalloprotease-7

The International Journal of Biochemistry & Cell Biology, Journal Year: 2024, Volume and Issue: 170, P. 106567 - 106567

Published: March 24, 2024

Language: Английский

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Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: May 13, 2024

To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, their correlations with subjective objective sleep quality cognitive function in the patients chronic insomnia disorder (CID). Sixty-five CID were enrolled continuously fifty-six good sleepers same period served as healthy controls (HCs). Serum levels sestrin-2 measured by enzyme-linked immunosorbent assays. Sleep was assessed Pittsburgh Quality Index (PSQI) polysomnography, mood evaluated 17-item Hamilton Depression Rating Scale. General Chinese-Beijing Version Montreal Cognitive Assessment spatial memory Blue Velvet Arena Test (BVAT). Relative to HCs, sufferers had higher neurotensin (t=5.210, p<0.001) (Z=-4.169, p<0.001), lower level (Z=-2.438, p=0.015). In terms measures, positively associated total time (r=0.562, p=0.002) efficiency (r=0.588, p=0.001), negatively wake after onset (r=-0.590, p=0.001) p=0.001); percentage rapid eye movement (r=0.442, p=0.016) non-rapid stage 2 (r=-0.394, p=0.034). Adjusted for sex, age HAMD, still above but only (r=-0.446, p=0.022). However, these biomarkers showed no significant (PSQI score). mean erroneous distance BVAT. depression, MoCA score (r=-0.257, p=0.044), BVAT (r=0.270, p=0.033). The increased decreased levels, indicating neuron dysfunction, which could be related poor dysfunction objectively.

Language: Английский

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Chronic pharmacologic manipulation of dopamine transmission ameliorates metabolic disturbance in trappc9-linked brain developmental syndrome

JCI Insight, Journal Year: 2024, Volume and Issue: 9(15)

Published: June 18, 2024

Loss-of-function mutations of the gene encoding trafficking protein particle complex subunit 9 (trappc9) cause autosomal recessive intellectual disability and obesity by unknown mechanisms. Genome-wide analysis links trappc9 to non-alcoholic fatty liver disease (NAFLD). Trappc9-deficient mice have been shown appear overweight shortly after weaning. Here, we analyzed serum biochemistry histology adipose tissues determine incidence NAFLD in trappc9-deficient combined transcriptomic proteomic analyses, pharmacological studies, biochemical histological examinations postmortem mouse brains unveil mechanisms involved. We found that presented with systemic glucose homeostatic disturbance, NAFLD, which were relieved upon chronic treatment combining dopamine receptor D2 (DRD2) agonist quinpirole DRD1 antagonist SCH23390. Blood homeostasis was restored administrating alone. RNA-sequencing DRD2-containing neurons study brain synaptosomes revealed signs impaired neurotransmitter secretion mice. Biochemical studies showed synthesized normally, but their dopamine-secreting had a lower abundance structures for releasing striatum. Our suggests loss-of-function causes constraining synapse formation.

Language: Английский

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Emerging pharmacological targets for alcohol use disorder

Alcohol, Journal Year: 2024, Volume and Issue: 121, P. 103 - 114

Published: July 26, 2024

Alcohol Use Disorder (AUD) remains a challenging condition with limited effective treatment options; however new technology in drug delivery and advancements pharmacology have paved the way for discovery of novel therapeutic targets. This review explores emerging pharmacological targets that offer options management AUD, focusing on potential somatostatin (SST), vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), nociceptin (NOP), neuropeptide S (NPS). These been selected based recent preclinical clinical research, which suggest their significant roles modulating alcohol consumption related behaviors. SST dampens cortical circuits, targeting both neurons itself presents promise treating AUD various comorbidities. VIP are modulated by system an unexplored avenue addressing exposure at stages development. GLP-1 interacts dopaminergic reward reduces intake. Nociceptin modulates mesolimbic circuitry agonism antagonism receptor offers complex but promising approach to reducing consumption. NPS stands out its anxiolytic-like effects, particularly relevant anxiety associated AUD. aims synthesize current understanding these targets, highlighting developing more personalized therapies, underscores importance continued research identifying validating comorbid conditions.

Language: Английский

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Sensory Plasticity Caused by Up-down Regulation Encodes the Information of Short-term Learning and Memory

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Learning and memory are essential for animals’ well-being surviving. The underlying mechanisms a major task of neuroscience studies. In this study, we identified circuit consisting ASER, RIC, RIS, AIY, required short-term salt chemotaxis learning (SCL) in C. elegans. ASER NaCl sensation possesses ON- OFF-responses is remodeled by conditioning. RIC integrates sensory information stimulation food deprivation generates suppression its calcium response plasticity combining with interaction between RIS that recalling. We further identify the signaling pathways neurons circuit: tyramine/TYRA-2 octopamine/OCTR-1 mediate neurohumoral regulation AIY RIC; FLP-14/FRPR-10 PDF-2/PDFR-1 signalings transmission humoral from to feedback respectively. Thus, encodes SCL, which can facilitate animal adaptation dynamic environments.

Language: Английский

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Biased Allosteric Modulator of Neurotensin Receptor 1 Reduces Ethanol Drinking and Responses to Ethanol Administration in Rodents

Addiction Neuroscience, Journal Year: 2024, Volume and Issue: 13, P. 100185 - 100185

Published: Nov. 2, 2024

Language: Английский

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Peptidergic G-Protein-Coupled Receptor Signaling Systems in Cancer: Examination of Receptor Structure and Signaling to Foster Innovative Pharmacological Solutions

Future Pharmacology, Journal Year: 2024, Volume and Issue: 4(4), P. 801 - 824

Published: Nov. 11, 2024

Background. Peptidergic GPCR systems are broadly distributed in the human body and regulate numerous physiological processes by activating complex networks of intracellular biochemical events responsible for cell regulation survival. Excessive stimulation, ill-function, or blockade GPCRs produces disturbances that may cause disease should compensatory mechanisms not suffice. Methods Results. Revision updated experimental research provided an evident relationship associating peptidergic malfunction with tumor formation maintenance resulting from uncontrolled proliferation migration, colonization, inhibition apoptosis altered metabolism, increased angiogenesis tumoral tissues. Conclusion. Determination implication peptide signaling specific neoplasia is crucial to designing tailored pharmacological treatments counteract dismantle origin circuitry causing cellular disruption. In some cases, particular ligands these receptors serve as concomitant aid other physical approaches eradicate neoplasias.

Language: Английский

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Obezitenin Genetiği

SDÜ Tıp Fakültesi Dergisi, Journal Year: 2023, Volume and Issue: 30(4), P. 754 - 762

Published: Dec. 30, 2023

Obezite, genetik, çevresel faktörler ve bunların karmaşık etkileşimleri tarafından yönetilen birçok kronik hastalık ile ilişkilidir. Genetiğin obeziteye yatkınlıkta önemli rol oynadığı riskine %70'e kadar katkıda bulunabileceği tahmin edilmektedir. Yapılan genetik çalışmalar, genlerin bulunduğunu doğrulamıştır. Genlerdeki anomaliler, Bardet- Biedl Prader-Willi sendromları gibi obezite ile ilişkili bozukluklardan doğrudan sorumludur. Genetik epidemiyolojik yaklaşımlar, özellikle genom çapında ilişkilendirme çalışmaları, insan obezitesinde önemli oynayan çok sayıda geni tanımlamıştır. Gelecekte, genetiğinin daha fazla araştırılması, tedavisi için yararlı teşhis testleri geliştirmeye yardımcı olabilir. Bu derleme genetiği hakkında güncel literatür desteklenmiş bilgiler aktarılmıştır.

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