نتائج البحث

1

Appetitive Behavior in the Social Transmission of Food Preference Paradigm Predicts Activation of Orexin-A producing Neurons in a Sex-Dependent Manner

المؤلفون: Cassidy A Malone, Hongjoo J. Lee, Laura A. Agee, Victoria Nemchek, Marie H. Monfils

المصدر: Neuroscience

الوصف: Orexin-producing cells in the lateral hypothalamic area have been shown to be involved in a wide variety of behavioral and cognitive functions, including the recall of appetitive associations and a variety of social behaviors. Here, we investigated the role of orexin in the acquisition and recall of socially transmitted food preferences in the rat. Rats were euthanized following either acquisition, short-term recall, or long-term recall of a socially transmitted food preference and their brains were processed for orexin-A and c-Fos expression. We found that while there were no significant differences in c-Fos expression between control and experimental subjects at any of the tested timepoints, females displayed significantly more activity in both orexinergic and non-orexinergic cells in the lateral hypothalamus. In the infralimbic cortex, we found that social behavior was significantly predictive of c-Fos expression, with social behaviors related to olfactory exploration appearing to be particularly influential. We additionally found that appetitive behavior was significantly predictive of orexin-A activity in a sex-dependent matter, with the total amount eaten correlating negatively with orexin-A/c-Fos colocalization in male rats but not female rats. These findings suggest a potential sex-specific role for the orexin system in balancing the stimulation of feeding behavior with the sleep/wake cycle.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7378843df8140c75659245a5e2f1ba56Test
https://doi.org/10.1016/j.neuroscience.2021.11.032Test

2

Nuclear organization of orexinergic neurons in the hypothalamus of a lar gibbon and a chimpanzee

المؤلفون: Chet C. Sherwood, Thomas C. Thannickal, Jordan Swiegers, Jerome M. Siegel, Therese Hård, Adhil Bhagwandin, Mads F. Bertelsen, Paul R. Manger, Victoria M. Williams

المصدر: Williams, V M, Bhagwandin, A, Swiegers, J, Bertelsen, M F, Hård, T, Thannickal, T C, Siegel, J M, Sherwood, C C & Manger, P R 2022, ' Nuclear organization of orexinergic neurons in the hypothalamus of a lar gibbon and a chimpanzee ', Anatomical Record, vol. 305, no. 6, pp. 1459-1475 . https://doi.org/10.1002/ar.24775Test
Anat Rec (Hoboken)
Anatomical record (Hoboken, N.J. : 2007), vol 305, iss 6

الوصف: Employing orexin-A immunohistochemical staining we describe the nuclear parcellation of orexinergic neurons in the hypothalami of a lar gibbon and a chimpanzee. The clustering of orexinergic neurons within the hypothalamus and the terminal networks follow the patterns generally observed in other mammals, including laboratory rodents, strepsirrhine primates and humans. The orexinergic neurons were found within three distinct clusters in the ape hypothalamus, which include the main cluster, zona incerta cluster and optic tract cluster. In addition, the orexinergic neurons of the optic tract cluster appear to extend to a more rostral and medial location than observed in other species, being observed in the tuberal region in the anterior ventromedial aspect of the hypothalamus. While orexinergic terminal networks were observed throughout the brain, high density terminal networks were observed within the hypothalamus, medial and intralaminar nuclei of the dorsal thalamus, and within the serotonergic and noradrenergic regions of the midbrain and pons, which is typical for mammals. The expanded distribution of orexinergic neurons into the tuberal region of the ape hypothalamus, is a feature that needs to be investigated in other primate species, but appears to correlate with orexin gene expression in the same region of the human hypothalamus, but these neurons are not revealed with immunohistochemical staining in humans. Thus, it appears that apes have a broader distribution of orexinergic neurons compared to other primate species, but that the neurons within this extension of the optic tract cluster in humans, while expressing the orexin gene, do not produce the neuropeptide.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2bb43173bb96adf8c3408dd3b5d0df20Test
https://doi.org/10.1002/ar.24775Test

3

Orexin receptors: Targets and applications

المؤلفون: Mirunalini Ravichandran, Subhiksha Subramanian

المصدر: Fundamental & Clinical Pharmacology. 36:72-80

الوصف: Over the years, elucidating targets from the neural circuits that can be used to treat disorders pertaining to the nervous system and extending their scope to other systems has always proved interesting to researchers. The role of various peptides and neurotransmitters have been elucidated and are being developed as therapeutic targets. Out of these, orexins are neuropeptides produced in the hypothalamus that stimulate a specific type of G-Protein coupled receptors (GPCR) called orexin receptors and bring about various physiological and pathological roles. Orexin receptors are of interest not only because of their wide applications such as insomnia, obesity, inflammatory disorders, etc. but also because of their contribution to promising aspects of drug discovery such as optogenetics and their tremendous growth from the stage of being orphans to orexins. This review will discuss in detail the structure of orexin receptors, their physiological role and various applications in disease states adding a note on agonists and antagonists and finally summarizing the recent drug approvals in the field.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3940a00d6a047f0695b9a1c4ed9a95caTest
https://doi.org/10.1111/fcp.12723Test

4

Orexin-2 receptor antagonism in the cornu ammonis 1 region of hippocampus prevented the antinociceptive responses induced by chemical stimulation of the lateral hypothalamus in the animal model of persistent pain

المؤلفون: Amir Haghparast, Farzaneh Nazari-Serenjeh, Kobra Askari, Abbas Haghparast, Pooya Pourreza, Mehdi Sadeghi

المصدر: Behavioural Pharmacology. 32:515-523

الوصف: Orexins are excitatory neuropeptides, mainly produced by neurons located in the lateral hypothalamus, which project to many brain areas. The orexinergic system plays a fundamental role in arousal, sleep/wakefulness, feeding, energy homeostasis, motivation, reward, stress and pain modulation. As a prominent part of the limbic system, the hippocampus has been involved in formalin-induced nociception modulation. Moreover, hippocampus regions express both orexin-1 (OX1) and orexin-2 (OX2) receptors. The present study investigated the role of OX2 receptors (OX2R) within the cornu ammonis 1 (CA1) region of the hippocampus in the mediation of lateral hypothalamus-induced antinociception. Fifty-three male Wistar rats were unilaterally implanted with two separate cannulae into the lateral hypothalamus and CA1. Animals were pretreated with intra-CA1 TCS OX2 29 as an OX2R antagonist before intra-lateral hypothalamus administration of carbachol (250 nM) as a muscarinic agonist for chemical stimulation of orexinergic neurons. Formalin test was used as an animal model of persistent pain, following intra-lateral hypothalamus carbachol microinjection. Results showed that the chemical stimulation of the lateral hypothalamus significantly attenuated formalin-evoked nociceptive behaviors during both phases of the formalin test, and administration of TCS OX2 29 into the CA1 blocked these antinociceptive responses in both phases, especially in the late phase. These findings suggest that OX2 receptors in the CA1 partially mediate the lateral hypothalamus-induced antinociceptive responses in persistent inflammatory pain.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f5a10a250b1b56880a27a5de753c6bcTest
https://doi.org/10.1097/fbp.0000000000000646Test

5

Exogenous orexin-A downregulates luteinizing hormone secretory activity in prepubertal female rats

المؤلفون: Anna Litwiniuk, Wojciech Bik, Boguslawa Baranowska, Małgorzata Kalisz, Alina Gajewska, Lidia Martynska, Magdalena Chmielowska

المصدر: Endokrynologia Polska. 72:238-242

الوصف: Introduction: Orexin-A is a neuropeptide synthesized in the lateral hypothalamus. Orexin-A immunoreactive fibres overlap distribution with GnRH neurons. In adult rats, orexin A is known to affect LH secretion via GnRH release modulation. Because data concerning the impact of orexin-A on the hypothalamo-pituitary axis activity are limited, we focused on the involvement of orexin-A and receptors of NPY in the modulation of LH release and LH subunit b (Lhb) mRNA expression in prepubertal female rats. Material and methods: Forty immature female Wistar rats were divided into 4 groups and received 2 intracerebroventricular (icv) microinjections of: 1 — artificial cerebrospinal fluid (CSF) (controls); 2 — CSF followed by orexin A; 3 — selective NPY receptor antagonist (BIBP) followed by CSF; 4 — BIBP followed by orexin A. One hour after the last microinjection, all rats were decapitated. Trunk blood was collected, and serum was stored at –20°C for the LH RIA examination. The adenohypophysis was immediately excised, flash-frozen, and kept at –80°C for RNA extraction. Real-time PCR amplification was carried out, and relative Lhb gene expression was calculated. Results: In comparison to the CSF-treated controls with a mean LH serum concentration of 0.40 ± 0.02 ng/mL, the mean LH serum level was diminished both after orexin-A (0.27 ± 0.01 ng/mL) and after BIBP (0.30 ± 0.02 ng/mL) icv microinjections. In the presence of BIBP, orexin-A more effectively inhibited LH release (0.20 ± 0.01 ng/mL) when compared to the BIBP-treated group. Orexin-A and BIBP exerted a consistent inhibitory effect on Lhb mRNA expression levels in the anterior pituitary gland. In comparison to the CSF-treated controls, orexin-A, and BIBP-treated females responded with, respectively, 35% and 40% reduction of Lhb mRNA expression. Orexin-A and BIBP co-administration evoked a further reduction of Lhb gene transcriptional activity. Conclusions: Orexin-A exerts a down-regulatory effect on LH synthesis and release in immature female rats. Considering that Y1R-oriented down-regulation of endogenous NPY activity did not reverse the suppressive effect of exogenous orexin-A, it might be suggested that NPY and orexin A systems can operate independently to affect gonadotropin activity in the anterior pituitary of the immature female rats.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2ea3d66cecc37091dc69f8f074fa156Test
https://doi.org/10.5603/ep.a2021.0041Test

6

Neuropeptides in the Cerebellum

المؤلفون: James S. King, Georgia A. Bishop

المصدر: Essentials of Cerebellum and Cerebellar Disorders ISBN: 9783031150692
Essentials of Cerebellum and Cerebellar Disorders ISBN: 9783319245492

مصطلحات موضوعية: Cerebellum, Purkinje cell, Neuropeptide, Climbing fiber, Golgi apparatus, Biology, Orexin, symbols.namesake, medicine.anatomical_structure, nervous system, symbols, medicine, Premovement neuronal activity, Transduction (physiology), Neuroscience

الوصف: To truly understand cerebellar function, it is essential to address the effect of the numerous peptides present within cerebellar circuits and the role they play in modulating neuronal activity in the cerebellum. To date, at least 22 neuropeptides have been identified in the cerebellum. However, relatively little is conclusively known about the modulatory role of the vast majority of these peptides. The potential role of three peptides is reviewed. Future research should focus on defining transduction pathways activated following binding of these peptides to their G-protein-coupled receptors, defining the function of peptides produced by cerebellar neurons such as Purkinje cells or Golgi cells, and describing how neuropeptides modulate cerebellar nuclear neurons, which represent the output of the cerebellum.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4999476c820a9badadb37f5dcc83a46aTest
https://doi.org/10.1007/978-3-031-15070-8_36Test

7

Paired-pulse Inhibition and Disinhibition of the Dentate Gyrus Following Orexin Receptors Inactivation in the Basolateral Amygdala

المؤلفون: Motahareh Rouhi Ardeshiri, Narges Hosseinmardi, Esmaeil Akbari

المصدر: Basic and Clinical Neuroscience Journal. 12:827-836

مصطلحات موضوعية: Clinical neuroscience, Pulse (signal processing), Dentate gyrus, Molecular neuroscience, Orexin receptor, Cellular and Molecular Neuroscience, medicine.anatomical_structure, nervous system, Disinhibition, Cellular neuroscience, medicine, Neurology (clinical), medicine.symptom, Neuroscience, Basolateral amygdala

الوصف: The Basolateral Amygdala (BLA) substantially affects neuronal transmission and synaptic plasticity processes through the dentate gyrus. Orexin neuropeptides play different roles in the sleep/wakefulness cycle, feeding, learning, and memory. The present study aimed to investigate the function of the orexin receptors of the BLA in the hippocampal local interneuron circuits.For this, the region's paired-pulse responses from the Dentate Gyrus (DG) were recorded. Within the procedure, SB-334867-A (12μg/0.5μL) and TCS-OX2-29 (10μg/0.5μL (orexin 12 receptors antagonists, respectively), were administered into both sides of the BLA areas of the rat brain. Dimethyl Sulfoxide (DMSO) was used as the solvent in the control animals with a volume of 0.5μL.Our data indicated that the Paired-pulse (PP) responses were not affected by the inactivation of the orexin receptors of the BLA.Due to not observing any significant changes in the short form of synaptic plasticity, after inactivation of the orexin system of the BLA, we hypothesize that the orexinergic fibers to the basolateral part of the amygdala influence the long-term synaptic efficacy; however, the primary processing of information in short-term plasticity model is not affected by the same system. The elementary processing of the data by the amygdala might happen through the action of other neurotransmitter systems.The neuronal transmission of DG following orexin receptors antagonism of the BLA.Paired-pulse responses were not affected by the orexin 1 receptors antagonism.Paired-pulse responses were not affected by the orexin 2 receptors antagonism.The orexinergic system has modulatory effects by sending projection fibers to several parts of the brain, such as the hippocampus and amygdala. Orexin neuropeptides activate basolateral amygdala neural circuits during different arousal states. Although, this system plays a vital role in creating appropriate behavioral reactions, the primary processing of the information in short-term plasticity model is not affected by it.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::61a5724f3ff4022d92634fa870cb0e7bTest
https://doi.org/10.32598/bcn.12.6.1460.1Test

8

The role of ventral tegmental area orexinergic afferents in depressive-like behavior in a chronic unpredictable mild stress (CUMS) mouse model

المؤلفون: Yunyun Song, Jiannan Li, Huiming Li, Danmin Miao, Min Cai

المصدر: Biochemical and Biophysical Research Communications. 579:22-28

الوصف: Orexin has been implicated in comorbid diseases of depression, making it a promising target for anti-depression treatment. Although orexin neurons exhibit abnormal activity in depression, the neurocircuit mechanism of orexin remains unclear. As one of the important downstream factors of orexin neurons, the ventral tegmental area (VTA) is considered crucial to the mechanism of depression. However, the role of VTA orexinergic afferents in depression remains unclear. In this study, we applied a combination of opto/chemogenetic and neuropharmacology methods to investigate whether the VTA orexinergic afferents participate in the pathogenesis of depression in a chronic unpredictable mild stress (CUMS) mouse model. We found that c-Fos expression in these VTA-projecting orexin neurons specifically decreased in CUMS-treated mice. Optogenetic and chemogenetic activation of orexin terminals in the VTA significantly reversed depressive behavior. Microinjection of orexin-A, but not orexin-B, into the VTA significantly improved depressive-like behavior. Our study provided direct evidence that the VTA orexinergic afferents participate in the mechanism of depression, and the orexin-1 receptor plays a major role.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b59ad5cdee123c15af2ced296e8c2f1cTest
https://doi.org/10.1016/j.bbrc.2021.09.062Test

9

Exploring the Role of Orexinergic Neurons in Parkinson’s Disease

المؤلفون: Saurabh Bhatia, Ahmed Al-Harassi, Neelam Sharma, Simona Bungau, Mohammed M Abdel-Daim, Aayush Sehgal, Sachin Kumar, Sukhbir Singh, Tapan Behl

المصدر: Neurotoxicity Research. 39:2141-2153

الوصف: Parkinson's disease (PD) is a neurodegenerative disease affecting about 2% of the population. A neuropeptide, orexin, is linked with sleep abnormalities in the parkinsonian patient. This study aimed to review the changes in the orexinergic system in parkinsonian subjects and the effects of orexin. A number of search techniques were used and presumed during the search, including cloud databank searches of PubMed and Medline using title words, keywords, and MeSH terms. PD is characterised by motor dysfunctions (postural instability, rigidity, tremor) and cognitive disorders, sleep-wake abnormalities grouped under non-motor disorders. The Orexinergic system found in the hypothalamus is linked with autonomic function, neuroprotection, learning and memory, and the sleep-wake cycle. Prepro-orexin, a precursor peptide (130 amino acids), gives rise to orexins (Orx-A and Orx-B). Serum orexin level measurement is vital for evaluating several neurological disorders (Alzheimer's disease, Huntington's disease, and PD). Orexinergic neurons are activated by hypoglycemia and ghrelin, while they are restrained by food consumption and leptin. Orexinergic system dysfunctioning was found to be linked with non-motor symptoms (sleep abnormalities) in PD. Orexinergic neuron's behaviour may be either inhibitory or excitatory depending on the environment in which they are present. As well, orexin antagonists are found to improve the abnormal sleep pattern. Since the orexinergic system plays a role in several psychological and neurological disorders, therefore, these disorders can be managed by targeting this system.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c3b272275d02a6d7fb2dffe688db08d2Test
https://doi.org/10.1007/s12640-021-00411-4Test

10

No loss of orexin/hypocretin, melanin‐concentrating hormone or locus coeruleus noradrenergic neurons in a rat model of chronic sleep restriction

المؤلفون: Andrew Baldin, Kazue Semba, Samuel Deurveilher, Michael Antonchuk, Brock St C Saumure

المصدر: European Journal of Neuroscience. 54:6027-6043

مصطلحات موضوعية: Adrenergic Neurons, Male, medicine.medical_specialty, Lateral hypothalamus, Melanin-concentrating hormone, chemical and pharmacologic phenomena, Stereology, Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Animals, Effects of sleep deprivation on cognitive performance, Rats, Wistar, Axon, 030304 developmental biology, Sleep restriction, Melanins, Orexins, 0303 health sciences, Hypothalamic Hormones, General Neuroscience, Rats, Orexin, Pituitary Hormones, medicine.anatomical_structure, Endocrinology, nervous system, chemistry, Locus coeruleus, Locus Coeruleus, Sleep, 030217 neurology & neurosurgery

الوصف: Chronic sleep restriction (CSR) is common in modern society, adversely affecting cognitive performance and health. Yet how it impacts neurons regulating sleep remains unclear. Several studies using mice reported substantial losses of wake-active orexin/hypocretin and locus coeruleus (LC) noradrenergic neurons, but not rapid eye movement sleep-active melanin-concentrating hormone (MCH) neurons, following CSR. Here, we used immunohistochemistry and stereology to examine orexin, MCH and LC noradrenergic neurons in a rat model of CSR that uses programmed wheel rotation (3 h on/1 h off; '3/1' protocol). Adult male Wistar rats underwent one or four cycles of the 4-day 3/1 CSR protocol, with 2-day recovery between cycles in home cages. Time-matched control rats were housed in locked wheels/home cages. We found no significant differences in the numbers of orexin, MCH and LC noradrenergic neurons following either one- or four-cycle CSR protocol compared to respective controls. Similarly, the four-cycle CSR protocol had no effect on the densities of orexin axon terminals in the LC, noradrenergic dendrites in the LC and noradrenergic axon terminals in the frontal cortex. Body weights, however, decreased after one cycle of CSR and then increased with diminishing slope over the next three cycles. Thus, we found no evidence for loss of orexin or LC noradrenergic neurons following one and four cycles of the 4-day 3/1 CSR protocol in rats. Differences in CSR protocols and/or possible species differences in neuronal vulnerability to sleep loss may account for the discrepancy between the current results in rats and previous findings in mice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a390e4b575be90b14537f4eab45f17bTest
https://doi.org/10.1111/ejn.15412Test

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