The Subthalamic Neurons are Activated by Both Orexin-A and Orexin-B

Sheng, Qing; Xue, Yan; Wang, Mengying; Chen, An-Qi; Liu, Cui; Liu, Yunhai; Chu, Huaqiang; Chen, Lei

doi:10.1016/j.neuroscience.2017.11.008

Cited by 16 publications

(12 citation statements)

References 60 publications

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“…For example, orexins excite the neurons of cerebellar interpositus nucleus ( Yu et al, 2010 ) and globus pallidus internus in rat ( Gao et al, 2017 ). Our previous study also revealed that orexins increase the firing rate of the subthalamic neurons ( Sheng et al, 2018 ) and globus pallidus neurons in rats ( Xue et al, 2016 ). All these findings indicate that orexin-A might be a potential target for the treatment of parkinsonian motor deficiency.…”

Section: Discussionmentioning

confidence: 77%

Orexin-A Exerts Neuroprotective Effects via OX1R in Parkinson’s Disease

et al. 2018

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Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive and selective death of dopaminergic neurons. Orexin-A is involved in many biological effects of the body. It has been reported that orexin-A has protective effects in cellular models of PD. However, little is known about the protective effects of orexin-A in animal parkinsonian models and the cellular mechanism has not yet been fully clarified. The aim of this study was to evaluate the effects of orexin-A in MPTP mice model of PD as well as the possible neuroprotective mechanisms of orexin-A on dopaminergic neurons. The results from animal experiments demonstrated that orexin-A attenuated the loss of dopaminergic neurons and the decrease of tyrosine hydroxylase (TH) expression in the substantia nigra, normalized the striatal dopaminergic fibers, and prevented the depletion of dopamine and its metabolites in the striatum. MPTP-treated mice showed cognitive impairments accompanied with significant motor deficiency. Orexin-A improved MPTP-induced impairments in both motor activity and spatial memory. Importantly, orexin-A increased the protein level of brain-derived neurotrophic factor (BDNF) in dopaminergic neurons of the substantia nigra. Furthermore, the protective effects of orexin-A on MPTP parkinsonian mice could be blocked by orexinergic receptor 1 (OX1R) antagonist, SB334867. In another set of experiments with SH-SY5Y dopaminergic cells, orexin-A significantly induced the expression of BDNF in a dose and time-dependent manner. The upregulation of BDNF is mainly concerned with PI3K and PKC signaling pathways via OX1R. The present study demonstrated that orexin-A exerted neuroprotective effects on MPTP parkinsonian mice, which may imply orexin-A as a potential therapeutic target for PD.

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Section: Discussionmentioning

confidence: 77%

Orexin-A Exerts Neuroprotective Effects via OX1R in Parkinson’s Disease

et al. 2018

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“…Previous studies indicated that endogenous orexins regulate the firing activities of subthalamic neurons (Sheng et al . ), hippocampal CA1 neurons (Chen et al . ), and globus pallidus neurons (Xue et al .…”

Section: Discussionmentioning

confidence: 99%

Orexins increase the firing activity of nigral dopaminergic neurons and participate in motor control in rats

Liu

Xue

Liu

et al. 2018

Journal of Neurochemistry

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Orexin is a member of neuropeptides which is involved in the central motor control. The substantia nigra pars compacta (SNc) is an important nucleus participating in motor control under both physiological and pathological conditions. Morphological studies reveal that orexinergic neurons located in lateral hypothalamus innervate the SNc. Both orexin-1 receptors (OX R) and orexin-2 receptors (OX R) are expressed in the SNc. To investigate the effects of orexins on SNc, single unit in vivo extracellular recordings and behavioral tests were performed in this study. Micro-pressure administration of orexin A and orexin B significantly increased the spontaneous firing rate of nigral DAergic neurons by 65.87 ± 7.73% and 90.49 ± 17.83%, respectively. The excitatory effects of orexin A on nigral DAergic neurons were mainly mediated by OX R, while OX R were involved in the increase in firing rate induced by orexin B. Selectively blocking OX R and OX R significantly decreased the firing rate of nigral DAergic neurons by 36.77 ± 6.26% and 32.04 ± 6.12%, respectively, which suggested that endogenous orexins modulated the spontaneous firing activity of nigral DAergic neurons. Finally, both elevated body swing test and haloperidol-induced postural behavioral test showed that unilateral microinjection of orexin A and orexin B induced significantly contralateral-biased swing and deflection behavior. Meanwhile, the specific OX R and OX R antagonists produced opposite effects. The present electrophysiological and behavioral studies suggested that orexins increased the firing activity of nigral DAergic neurons and participated in central motor control. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

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“…The upregulation of BDNF is mainly via OX1R. [ 68 ] Long-term therapy with ropinirole in PD leads to significant reduction in the orexin activity which might explain the adverse effect of ropinirole-induced sleep disorder through inhibition of glutamaterigic excitatory effect on the orexinergic neurons. Therefore, pharmacotherapy of PD should be re-evaluated in this context.…”

Section: Role Of Orexin In Neurodegenerative Diseasesmentioning

confidence: 99%

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review

et al. 2020

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Orexin is a neuropeptide secreted from lateral hypothalamus and pre-frontal cortex concerned in the wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words during the search. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of monoaminergic system, which affect cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotropin and corticosteroid secretions via activation of central corticotropin-releasing hormone. Cerebrospinal fluid (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin serum levels are reduced Parkinson disease, Alzheimer dementia, Huntington's disease, amyotrphic lateral sclerosis, and multiple sclerosis. Orexin antagonist leads to significant reduction of sympathetic over-activity during withdrawal syndrome. As well, orexin antagonist improves sleep pattern. Orexinergic system is involved in the different psychiatric and neurological disorders; therefore, targeting of this system could be possible novel pathway in the management of these disorders. In addition, measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients.

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The Subthalamic Neurons are Activated by Both Orexin-A and Orexin-B

Cited by 16 publications

References 60 publications

Orexin-A Exerts Neuroprotective Effects via OX1R in Parkinson’s Disease

Orexin-A Exerts Neuroprotective Effects via OX1R in Parkinson’s Disease

Orexins increase the firing activity of nigral dopaminergic neurons and participate in motor control in rats

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review

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