河南中医药大学第一临床医学院/河南中医药大学第一附属医院脑病中心,郑州 450000
Received:16 October 2023,
Revised:2024-08-03,
Accepted:08 September 2024,
Published:28 November 2024
移动端阅览
邹旭欢,兰瑞,王玮玮,等.下丘脑食欲素参与帕金森病神经保护作用的研究进展[J].重庆医科大学学报,2024,49(11):1350-1355.
Zou Xuhuan,Lan Rui,Wang Weiwei,et al.Research progress on the neuroprotective effect of hypothalamic orexin in Parkinson’s disease[J].Journal of Chongqing Medical University,2024,49(11):1350-1355.
邹旭欢,兰瑞,王玮玮,等.下丘脑食欲素参与帕金森病神经保护作用的研究进展[J].重庆医科大学学报,2024,49(11):1350-1355. DOI: 10.13406/j.cnki.cyxb.003611.
Zou Xuhuan,Lan Rui,Wang Weiwei,et al.Research progress on the neuroprotective effect of hypothalamic orexin in Parkinson’s disease[J].Journal of Chongqing Medical University,2024,49(11):1350-1355. DOI: 10.13406/j.cnki.cyxb.003611.
食欲素是下丘脑分泌的重要神经肽,参与多种大脑活动。帕金森病是常见的神经退行性疾病,其发生与黑质致密部中的多巴胺神经元进行性丧失、下丘脑中路易小体的形成相关。研究发现食欲素系统通过直接作用于大量多巴胺神经元所在的腹侧被盖区内的食欲素受体来调节多巴胺功能,而多巴胺也参与到食欲素神经元的电生理活动调节中。文中探讨了下丘脑食欲素系统对帕金森病的神经保护作用,并从食欲素对帕金森病的运动症状、非运动症状的作用和机制作简要综述。
Orexin is an important neuropeptide secreted by the hypothalamus and participates in a variety of brain activities. Parkinson’s disease is a common neurodegenerative disease,and its occurrence is related to the progressive loss of dopamine neurons in the substantia nigra pars compacta and the formation of Lewy bodies in the hypothalamus. Previous studies found that the orexin system regulates dopamine function by directly acting on the orexin receptor in the ventral tegmental area where a large number of dopaminergic neurons are located. Additionally,dopamine participates in the regulation of the electrophysiological activity of orexin neurons. This paper discusses the neuroprotective effect of hypothalamic orexin system in Parkinson’s disease,and briefly summarizes the effects and mechanisms of orexin on motor and non-motor symptoms of Parkinson’s disease.
Toor B , Ray LB , Pozzobon A , et al . Sleep,orexin and cognition [J ] . Front Neurol Neurosci , 2021 , 45 : 38 - 51 .
Sackner-Bernstein J . Estimates of intracellular dopamine in Parkinson’s disease:a systematic review and meta-analysis [J ] . J Parkinsons Dis , 2021 , 11 ( 3 ): 1011 - 1018 .
Pennington C , Duncan G , Ritchie C . Altered awareness of cognitive and neuropsychiatric symptoms in Parkinson’s disease and Dementia with Lewy Bodies:a systematic review [J ] . Int J Geriatr Psychiatry , 2021 , 36 ( 1 ): 15 - 30 .
Sakurai T , Amemiya A , Ishii M , et al . Orexins and orexin receptors:a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior [J ] . Cell , 1998 , 92 ( 5 ): 696 .
de Lecea L , Kilduff TS , Peyron C , et al . The hypocretins:hypothalamus-specific peptides with neuroexcitatory activity [J ] . Proc Natl Acad Sci U S A , 1998 , 95 ( 1 ): 322 - 327 .
Couvineau A , Voisin T , Nicole P , et al . Orexins as novel therapeutic targets in inflammatory and neurodegenerative diseases [J ] . Front Endocrinol , 2019 , 10 : 709 .
Liu C , Xue Y , Liu MF , et al . Orexins increase the firing activity of nigral dopaminergic neurons and participate in motor control in rats [J ] . J Neurochem , 2018 , 147 ( 3 ): 380 - 394 .
Xu TR , Yang Y , Ward R , et al . Orexin receptors:multi-functional therapeutic targets for sleeping disorders,eating disorders,drug addiction,cancers and other physiological disorders [J ] . Cell Signal , 2013 , 25 ( 12 ): 2413 - 2423 .
Sellayah D , Sikder D . Orexin restores aging-related brown adipose tissue dysfunction in male mice [J ] . Endocrinology , 2014 , 155 ( 2 ): 485 - 501 .
Jin JH , Chen QH , Qiao QC , et al . Orexin neurons in the lateral hypothalamus project to the medial prefrontal cortex with a rostro-caudal gradient [J ] . Neurosci Lett , 2016 , 621 : 9 - 14 .
Brodnik ZD , Alonso IP , Xu W , et al . Hypocretin receptor 1 involvement in cocaine-associated behavior:therapeutic potential and novel mechanistic insights [J ] . Brain Res , 2020 , 1731 : 145894 .
Morales-Mulia S , Magdaleno-Madrigal VM , Nicolini H , et al . Orexin-a up-regulates dopamine D2 receptor and mRNA in the nucleus accumbens shell [J ] . Mol Biol Rep , 2020 , 47 ( 12 ): 9689 - 9697 .
Li J , Li H , Wang D , et al . Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats [J ] . Br J Anaesth , 2019 , 123 ( 4 ): 497 - 505 .
Quarta D , Smolders I. Rewarding , reinforcing and incentive salient events involve orexigenic hypothalamic neuropeptides regulating mesolimbic dopaminergic neurotransmission [J ] . Eur J Pharm Sci , 2014 , 57 : 2 - 10 .
Prince CD , Rau AR , Yorgason JT , et al . Hypocretin/Orexin regulation of dopamine signaling and cocaine self-administration is mediated predominantly by hypocretin receptor 1 [J ] . ACS Chem Neurosci , 2015 , 6 ( 1 ): 138 - 146 .
Korotkova TM , Eriksson KS , Haas HL , et al . Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro [J ] . Regul Pept , 2002 , 104 ( 1/2/3 ): 83 - 89 .
Li Y , van den Pol AN . Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons [J ] . J Neurosci , 2005 , 25 ( 1 ): 173 - 183 .
Yamanaka A , Muraki Y , Ichiki K , et al . Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner [J ] . J Neurophysiol , 2006 , 96 ( 1 ): 284 - 298 .
Alberto CO , Trask RB , Quinlan ME , et al . Bidirectional dopaminergic modulation of excitatory synaptic transmission in orexin neurons [J ] . J Neurosci , 2006 , 26 ( 39 ): 10043 - 10050 .
Bubser M , Fadel JR , Jackson LL , et al . Dopaminergic regulation of orexin neurons [J ] . Eur J Neurosci , 2005 , 21 ( 11 ): 2993 - 3001 .
Hu B , Yang N , Qiao QC , et al . Roles of the orexin system in central motor control [J ] . Neurosci Biobehav Rev , 2015 , 49 : 43 - 54 .
Wang Y , Chen AQ , Xue Y , et al . Orexins alleviate motor deficits via increasing firing activity of pallidal neurons in a mouse model of Parkinson’s disease [J ] . Am J Physiol Cell Physiol , 2019 , 317 ( 4 ): 800 - 812 .
Liu MF , Xue Y , Liu C , et al . Orexin-a exerts neuroprotective effects via OX1R in Parkinson’s disease [J ] . Front Neurosci , 2018 , 12 : 835 .
Xue Y , Yang YT , Liu HY , et al . Orexin-a increases the activity of globus pallidus neurons in both normal and parkinsonian rats [J ] . Eur J Neurosci , 2016 , 44 ( 5 ): 2247 - 2257 .
Hadadianpour Z , Fatehi F , Ayoobi F , et al . The effect of orexin-A on motor and cognitive functions in a rat model of Parkinson’s disease [J ] . Neurol Res , 2017 , 39 ( 9 ): 845 - 851 .
Pokusa M , Hajduchova D , Buday T , et al . Respiratory function and dysfunction in parkinson-type neurodegeneration [J ] . Physiol Res , 2020 , 69 ( Suppl 1 ): S69 - S79 .
Guilherme EM , de Fátima Carreira Moreira R , de Oliveira A , et al . Respiratory disorders in Parkinson’s disease [J ] . J Parkinsons Dis , 2021 , 11 ( 3 ): 993 - 1010 .
Oliveira LM , Falquetto B , Moreira TS , et al . Orexinergic neurons are involved in the chemosensory control of breathing during the dark phase in a Parkinson’s disease model [J ] . Exp Neurol , 2018 , 309 : 107 - 118 .
Ferrer I , López-Gonzalez I , Carmona M , et al . Neurochemistry and the non-motor aspects of PD [J ] . Neurobiol Dis , 2012 , 46 ( 3 ): 508 - 526 .
Suzuki K , Miyamoto M , Miyamoto T , et al . Sleep disturbances associated with Parkinson’s disease [J ] . Parkinsons Dis , 2011 , 2011 : 219056 .
Bridoux A , Moutereau S , Covali-Noroc A , et al . Ventricular orexin-A(hypocretin-1) levels correlate with rapid-eye-movement sleep without atonia in Parkinson’s disease [J ] . Nat Sci Sleep , 2013 , 5 : 87 - 91 .
Yuan Y , Zhang YM , Cheng YY , et al . Cerebrospinal fluid TNF-α and orexin in patients with Parkinson’s disease and rapid eye movement sleep behavior disorder [J ] . Front Neurol , 2022 , 13 : 826013 .
Sakurai T . Orexin deficiency and narcolepsy [J ] . Curr Opin Neurobiol , 2013 , 23 ( 5 ): 760 - 766 .
Ogawa T , Kajiyama Y , Ishido H , et al . Decreased cerebrospinal fluid orexin levels not associated with clinical sleep disturbance in Parkinson’s disease:a retrospective study [J ] . PLoS One , 2022 , 17 ( 12 ): e0279747 .
Aitta-Aho T , Pappa E , Burdakov D , et al . Cellular activation of hypothalamic hypocretin/orexin neurons facilitates short-term spatial memory in mice [J ] . Neurobiol Learn Mem , 2016 , 136 : 183 - 188 .
Stanojlovic M , Jr Pallais Yllescas JP , Vijayakumar A , et al . Early sociability and social memory impairment in the A53T mouse model of Parkinson’s disease are ameliorated by chemogenetic modulation of orexin neuron activity [J ] . Mol Neurobiol , 2019 , 56 ( 12 ): 8435 - 8450 .
Oliveira LM , Henrique E , Bustelli IB , et al . Depletion of hypothalamic hypocretin/orexin neurons correlates with impaired memory in a Parkinson’s disease animal model [J ] . Exp Neurol , 2020 , 323 : 113110 .
Zheng LF , Wang ZY , Li XF , et al . Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson’s disease [J ] . Brain Res , 2011 , 1420 : 59 - 67 .
Yang YL , Ran XR , Li Y , et al . Expression of dopamine receptors in the lateral hypothalamic nucleus and their potential regulation of gastric motility in rats with lesions of bilateral substantia nigra [J ] . Front Neurosci , 2019 , 13 : 195 .
Vernier P , Moret F , Callier S , et al . The degeneration of dopamine neurons in Parkinson’s disease:insights from embryology and evolution of the mesostriatocortical system [J ] . Ann N Y Acad Sci , 2004 , 1035 : 231 - 249 .
Douhou A , Troadec JD , Ruberg M , et al . Survival promotion of mesencephalic dopaminergic neurons by depolarizing concentrations of K + requires concurrent inactivation of NMDA or AMPA/kainate receptors [J ] . J Neurochem , 2001 , 78 ( 1 ): 163 - 174 .
Hrabovszky E , Molnár CS , Borsay BÁ , et al . Orexinergic input to dopaminergic neurons of the human ventral tegmental area [J ] . PLoS One , 2013 , 8 ( 12 ): e83029 .
Bensaid M , Tandé D , Fabre V , et al . Sparing of orexin-A and orexin-B neurons in the hypothalamus and of orexin fibers in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques [J ] . Eur J Neurosci , 2015 , 41 ( 1 ): 129 - 136 .
Schmitt O , Usunoff KG , Lazarov NE , et al . Orexinergic innervation of the extended amygdala and basal Ganglia in the rat [J ] . Brain Struct Funct , 2012 , 217 ( 2 ): 233 - 256 .
Chemelli RM , Willie JT , Sinton CM , et al . Narcolepsy in orexin knockout mice:molecular genetics of sleep regulation [J ] . Cell , 1999 , 98 ( 4 ): 437 - 451 .
Kiwaki K , Kotz CM , Wang CF , et al . Orexin A(hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats [J ] . Am J Physiol Endocrinol Metab , 2004 , 286 ( 4 ): 551 - 559 .
Kotz CM , Wang C , Teske JA , et al . Orexin A mediation of time spent moving in rats:neural mechanisms [J ] . Neuroscience , 2006 , 142 ( 1 ): 29 - 36 .
Pagnussat AS , Kleiner AFR , Rieder CRM , et al . Plantar stimulation in parkinsonians:from biomarkers to mobility-randomized-controlled trial [J ] . Restor Neurol Neurosci , 2018 , 36 ( 2 ): 195 - 205 .
Cagni FC , Campêlo CLDC , Coimbra DG , et al . Association of BDNF Val66MET polymorphism with Parkinson’s disease and depression and anxiety symptoms [J ] . J Neuropsychiatry Clin Neurosci , 2017 , 29 ( 2 ): 142 - 147 .
Scalzo P , Kümmer A , Bretas TL , et al . Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson’s disease [J ] . J Neurol , 2010 , 257 ( 4 ): 540 - 545 .
Park H , Poo MM . Neurotrophin regulation of neural circuit development and function [J ] . Nat Rev Neurosci , 2013 , 14 ( 1 ): 7 - 23 .
Wang Y , Liu H , Du XD , et al . Association of low serum BDNF with depression in patients with Parkinson’s disease [J ] . Parkinsonism Relat Disord , 2017 , 41 : 73 - 78 .
Berhe DF , Gebre AK , Assefa BT . Orexins role in neurodegenerative diseases:from pathogenesis to treatment [J ] . Pharmacol Biochem Behav , 2020 , 194 : 172929 .
Kierans SJ , Taylor CT . Regulation of glycolysis by the hypoxia-inducible factor(HIF):implications for cellular physiology [J ] . J Physiol , 2021 , 599 ( 1 ): 23 - 37 .
Palikaras K , Lionaki E , Tavernarakis N . Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis [J ] . Cell Death Differ , 2015 , 22 ( 9 ): 1399 - 1401 .
Rani L , Mondal AC . Emerging concepts of mitochondrial dysfunction in Parkinson’s disease progression:pathogenic and therapeutic implications [J ] . Mitochondrion , 2020 , 50 : 25 - 34 .
Mamelak M . Parkinson’s disease,the dopaminergic neuron and gammahydroxybutyrate [J ] . Neurol Ther , 2018 , 7 ( 1 ): 5 - 11 .
Feng Y , Liu T , Li XQ , et al . Neuroprotection by Orexin-a via HIF-1α induction in a cellular model of Parkinson’s disease [J ] . Neurosci Lett , 2014 , 579 : 35 - 40 .
Pasban-Aliabadi H , Esmaeili-Mahani S , Abbasnejad M . Orexin-a protects human neuroblastoma SH-SY5Y cells against 6-hydroxydo-pamine-induced neurotoxicity:involvement of PKC and PI3K signaling pathways [J ] . Rejuvenation Res , 2017 , 20 ( 2 ): 125 - 133 .
0
Views
12
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621
