Progressive changes of orexin system in a rat model of 6-hydroxydopamineinduced Parkinson’s disease

Cui, Long‐Biao; Li, Bowei; Jin, Xiaohang; Zhao, Lin; Shi, Juan

doi:10.1007/s12264-010-0410-9

Cited by 30 publications

(10 citation statements)

References 16 publications

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“…The orexin system develops very early in vivo (Van den Pol et al 2001 ; Stoyanova et al 2010 ); therefore the early expression of OR1 which we observed already at 1 DIV could be another indication for the importance of orexinergic input in developing networks. This observation is in accordance with the findings that the human sleep disorder, narcolepsy, as well as different neurodegenerative diseases, were recently related to a massive reduction or deficit of orexins and their receptors and a decreased level of OXA in the cerebrospinal fluid (Cui et al 2010 ; Friedman et al 2007 ; Petersén et al 2005 ; Ripley et al 2001 ). Experiments with transient common carotid artery occlusion in mice demonstrated increased levels of OXA and OR1 after ischemia (Nakamachi et al 2005 ).…”

Section: Discussionsupporting

confidence: 90%

Orexin A in Cortical Cultures: Expression and Effect on Synaptogenesis During Development

2011

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Orexin A (OXA) is an excitatory hypothalamic neurotransmitter and ligand for Orexin Receptor-1 (OR1), isolated from a small group of hypothalamic neurons. OXA orchestrates different brain functions, and at the cognitive level some of the effects of insufficiency of OXA are well-known, for example in Parkinson’s disease. It is widely assumed that deteriorated cognitive processes are related to impaired network connectivity. However, little is known about the effects of OXA in network connectivity and synaptogenesis. Therefore, to obtain insight into this problem we designed experiments with two groups of networks of dissociated cortical neurons: one group incubated in a plain medium and another chronically treated with OXA. After 1, 2, 3 or 4 weeks in vitro we applied immunocytochemistry for detection of OXA, OR1, and synaptic marker synaptophysin. Shortly after plating, 91 ± 8% of the neurons cultivated in a plain medium expressed OXA-immunoreactivity, which does normally not occur in vivo indicating that neurons may change their phenotype under non-natural culture conditions to develop synaptically coupled networks. The fraction of orexinergic neurons decreased to 33 ± 21% after 4 weeks in vitro. OXA expression was highest in the first week of network formation, the period of maximum synaptogenesis, and then decreased and stabilized in the weeks thereafter. Our hypothesis that OXA plays a role in the network development as a synaptogenic factor was supported by higher levels, earlier onset, and sustained increase of synaptophysin expression in experiments with chronic OXA application to the culture medium.

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Section: Discussionsupporting

confidence: 90%

Orexin A in Cortical Cultures: Expression and Effect on Synaptogenesis During Development

2011

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“…It was reported that parkinsonian patients display significant loss of orexinergic neurons in post-mortem exams ( Fronczek et al, 2007 ; Thannickal et al, 2007 ). Experiments with 6-hydroxydopamine (6-OHDA)-induced rat model of PD revealed that the number of orexinergic neurons in the lateral hypothalamus decreases significantly ( Cui et al, 2010 ). Furthermore, the orexin levels in plasma and cerebrospinal fluid decrease dramatically in parkinsonian patients ( Drouot et al, 2003 ; Fronczek et al, 2007 ; Thannickal et al, 2007 ; Baumann et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

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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“…Further studies in rats showed that injection of 6-OHDA in the DS or MFB decreases the number of orexin neurons in the LH (Cui et al, 2010; Oliveira et al, 2018), thereby reproducing a similar damage described in PD (Maeda et al, 2006; Thannickal et al, 2007). This loss was paralleled by reduced baseline respiratory frequency during sleep in the light-on period (Oliveira et al, 2018), a condition reminiscent of breathing disturbances and sleep apnea observed in PD patients (Mery et al, 2017; Videnovic, 2017).…”

Section: Introductionmentioning

confidence: 56%

“…Combined loss of dopamine, noradrenaline, and to some extent functional inactivation of serotonin has been achieved with neurotoxins (Breese and Traylor, 1971; Reader and Gauthier, 1984; Santiago et al, 2010; Bonito-Oliva et al, 2013). In addition, 6-OHDA has been found to reduce the number of orexin/hypocretin neurons in the LH (Cui et al, 2010; Oliveira et al, 2018). Therefore, some of the sleep abnormalities observed in rodent models of PD may depend on the loss, or impairment, of one or more of these components of the arousal system.…”

Section: Discussionmentioning

confidence: 99%

Sleep Disorders in Rodent Models of Parkinson’s Disease

et al. 2019

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Sleep disorders are frequently diagnosed in Parkinson’s disease and manifested in the prodromal and advanced stages of the disease. These conditions, which in some cases affect more than 50% of Parkinson’s disease (PD) patients, include hypersomnia, often manifested as excessive daytime sleepiness, insomnia, characterized by delayed initiation and fragmentation of sleep at night, and disruption of rapid eye movement (REM) sleep, resulting in loss of atonia and dream enactment. Standard dopamine replacement therapies for the treatment of motor symptoms are generally inadequate to combat sleep abnormalities, which seriously affect the quality of life of PD patients. Rodent models still represent a major tool for the study of many aspects of PD. They have been primarily designed to eliminate midbrain dopamine neurons and elicit motor impairment, which are the traditional pathological features of PD. However, rodent models are increasingly employed to investigate non-motor symptoms, which are often caused by degenerative processes affecting multiple monoaminergic and peptidergic structures. This review describes how neurotoxic and genetic manipulations of rats and mice have been utilized to reproduce some of the major sleep disturbances associated with PD and to what extent these abnormalities can be linked to nondopaminergic dysfunction, affecting for instance noradrenaline, serotonin, and orexin transmission. Strengths and limitations are discussed, as well as the consistency of results obtained so far, and the need for models that better reproduce the multisystemic neurodegenerative nature of PD, thereby allowing to replicate the complex etiology of sleep-related disorders.

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Progressive changes of orexin system in a rat model of 6-hydroxydopamineinduced Parkinson’s disease

Cited by 30 publications

References 16 publications

Orexin A in Cortical Cultures: Expression and Effect on Synaptogenesis During Development

Orexin A in Cortical Cultures: Expression and Effect on Synaptogenesis During Development

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

Sleep Disorders in Rodent Models of Parkinson’s Disease

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