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

Stoyanova, Irina; Rutten, Wim; Feber, Joost le

doi:10.1007/s10571-011-9733-y

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…Consistent with this finding our results and published experimental studies [34, 53] show that ischemic stroke induces increased expression of Ox1R in the brain, which correlates with decreases of OXA in cerebrospinal fluid as an adaptive response to maintain OXA supply to the brain. Finally, a recent study showed that in some conditions such ischemic stroke, cortical neurons may homeostatically switch to the production of OXA as an adaptation mechanism [54]. This observation is consistent with the notion that re-mapping processes that spontaneously occur after stroke [55, 56] may induce an early change of genes expression, and OX and MCH systems may be involved in this process.…”

Section: Discussionsupporting

confidence: 80%

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

et al. 2017

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Study ObjectivesSleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke.MethodsSprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.ResultsA reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.ConclusionsOur data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

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Section: Discussionsupporting

confidence: 80%

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

et al. 2017

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“…Importantly, intravenous or intranasal administration of orexin-A to non-human primates rescues cognitive impairments due to sleep-deprivation ( Deadwyler et al, 2007 ). The protection of orexin-A on cognition is considered to be relevant with enhancing long-term potentiation ( Wayner et al, 2004 ; Akbari et al, 2008 , 2011 ), and positively related to the neurogenesis and synaptic plasticity in hippocampus ( Stoyanova et al, 2010 , 2012 ; Yang et al, 2013 ; Zhao et al, 2014 ). In present study, we demonstrated that chronic i.c.v.…”

Section: Discussionmentioning

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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“…In addition, orexins promote synaptogenesis, network development, and maturation. In cultures of cortical neurons, orexin A acts as synaptogenic factor promoting neural interactions [Stoyanova et al, 2012]. Although the detailed molecular mechanism remains to be elucidated, the indirect upregulation of neurotrophic factors like neurotrophin-3 could explain this action [Yamada et al, 2009].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these 'classical' functions, orexins have been proposed as important signaling molecules during brain development and maturation, being related to synaptogenesis and neuroprotection Stoyanova et al, 2010Stoyanova et al, , 2012. In contrast with the relatively abundant literature on orexins in the adult brain, there are few studies about the role of these neuropeptides in the developing brain of vertebrates.…”

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confidence: 99%

Spatiotemporal Development of the Orexinergic (Hypocretinergic) System in the Central Nervous System of <b><i>Xenopus laevis</i></b>

López¹,

Morales²,

González³

2016

Brain Behav Evol

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The present immunohistochemical study represents a detailed spatiotemporal analysis of the localization of orexin-immunoreactive (OX-ir) cells and fibers throughout development in the brain of the anuran amphibian Xenopus laevis, a model frequently used in developmental studies. Anurans undergo remarkable physiological changes during the early life stages, and very little is known about the ontogeny and the localization of the centers that control functions such as appetite and feed ingestion in the developing brain. We examined the onset of the orexinergic system, demonstrated to be involved in appetite regulation, using antibodies against mammalian orexin-A and orexin-B peptides. Simultaneous detection of orexins with other territorial markers was used to assess the precise location of the orexinergic cells in the hypothalamus, analyzed within a segmental paradigm. Double staining of orexins and tyrosine hydroxylase served to evaluate possible interactions with the catecholaminergic systems. At early embryonic stages, the first OX-ir cells were detected in the hypothalamus and, soon after, long descending projections were observed through the brainstem to the spinal cord. As brain development proceeded, the double-staining techniques demonstrated that this OX-ir cell group was located in the suprachiasmatic nucleus within the alar hypothalamus. Throughout larval development, the number of OX-ir cells increased notably and a widespread fiber network that innervated the main areas of the forebrain and brainstem was progressively formed, including innervation in the posterior tubercle and mesencephalon, the locus coeruleus, and the nucleus of the solitary tract where catecholaminergic cells are present. In addition, orexinergic cells were detected in the preoptic area and the tuberal hypothalamus only at late prometamorphic stages. The final distribution pattern, largely similar to that of the adult, was achieved through metamorphic climax. The early expression of orexins in Xenopus suggests important roles in brain development in the embryonic period before feeding, and the progression of the temporal and spatial complexity of the orexinergic system might be correlated to the maturation of appetite control regulation, among other functions.

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

Cited by 7 publications

References 41 publications

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

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

Spatiotemporal Development of the Orexinergic (Hypocretinergic) System in the Central Nervous System of <b><i>Xenopus laevis</i></b>

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