Orexin knockout mice exhibit impaired spatial working memory

Dang, Ruozhi; Chen, Qiuhan; Song, Jie; He, Chao; Zhang, Jun; Xia, Jianxia; Hu, Zhian

doi:10.1016/j.neulet.2018.01.013

Cited by 29 publications

(13 citation statements)

References 24 publications

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“…Recent studies have suggested that orexins are involved in learning and memory processes. Orexin-deficient mice exhibit impairments in spatial working memory ( Dang et al, 2018 ) and two-way active avoidance memory ( Mavanji et al, 2017 ), while orexin-A replacement restores the cognitive impairment ( Mavanji et al, 2017 ). Furthermore, orexin-A enhances hippocampal neurogenesis and attenuates memory deficits in rats with hippocampal atrophy induced by pentylenetetrazol ( Zhao et al, 2014 ).…”

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…Using chemogenetics, one study in mice found that increasing OX neuron activity improved short-term memory for a novel spatial location, assessed through a delayed spontaneous alternation T-maze test for a food reward (Aitta-Aho et al 2016). Conversely, another study found that OX knockout mice were less successful than control mice in this same task (Dang et al 2018). Moreover, this effect of OX on memory appears to be specific for spatial memory, as OX neuron activation did not affect performance in a non-food baited object recognition task (Aitta-Aho et al 2016).…”

Section: Orexin/hypocretin and Spatial Memory For Foodmentioning

confidence: 95%

Orexin/hypocretin and dysregulated eating: Promotion of foraging behavior

Barson

2020

Brain Research

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At its discovery, orexin/hypocretin (OX) was hypothesized to promote food intake. Subsequently, with the identification of the participation of OX in numerous other phenomena, including arousal and drug seeking, this neuropeptide was proposed to be involved in highly motivated behaviors. The present review develops the hypothesis that the primary evolutionary function of OX is to promote foraging behavior, seeking for food under conditions of limited availability. Thus, it will first describe published literature on OX and homeostatic food intake, which shows that OX neurons are activated by conditions of food deprivation and in turn stimulate food intake. Next, it will present literature on excessive and binge-like food intake, which demonstrates that OX stimulates both intake and willingness to work for palatable food. Importantly, studies show that binge-like eating can be inhibited by OX antagonists at doses far lower than those required to suppress homeostatic intake (3 mg/kg vs. 30 mg/kg), suggesting that an OX-based pharmacotherapy, at the right dose, could specifically control dysregulated eating. Finally, the review will discuss the role of OX in foraging behavior, citing literature which shows that OX neurons, which are activated during the anticipation of food reward, can promote a number of phenomena involved in successful foraging, including food-anticipatory locomotor behavior, olfactory sensitivity, visual attention, spatial memory, and mastication. Thus, OX may promote homeostatic eating, as well as binge eating of palatable food, due to its ability to stimulate and coordinate the activities involved in foraging behavior.

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“…The actions of orexins probably influence also memory functions. Dang et al recently discovered that orexin knockout mice have impaired spatial memory [ 46 ]. Mavanji et al proved in a series of experiments that orexin-deficient mice develop memory impairments, which may be successfully treated with orexin supplementation, e.g., intra-hippocampal infusion [ 47 ].…”

Section: Mighty Transmitter—the Roles Of Orexinsmentioning

confidence: 99%

Orexins, Sleep, and Blood Pressure

2018

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Purpose of ReviewThe aim of this review was to summarize collected data on the role of orexin and orexin neurons in the control of sleep and blood pressure.Recent FindingsAlthough orexins (hypocretins) have been known for only 20 years, an impressive amount of data is now available regarding their physiological role. Hypothalamic orexin neurons are responsible for the control of food intake and energy expenditure, motivation, circadian rhythm of sleep and wake, memory, cognitive functions, and the cardiovascular system. Multiple studies show that orexinergic stimulation results in increased blood pressure and heart rate and that this effect may be efficiently attenuated by orexinergic antagonism. Increased activity of orexinergic neurons is also observed in animal models of hypertension.SummaryPharmacological intervention in the orexinergic system is now one of the therapeutic possibilities in insomnia. Although the role of orexin in the control of blood pressure is well described, we are still lacking clinical evidence that this is a possibility for a new approach in the treatment of cardiovascular diseases.

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Orexin knockout mice exhibit impaired spatial working memory

Cited by 29 publications

References 24 publications

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

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

Orexin/hypocretin and dysregulated eating: Promotion of foraging behavior

Orexins, Sleep, and Blood Pressure

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