Orexin neuropeptides modulate the hippocampal-dependent memory through basolateral amygdala interconnections

Abounoori, Mahdi; Maddah, Mohammad Moein; Ardeshiri, Motahareh Rouhi

doi:10.1016/j.cccb.2021.100035

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…As also reported above, orexin has a significant influence on arousal and wakefulness [40], as well as on attention (the ability to focus on specific stimuli while filtering out irrelevant information) [41]. Learning and memory are fundamental cognitive functions essential for acquiring and retaining new information; orexin may influence these processes through its enhancing effects on synaptic plasticity [42]. However, the exact mechanisms of orexin's impact on cognitive function certainly require further investigation, also for their potential implications for developing novel therapeutic strategies targeting cognitive dysfunction in CNS disorders.…”

Section: Cognitive Functionmentioning

confidence: 80%

Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite

Mogavero,

Godos,

Grosso

et al. 2023

Nutrients

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Orexin plays a significant role in the modulation of REM sleep, as well as in the regulation of appetite and feeding. This review explores, first, the current evidence on the role of orexin in the modulation of sleep and wakefulness and highlights that orexin should be considered essentially as a neurotransmitter inhibiting REM sleep and, to a much lesser extent, a wake promoting agent. Subsequently, the relationship between orexin, REM sleep, and appetite regulation is examined in detail, shedding light on their interconnected nature in both physiological conditions and diseases (such as narcolepsy, sleep-related eating disorder, idiopathic hypersomnia, and night eating syndrome). Understanding the intricate relationship between orexin, REM sleep, and appetite regulation is vital for unraveling the complex mechanisms underlying sleep-wake patterns and metabolic control. Further research in this field is encouraged in order to pave the way for novel therapeutic approaches to sleep disorders and metabolic conditions associated with orexin dysregulation.

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Section: Cognitive Functionmentioning

confidence: 80%

Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite

Mogavero,

Godos,

Grosso

et al. 2023

Nutrients

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“…The orexin system has drawn much attention during the last decade, especially after the launching of orexin receptor antagonists in clinical practice [ 9 , 12 , 19 , 38 , 39 , 40 , 41 ]. From a developmental point of view, it is interesting that invertebrates seem to have no orexin-like sequences and in non-mammalian vertebrates, only OX2R have been identified.…”

Section: Discussionmentioning

confidence: 99%

“…For example, throughout the rat brain, orexinergic axons and orexin receptors have been found to be widely distributed in several different areas [ 12 , 19 ]. Regarding the importance of the orexin system, the initially restricted correlation of orexin function with appetite control has gradually evolved to include sleep/wakefulness cycle regulation, and lately has been shown to have strong interactions with most functions of the autonomic and limbic systems [ 41 , 42 , 43 ]. In several species, the importance of orexins has been demonstrated for several physiological functions, such as the sleep/wake cycle in narcoleptic canines and OX2R-knockout mouse models [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Cellular Localization of Orexin 1 Receptor in Human Hypothalamus and Morphological Analysis of Neurons Expressing the Receptor

Vraka

Mytilinaios²,

Katsenos

et al. 2023

Biomolecules

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The orexin system is related to food behavior, energy balance, wakefulness and the reward system. It consists of the neuropeptides orexin A and B, and their receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). OX1R has selective affinity for orexin A, and is implicated in multiple functions, such as reward, emotions, and autonomic regulation. This study provides information about the OX1R distribution in human hypothalamus. The human hypothalamus, despite its small size, demonstrates a remarkable complexity in terms of cell populations and cellular morphology. Numerous studies have focused on various neurotransmitters and neuropeptides in the hypothalamus, both in animals and humans, however, there is limited experimental data on the morphological characteristics of neurons. The immunohistochemical analysis of the human hypothalamus revealed that OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The rest of the hypothalamic nuclei do not express the receptor, except for a very low number of neurons in the mammillary bodies. After identifying the nuclei and neuronal groups that were immunopositive for OX1R, a morphological and morphometric analysis of those neurons was conducted using the Golgi method. The analysis revealed that the neurons in the lateral hypothalamic area were uniform in terms of their morphological characteristics, often forming small groups of three to four neurons. A high proportion of neurons in this area (over 80%) expressed the OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results were analyzed, and shown to represent, at the cellular level, the distribution of OX1R, and we discuss the regulatory role of orexin A in the intra-hypothalamic areas, such as its special role in the plasticity of neurons, as well as in neuronal networks of the human hypothalamus.

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“…Critically, neuropeptide binding to G-protein-coupled receptors (GPCRs) in the hippocampus is able to activate numerous signalling pathways in order to modulate synaptic plasticity. For example, orexin has been shown to couple to Gq protein transducers, which results in the activation of phospholipase C. This leads to cytosolic calcium influx and the downstream activation of protein kinase C and the extracellular signal-regulated kinase (ERK) 1/2 signalling pathway [ 90 ]. Activation of this pathway has been strongly implicated in the formation and retrieval of long-term memory [ 91 ].…”

Section: Neuromodulator Function In the Central Nervous System And Dy...mentioning

confidence: 99%

Alternative Pharmacological Strategies for the Treatment of Alzheimer’s Disease: Focus on Neuromodulator Function

et al. 2022

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Alzheimer’s disease (AD) is a neurodegenerative disorder, comprising 70% of dementia diagnoses worldwide and affecting 1 in 9 people over the age of 65. However, the majority of its treatments, which predominantly target the cholinergic system, remain insufficient at reversing pathology and act simply to slow the inevitable progression of the disease. The most recent neurotransmitter-targeting drug for AD was approved in 2003, strongly suggesting that targeting neurotransmitter systems alone is unlikely to be sufficient, and that research into alternate treatment avenues is urgently required. Neuromodulators are substances released by neurons which influence neurotransmitter release and signal transmission across synapses. Neuromodulators including neuropeptides, hormones, neurotrophins, ATP and metal ions display altered function in AD, which underlies aberrant neuronal activity and pathology. However, research into how the manipulation of neuromodulators may be useful in the treatment of AD is relatively understudied. Combining neuromodulator targeting with more novel methods of drug delivery, such as the use of multi-targeted directed ligands, combinatorial drugs and encapsulated nanoparticle delivery systems, may help to overcome limitations of conventional treatments. These include difficulty crossing the blood-brain-barrier and the exertion of effects on a single target only. This review aims to highlight the ways in which neuromodulator functions are altered in AD and investigate how future therapies targeting such substances, which act upstream to classical neurotransmitter systems, may be of potential therapeutic benefit in the sustained search for more effective treatments.

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Orexin neuropeptides modulate the hippocampal-dependent memory through basolateral amygdala interconnections

Cited by 3 publications

References 34 publications

Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite

Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite

Cellular Localization of Orexin 1 Receptor in Human Hypothalamus and Morphological Analysis of Neurons Expressing the Receptor

Alternative Pharmacological Strategies for the Treatment of Alzheimer’s Disease: Focus on Neuromodulator Function

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