Eszopiclone Prevents Excitotoxicity and Neurodegeneration in the Hippocampus Induced by Experimental Apnea

Fung, Simon J.; Xi, Ming-Chu; Zhang, Jian Hua; Yamuy, Jack; Sampogna, Sharon; Tsai, Kevin; Lim, V. G.; Morales, Francisco R.; Chase, Michael H.

doi:10.1093/sleep/32.12.1593

Cited by 8 publications

(5 citation statements)

References 53 publications

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“…This hypothesis is supported by the pivotal role played by the amygdala in emotional and cerebral circuits (LeDoux,2000) and related to pathological conditions, such as depression, wherein amygdaloid dysfunction together with disturbances of AS has been shown to occur (Maquet and Franck,1997). Recently, we demonstrated that recurrent apnea in guinea pigs (which models obstructive sleep apnea syndrome in humans; Fung et al,2007,2009) produces neurodegeneration/apoptosis in CNA neurons (Zhang et al,2009). This finding suggests that dysfunction of the excitatory CNA pathway to the NPO may contribute to AS disturbances as well as to the generation of comorbidities that occur due to pathologies that involve the amygdala and others that also occur in conjunction with obstructive sleep apnea.…”

Section: Discussionmentioning

confidence: 99%

Projection neurons from the central nucleus of the amygdala to the nucleus pontis oralis

Fung

Zhang

et al. 2010

J. Neurosci. Res.

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The present retrograde labeling study was designed to determine the presence and pattern of projections from individual subdivisions of the central nucleus of the amygdala (CNA) to the nucleus pontis oralis (NPO), which is a critical brainstem site involved for the generation and maintenance of active (REM) sleep. Projections from the CNA were labeled with the retrograde tracer, cholera toxin B-subunit (CTB), which was injected, unilaterally, via microiontophoresis, into the NPO. Sections of the amygdala were immunostained in order to identify CTB-labeled CNA neurons and CNA neurons that contained CTB plus the vesicular glutamate transporter 2 (VGLUT2), which is a marker for glutamatergic neurons. Histological analyses revealed that retrogradely-labeled neurons that project to the NPO were localized, ipsilaterally, within the medial, lateral and capsular subdivisions of the CNA. In addition, a substantial proportion (24%) of all retrogradely-labeled CNA neurons also exhibited VGLUT2 immunoreactivity. The present study demonstrates that glutamatergic neurons, which are present within various subdivisions of the CNA, project directly to the NPO. These data lend credence to the hypothesis that NPO neurons that are involved in the control of active sleep are activated by glutamatergic projections from the amygdala.

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Section: Discussionmentioning

confidence: 99%

Projection neurons from the central nucleus of the amygdala to the nucleus pontis oralis

Fung

Zhang

et al. 2010

J. Neurosci. Res.

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“…Drugs enhancing GABA-A signaling may thus represent potential strategies to treat or prevent the progressive motorneuron degeneration in ALS patients (Supplementary Table 7). In this regard, some GABA-A agonists (ganaxolone, clomethiazole, GT 1061, clorazepate, zolpidem, eszopiclone, pentobarbital, GT 1061) have shown to prevent excitotoxicity and neuronal loss, exerting neuroprotective effects in several neurological disorders, such as Alzheimer's and Parkinson's [88][89][90][91].…”

Section: Review Morello and Cavallaromentioning

confidence: 99%

Transcriptional Analysis Reveals Distinct Subtypes in Amyotrophic Lateral Sclerosis: Implications for Personalized Therapy

Morello

Cavallaro

2015

Future Med. Chem.

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Amyotrophic lateral sclerosis (ALS) is an incurable disease, caused by the loss of the upper and lower motor neurons. The lack of therapeutic progress is mainly due to the insufficient understanding of complexity and heterogeneity underlying the pathogenic mechanisms of ALS. Recently, we analyzed whole-genome expression profiles of motor cortex of sporadic ALS patients, classifying them into two subgroups characterized by differentially expressed genes and pathways. Some of the deregulated genes encode proteins, which are primary targets of drugs currently in preclinical or clinical studies for several clinical conditions, including neurodegenerative diseases. In this review, we discuss in-depth the potential role of these candidate targets in ALS pathogenesis, highlighting their possible relevance for personalized ALS treatments.

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“…This finding is especially significant because almost every known neuroprotective substance acts by suppressing or inhibiting neural activity. Consequently, even though hypocretin is an excitatory neuropeptide, in this case its effects are more closely related to those produced by inhibitory neurotransmitters (54,189).…”

Section: Control Of Survival-related Processes By the Hypocretinergicmentioning

confidence: 99%

A unified survival theory of the functioning of the hypocretinergic system

Chase

2013

Journal of Applied Physiology

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This article advances the theory that the hypocretinergic (orexinergic) system initiates, coordinates, and maintains survival behaviors and survival-related processes (i.e., the Unified Survival Theory of the Functioning of the Hypocretinergic System or "Unified Hypocretinergic Survival Theory"). A priori presumptive support for the Unified Hypocretinergic Survival Theory emanates from the fact that neurons that contain hypocretin are located in the key executive central nervous system (CNS) site, the lateral hypothalamus, that for decades has been well-documented to govern core survival behaviors such as fight, flight, and food consumption. In addition, the hypocretinergic system exhibits the requisite morphological and electrophysiological capabilities to control survival behaviors and related processes. Complementary behavioral data demonstrate that all facets of "survival" are coordinated by the hypocretinergic system and that hypocretinergic directives are not promulgated except during survival behaviors. Importantly, it has been shown that survival behaviors are selectively impacted when the hypocretinergic system is impaired or rendered nonfunctional, whereas other behaviors are relatively unaffected. The Unified Hypocretinergic Survival Theory resolves the disparate, perplexing, and often paradoxical-appearing results of previous studies; it also provides a foundation for future hypothesis-driven basic science and clinical explorations of the hypocretinergic system.

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Eszopiclone Prevents Excitotoxicity and Neurodegeneration in the Hippocampus Induced by Experimental Apnea

Cited by 8 publications

References 53 publications

Projection neurons from the central nucleus of the amygdala to the nucleus pontis oralis

Projection neurons from the central nucleus of the amygdala to the nucleus pontis oralis

Transcriptional Analysis Reveals Distinct Subtypes in Amyotrophic Lateral Sclerosis: Implications for Personalized Therapy

A unified survival theory of the functioning of the hypocretinergic system

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