Journal article
Deep brain stimulation of hypothalamus for narcolepsy-cataplexy in mice
Brain stimulation, v 13(5), pp 1305-1316
01 Sep 2020
PMID: 32320748
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Narcolepsy type 1 (NT1, narcolepsy with cataplexy) is a disabling neurological disorder caused by loss of excitatory orexin neurons from the hypothalamus and is characterized by decreased motivation, sleep-wake fragmentation, intrusion of rapid-eye-movement sleep (REMS) during wake, and abrupt loss of muscle tone, called cataplexy, in response to sudden emotions.
Objective: We investigated whether subcortical stimulation, analogous to clinical deep brain stimulation (DBS), would ameliorate NT1 using a validated transgenic mouse model with postnatal orexin neuron degeneration.
Methods: Using implanted electrodes in freely behaving mice, the immediate and prolonged effects of DBS were determined upon behavior using continuous video-electroencephalogram-electromyogram (video/EEG/EMG) and locomotor activity, and neural activation in brain sections, using immunohistochemical labeling of the immediate early gene product c-Fos.
Results: Brief 10-s stimulation to the region of the lateral hypothalamus and zona incerta (LH/ZI) doseresponsively reversed established sleep and cataplexy episodes without negative sequelae. Continuous 3-h stimulation increased ambulation, improved sleep-wake consolidation, and ameliorated cataplexy. Brain c-Fos from mice sacrificed after 90 min of DBS revealed dose-responsive neural activation within wake-active nuclei of the basal forebrain, hypothalamus, thalamus, and ventral midbrain.
Conclusion: Acute and continuous LH/ZI DBS enhanced behavioral state control in a mouse model of NT1, supporting the feasibility of clinical DBS for NT1 and other sleep-wake disorders. (C) 2020 Published by Elsevier Inc.
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Details
- Title
- Deep brain stimulation of hypothalamus for narcolepsy-cataplexy in mice
- Creators
- Anna A. Rogers - Emory UniversityLauren M. Aiani - Emory UniversityLou T. Blanpain - Emory UniversitySun Yuxian - Emory UniversityRenee Moore - Emory UniversityJon T. Willie - Emory University
- Publication Details
- Brain stimulation, v 13(5), pp 1305-1316
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- Emory University Research Committee Award of the Georgia Clinical & Translational Science Alliance Neurosurgery Research and Education Foundation Young Clinician Investigator Award of the Georgia Clinical & Translational Science Alliance Pilot Translational and Clinical Studies Program Award of the Georgia Clinical & Translational Science Alliance Sleep Research Society Foundation Career Development Award of the Georgia Clinical & Translational Science Alliance
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000573961300026
- Scopus ID
- 2-s2.0-85087031049
- Other Identifier
- 991021448031704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Neurosciences