Jerome Siegel - Academia.edu (original) (raw)

Papers by Jerome Siegel

Research paper thumbnail of Striking cessation of cataplexy by opioids

Journal of Sleep Research, Oct 12, 2018

Research paper thumbnail of Attenuated Circadian Rhythms in Mice Lacking the<i>Prokineticin 2</i>Gene

The Journal of Neuroscience, Nov 8, 2006

Research paper thumbnail of Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

The Journal of Neuroscience, Dec 26, 2007

Research paper thumbnail of Orexin receptors in GtoPdb v.2023.1

IUPHAR/BPS guide to pharmacology CITE, Apr 26, 2023

Research paper thumbnail of Substantia nigra pars reticulata-mediated sleep and motor activity regulation

Research paper thumbnail of Fur Seals Display a Strong Drive for Bilateral Slow-Wave Sleep While on Land

The Journal of Neuroscience, Nov 26, 2008

Research paper thumbnail of Activation of Pontine and Medullary Motor Inhibitory Regions Reduces Discharge in Neurons Located in the Locus Coeruleus and the Anatomical Equivalent of the Midbrain Locomotor Region

The Journal of Neuroscience, Nov 15, 2000

Research paper thumbnail of Fur Seals Suppress REM Sleep for Very Long Periods without Subsequent Rebound

Current Biology, Jun 1, 2018

Research paper thumbnail of A Consensus Definition of Cataplexy in Mouse Models of Narcolepsy

Research paper thumbnail of New pathways and data on rapid eye movement sleep behaviour disorder in a rat model

Sleep Medicine, Aug 1, 2013

Research paper thumbnail of Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: An<i>In Vivo</i>Microdialysis Study

The Journal of Neuroscience, Feb 15, 2003

Research paper thumbnail of 0012 REM Sleep in Ostrich Chicks

Sleep, 2020

Introduction It was reported that adult ostriches displayed the longest REM sleep episodes (up to... more Introduction It was reported that adult ostriches displayed the longest REM sleep episodes (up to 5 min) and more REM sleep (24% of the nighttime) than any other avian species. In all mammals studied so far REM sleep predominates at early age suggesting it promotes development of the brain. The aim of this study was to examine REM sleep in ostrich chicks. Methods EEG, electrooculogram and electromyogram of the neck muscles were recorded in 4 chronically implanted 2–3 month old ostrich chicks over 3 nights. The last night was scored in 4-sec epochs for waking, nonREM and REM sleep. Results NonREM sleep and REM sleep in the ostrich chicks occurred when they were sitting or lying with the head held above the ground or rested on the ground. REM sleep was characterized by distinct rapid eye movements, head drops and eye closure. The amplitude of the EEG during episodes of REM sleep ranged between low voltage EEG, as recorded during quiet waking and high voltage slow waves, as recorded du...

Research paper thumbnail of The Neural Control of Sleep and Waking

Research paper thumbnail of Locus coeruleus neurons: cessation of activity during cataplexy

Research paper thumbnail of Neuronal Degeneration in Canine Narcolepsy

The Journal of Neuroscience, 1999

Research paper thumbnail of Effects of sodium oxybate on hypocretin/orexin and locus coeruleus neurons

Sleep, May 8, 2023

Longterm use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate (GHB)) attenuates the ca... more Longterm use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate (GHB)) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and longterm opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.

Research paper thumbnail of Hypocretin (orexin) and melanin concentrating hormone loss and the symptoms of Parkinson's disease

Research paper thumbnail of Consensus guidelines on the construct validity of rodent models of restless legs syndrome

Disease Models & Mechanisms

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete.... more Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most ap...

Research paper thumbnail of Hypocretin/Orexin Interactions with Norepinephrine Contribute to the Opiate Withdrawal Syndrome

The Journal of Neuroscience, 2021

We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a ... more We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt)-producing neurons. However, it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including norepinephrine containing structures locus coeruleus (LC) and A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques, we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine-containing neuronal cell number. We show that the increase in TH is completely dependent on Hcrt innervation. The A1/A2 regions were unaffected by morphine treatment. Manipulation of the Hcrt system may affect opioid addiction and withdrawal.SIGNIFICANCE STATEMENTPreviously, we have sh...

Research paper thumbnail of 0284 Sleep-active Neurons In The Median Preoptic Nucleus Exhibit Signs Of Physiological Dysfunction In Aging

Sleep, 2018

found in young individuals exposed to a dawn simulation light, an increase in both heart rate and... more found in young individuals exposed to a dawn simulation light, an increase in both heart rate and sympathovagal tone prior to awakening and a decrease in sleepiness. In this study we will determine whether a dawn simulation light is able to decrease sleepiness in older adults and increase their cardiovascular tone such that they would have reduced or absent postural hypotension when they get out of bed in the morning. Methods: In this preliminary study, seven older patients (69.71 ± 10.26 y) who experienced morning dizziness underwent two overnight stays in the laboratory. During both nights, they slept in complete darkness, except for the last 30 minutes of one night, where a dawn simulation light was on. Sleepiness and balance were tested before and after the night of sleep; heart rate, EEG and blood pressure were continuously recorded. Results: We found no significant effects of "light" or "time" on sleepiness upon awakening, nor were there changes in measures of standing or ambulatory balance or heart rate. Blood pressure data are still under analysis. Conclusion: Unlike younger adults, we found no significant effect on sleepiness or heart rate after a dawn simulation light exposure in older adults. We also did not see an impact on measures of balance. Further analyses and an increased number of participants are planned. Support (If Any): none.

Research paper thumbnail of Striking cessation of cataplexy by opioids

Journal of Sleep Research, Oct 12, 2018

Research paper thumbnail of Attenuated Circadian Rhythms in Mice Lacking the<i>Prokineticin 2</i>Gene

The Journal of Neuroscience, Nov 8, 2006

Research paper thumbnail of Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

The Journal of Neuroscience, Dec 26, 2007

Research paper thumbnail of Orexin receptors in GtoPdb v.2023.1

IUPHAR/BPS guide to pharmacology CITE, Apr 26, 2023

Research paper thumbnail of Substantia nigra pars reticulata-mediated sleep and motor activity regulation

Research paper thumbnail of Fur Seals Display a Strong Drive for Bilateral Slow-Wave Sleep While on Land

The Journal of Neuroscience, Nov 26, 2008

Research paper thumbnail of Activation of Pontine and Medullary Motor Inhibitory Regions Reduces Discharge in Neurons Located in the Locus Coeruleus and the Anatomical Equivalent of the Midbrain Locomotor Region

The Journal of Neuroscience, Nov 15, 2000

Research paper thumbnail of Fur Seals Suppress REM Sleep for Very Long Periods without Subsequent Rebound

Current Biology, Jun 1, 2018

Research paper thumbnail of A Consensus Definition of Cataplexy in Mouse Models of Narcolepsy

Research paper thumbnail of New pathways and data on rapid eye movement sleep behaviour disorder in a rat model

Sleep Medicine, Aug 1, 2013

Research paper thumbnail of Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: An<i>In Vivo</i>Microdialysis Study

The Journal of Neuroscience, Feb 15, 2003

Research paper thumbnail of 0012 REM Sleep in Ostrich Chicks

Sleep, 2020

Introduction It was reported that adult ostriches displayed the longest REM sleep episodes (up to... more Introduction It was reported that adult ostriches displayed the longest REM sleep episodes (up to 5 min) and more REM sleep (24% of the nighttime) than any other avian species. In all mammals studied so far REM sleep predominates at early age suggesting it promotes development of the brain. The aim of this study was to examine REM sleep in ostrich chicks. Methods EEG, electrooculogram and electromyogram of the neck muscles were recorded in 4 chronically implanted 2–3 month old ostrich chicks over 3 nights. The last night was scored in 4-sec epochs for waking, nonREM and REM sleep. Results NonREM sleep and REM sleep in the ostrich chicks occurred when they were sitting or lying with the head held above the ground or rested on the ground. REM sleep was characterized by distinct rapid eye movements, head drops and eye closure. The amplitude of the EEG during episodes of REM sleep ranged between low voltage EEG, as recorded during quiet waking and high voltage slow waves, as recorded du...

Research paper thumbnail of The Neural Control of Sleep and Waking

Research paper thumbnail of Locus coeruleus neurons: cessation of activity during cataplexy

Research paper thumbnail of Neuronal Degeneration in Canine Narcolepsy

The Journal of Neuroscience, 1999

Research paper thumbnail of Effects of sodium oxybate on hypocretin/orexin and locus coeruleus neurons

Sleep, May 8, 2023

Longterm use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate (GHB)) attenuates the ca... more Longterm use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate (GHB)) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and longterm opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.

Research paper thumbnail of Hypocretin (orexin) and melanin concentrating hormone loss and the symptoms of Parkinson's disease

Research paper thumbnail of Consensus guidelines on the construct validity of rodent models of restless legs syndrome

Disease Models & Mechanisms

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete.... more Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most ap...

Research paper thumbnail of Hypocretin/Orexin Interactions with Norepinephrine Contribute to the Opiate Withdrawal Syndrome

The Journal of Neuroscience, 2021

We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a ... more We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt)-producing neurons. However, it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including norepinephrine containing structures locus coeruleus (LC) and A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques, we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine-containing neuronal cell number. We show that the increase in TH is completely dependent on Hcrt innervation. The A1/A2 regions were unaffected by morphine treatment. Manipulation of the Hcrt system may affect opioid addiction and withdrawal.SIGNIFICANCE STATEMENTPreviously, we have sh...

Research paper thumbnail of 0284 Sleep-active Neurons In The Median Preoptic Nucleus Exhibit Signs Of Physiological Dysfunction In Aging

Sleep, 2018

found in young individuals exposed to a dawn simulation light, an increase in both heart rate and... more found in young individuals exposed to a dawn simulation light, an increase in both heart rate and sympathovagal tone prior to awakening and a decrease in sleepiness. In this study we will determine whether a dawn simulation light is able to decrease sleepiness in older adults and increase their cardiovascular tone such that they would have reduced or absent postural hypotension when they get out of bed in the morning. Methods: In this preliminary study, seven older patients (69.71 ± 10.26 y) who experienced morning dizziness underwent two overnight stays in the laboratory. During both nights, they slept in complete darkness, except for the last 30 minutes of one night, where a dawn simulation light was on. Sleepiness and balance were tested before and after the night of sleep; heart rate, EEG and blood pressure were continuously recorded. Results: We found no significant effects of "light" or "time" on sleepiness upon awakening, nor were there changes in measures of standing or ambulatory balance or heart rate. Blood pressure data are still under analysis. Conclusion: Unlike younger adults, we found no significant effect on sleepiness or heart rate after a dawn simulation light exposure in older adults. We also did not see an impact on measures of balance. Further analyses and an increased number of participants are planned. Support (If Any): none.