Chronic Sleep Restriction Outcome on the Volumetric Correlates, Neuronal and Glial Number of the Hypoglossal Nucleus in a Rat Model (Preprint)

2021 ◽  
Author(s):  
Fatemeh Karimi ◽  
Ali-Mohammad Kamali ◽  
Ali Noorafshan ◽  
Saied Karbalay-Doust ◽  
KS Rao ◽  
...  
Keyword(s):  
Brain Stem ◽  
Glial Cells ◽  
Male Rats ◽  
Sleep Restriction ◽  
Hypoglossal Nucleus ◽  
Airway Patency ◽  
Cage Control ◽  
Obstructive Sleep ◽  
The Brain ◽  
Chronic Sleep

BACKGROUND Chronic sleep restriction (CSR) is known to result in various changes in brain structures including the dorsal respiratory nuclei of the brain stem. Obstructive sleep apnea has partly been resulted from reduced tone of the muscles including the tongue which are involved in maintaining airway patency during sleep. OBJECTIVE This study aimed at investigating whether CSR may result in structural changes in the hypoglossal nerve nuclei. METHODS Three groups of male rats (each comprising 6) were randomly assigned to CSR, cage control and grid-floor control groups. CSR was imposed using the modified multi-platform box containing water for 18 hours/day for 21 days. At the end of 21 days, the rats’ brain was removed and stained through the modified Giemsa method. The hypoglossal nucleus (HGN) was evaluated through stereological approach. RESULTS The volume of HGN as well as the total number of neuronal and glial cells did not show significant differences between the cage control and the other groups (p=0.3). CONCLUSIONS The current study provided evidence to support that CSR induced by the modified multiple platform approach for 18 hours/day over 21 days in rats, neither results in volume reduction, nor neuronal and glial cells loss in the hypoglossal nuclei in the brain stem.

scholarly journals Homeostatic state of microglia in a rat model of chronic sleep restriction

SLEEP ◽  
2020 ◽  
Vol 43 (11) ◽  
Author(s):  
Shannon Hall ◽  
Samüel Deurveilher ◽  
George S Robertson ◽  
Kazue Semba
Keyword(s):  
Rat Model ◽  
Inflammatory Cytokine ◽  
Male Rats ◽  
Sleep Restriction ◽  
Mrna Levels ◽  
Prelimbic Cortex ◽  
Adaptive Responses ◽  
Brain Functions ◽  
Anti Inflammatory ◽  
Chronic Sleep

Abstract Chronic sleep restriction (CSR) negatively impacts brain functions. Whether microglia, the brain’s resident immune cells, play any role is unknown. We studied microglia responses to CSR using a rat model featuring slowly rotating wheels (3 h on/1 h off), which was previously shown to induce both homeostatic and adaptive responses in sleep and attention. Adult male rats were sleep restricted for 27 or 99 h. Control rats were housed in locked wheels. After 27 and/or 99 h of CSR, the number of cells immunoreactive for the microglia marker ionized calcium-binding adaptor molecule-1 (Iba1) and the density of Iba1 immunoreactivity were increased in 4/10 brain regions involved in sleep/wake regulation and cognition, including the prelimbic cortex, central amygdala, perifornical lateral hypothalamic area, and dorsal raphe nucleus. CSR neither induced mitosis in microglia (assessed with bromodeoxyuridine) nor impaired blood–brain barrier permeability (assessed with Evans Blue). Microglia appeared ramified in all treatment groups and, when examined quantitatively in the prelimbic cortex, their morphology was not affected by CSR. After 27 h, but not 99 h, of CSR, mRNA levels of the anti-inflammatory cytokine interleukin-10 were increased in the frontal cortex. Pro-inflammatory cytokine mRNA levels (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were unchanged. Furthermore, cortical microglia were not immunoreactive for several pro- and anti-inflammatory markers tested, but were immunoreactive for the purinergic P2Y12 receptor. These results suggest that microglia respond to CSR while remaining in a physiological state and may contribute to the previously reported homeostatic and adaptive responses to CSR.

Postnatal changes in cytochrome oxidase expressions in brain stem nuclei of rats: implications for sensitive periods

2003 ◽  
Vol 95 (6) ◽  
pp. 2285-2291 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley
Keyword(s):  
Brain Stem ◽  
Cytochrome Oxidase ◽  
Vestibular Nucleus ◽  
Glycine Receptor ◽  
Nucleus Ambiguus ◽  
Medial Vestibular Nucleus ◽  
Hypoglossal Nucleus ◽  
Motor Nucleus ◽  
Sensitive Periods ◽  
The Brain

Previously, we reported that cytochrome oxidase (CO) activity in the rat pre-Bötzinger complex (PBC) exhibited a plateau on postnatal days (P) 3–4 and a prominent decrease on P12 (Liu and Wong-Riley, J Appl Physiol 92: 923–934, 2002). These changes were correlated with a concomitant reduction in the expression of glutamate and N-methyl-d-aspartate receptor subunit 1 and an increase in GABA, GABAB, glycine receptor, and glutamate receptor 2. To determine whether changes were limited to the PBC, the present study aimed at examining the expression of CO in a number of brain stem nuclei, with or without known respiratory functions from P0 to P21 in rats: the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, nucleus raphe obscurus, dorsal motor nucleus of the vagus nerve, medial accessory olivary nucleus, spinal nucleus of the trigeminal nerve, and medial vestibular nucleus (MVe). Results indicated that, in all of the brain stem nuclei examined, CO activity exhibited a general increase with age from P0 to P21, with MVe having the slowest rise. Notably, in all of the nuclei examined except for MVe, there was a plateau or decrease at P3–P4 and a prominent rise-fall-rise pattern at P11–P13, similar to that observed in the PBC. In addition, there was a fall-rise-fall pattern at P15–P17 in these nuclei, instead of a plateau pattern in the PBC. Our data suggest that the two postnatal periods with reduced CO activity, P3–P4 and especially P12, may represent common sensitive periods for most of the brain stem nuclei with known or suspected respiratory control functions.

Transcriptional alterations of genes related to fertility decline in male rats induced by chronic sleep restriction

2020 ◽  
Vol 66 (2) ◽  
pp. 99-111 ◽  
Author(s):  
Wenyang Chen ◽  
Xingdao Guo ◽  
Zhiping Jin ◽  
Runan Li ◽  
Lixia Shen ◽  
...  
Keyword(s):  
Fertility Decline ◽  
Male Rats ◽  
Sleep Restriction ◽  
Transcriptional Alterations ◽  
Chronic Sleep

Curcumin to abrogate structural changes in the locus coeruleus following chronic sleep restriction in rats (Preprint)

2021 ◽  
Author(s):  
Ali-Mohammad Kamali ◽  
Fatemeh Karimi ◽  
Ali Noorafshan ◽  
Azam Soleimani ◽  
Saied Karbalay-Doust ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Structural Changes ◽  
Human Subjects ◽  
Grid Floor ◽  
Wire Mesh ◽  
Male Rats ◽  
Sleep Restriction ◽  
Neuroprotective Effects ◽  
Multiple Platform ◽  
Chronic Sleep

UNSTRUCTURED This study examined the consequences of chronic sleep restriction (CSR) with or without curcumin treatment on quantitative histomorphological correlates of the locus coeruleus (LC) nucleus using stereological techniques. Male rats were assigned to five groups including: 1-control (C), 2- curcumin (CUR), 3- grid floor (GF), 4- CSR and 5- CSR+ curcumin (CUR) (100 mg/kg/day). Animals in the GF group were placed on wire-mesh grids while in the CSR box (modified multiple platform paradigm). After a period of 21 days, rats were sacrificed with their brains excised and assessed using stereological procedures. Our findings revealed a 22%, 45% and 47% reduction in the total volume, the total number of neurons and glial cells of LC in CSR group as compared to the control groups, respectively (p < 0.01). Such structural changes were abrogated in the CSR+CUR compared to the CSR group. The study outcome proposed potential neuroprotective effects of CUR in our sleep-restricted rat model. Further translational approaches would shed more light on the possible clinical significance of such finding in human subjects with chronic sleep loss including those with intensive shift-work schedules.

scholarly journals Rapid Prion Neuroinvasion following Tongue Infection

2003 ◽  
Vol 77 (1) ◽  
pp. 583-591 ◽  
Author(s):  
Jason C. Bartz ◽  
Anthony E. Kincaid ◽  
Richard A. Bessen
Keyword(s):  
Brain Stem ◽  
Incubation Period ◽  
Cervical Spinal Cord ◽  
Cranial Nerves ◽  
Hypoglossal Nucleus ◽  
Vagus Nerves ◽  
Regional Lymph Nodes ◽  
Brain Invasion ◽  
Prion Infection ◽  
The Brain

ABSTRACT Food-borne transmission of prions can lead to infection of the gastrointestinal tract and neuroinvasion via the splanchnic and vagus nerves. Here we report that the transmission of transmissible mink encephalopathy (TME) is 100,000-fold more efficient by inoculation of prions into the tongues of hamsters than by oral ingestion. The incubation period following TME agent (hereinafter referred to as TME) inoculation into the lingual muscles was the shortest among the five nonneuronal routes of inoculation, including another intramuscular route. Deposition of the abnormal isoform of the prion protein, PrPSc, was first detected in the tongue and submandibular lymph node at 1 to 2 weeks following inoculation of the tongue with TME. PrPSc deposits in the tongue were associated with individual axons, and the initial appearance of TME in the brain stem was found in the hypoglossal nucleus at 2 weeks postinfection. At later time points, PrPSc was localized to brain cell groups that directly project to the hypoglossal nucleus, indicating the transneuronal spread of TME. TME PrPSc entry into the brain stem preceded PrPSc detection in the rostral cervical spinal cord. These results demonstrate that TME can replicate in both the tongue and regional lymph nodes but indicate that the faster route of brain invasion is via retrograde axonal transport within the hypoglossal nerve to the hypoglossal nucleus. Topical application of TME to a superficial wound on the surface of the tongue resulted in a higher incidence of disease and a shorter incubation period than with oral TME ingestion. Therefore, abrasions of the tongue in livestock and humans may predispose a host to oral prion infection of the tongue-associated cranial nerves. In a related study, PrPSc was detected in tongues following the intracerebral inoculation of six hamster-adapted prion strains, which demonstrates that prions can also travel from the brain to the tongue in the anterograde direction along the tongue-associated cranial nerves. These findings suggest that food products containing ruminant or cervid tongue may be a potential source of prion infection for humans.

scholarly journals The development of the weanling rat during nutritionally - induced growth retardation and during early rehabilitation

1974 ◽  
Vol 32 (2) ◽  
pp. 301-312 ◽  
Author(s):  
P. A. McAnulty ◽  
J. W. T. Dickerson
Keyword(s):  
Body Weight ◽  
Brain Stem ◽  
Relative Weight ◽  
Cellular Level ◽  
Normal Diet ◽  
The Body ◽  
Male Rats ◽  
Gut Contents ◽  
The Brain ◽  
Unrestricted Diet

1. Weanling (24-d-old) male rats were maintained at their body-weight for 1 month by restricting the intake of their normal diet. The animals were then rehabilitated for 0, 3, 7, 10 or 16 d. Control animals were given an unrestricted diet and some killed at the same body-weight as the experimental animals and others at the same age.2. The forebrain, cerebellum, brain stem, heart, lungs, liver, spleen, kidneys, testes, and three sections of the alimentary tract were weighed, and DNA, RNA and protein contents were determined in the brain parts and liver.3. During rehabilitation the weight of the body, corrected for the weight of the gut contents, showed a rapid gain between 7 and 10 d, which was synchronous with a rapid gain in weight of the testes.4. The weight of the majority of organs relative to body-weight was maintained during both undernutrition and rehabilitation, the most marked exceptions being the stomach, which increased in relative weight during undernutrition, and maintained a high relative weight during rehabilitation, and the spleen, which lost weight during undernutrition, and on rehabilitation gained weight very rapidly to achieve a high relative weight.5. The weight of the forebrain fell during undernutrition, due to a loss of water, and the weight of the brain stem rose. In the forebrain, DNA and the protein: DNA ratio were unchanged throughout, whereas a marked loss of RNA occurred during undernutrition, which was restored during rehabilitation.6. The weight of the liver remained unchanged during undernutrition, despite increases in the amounts of DNA and protein. The amount of liver RNA decreased during undernutrition, but on rehabilitation showed an immediate and rapid increase. The variables measured in the liver were normal relative to body-weight, within 10 d of rehabilitation.7. It is suggested that the growth occurring on rehabilitation is a balanced response to a single stimulus, partly mediated at the cellular level by RNA.

Chronic intermittent hypoxia alters neurotransmission from lateral paragigantocellular nucleus to parasympathetic cardiac neurons in the brain stem

2015 ◽  
Vol 113 (1) ◽  
pp. 380-389 ◽  
Author(s):  
Olga Dergacheva
Keyword(s):  
Brain Stem ◽  
Rem Sleep ◽  
Cardiovascular Events ◽  
Intermittent Hypoxia ◽  
Female Rats ◽  
Parasympathetic Activity ◽  
Male Rats ◽  
Chronic Intermittent Hypoxia ◽  
Gabaergic Neurotransmission ◽  
The Brain

Patients with sleep-related disorders, including obstructive sleep apnea (OSA), have an increased risk of cardiovascular diseases. OSA events are more severe in rapid eye movement (REM) sleep. REM sleep further increases the risk of adverse cardiovascular events by diminishing cardioprotective parasympathetic activity. The mechanisms underlying REM sleep-related reduction in parasympathetic activity likely include activation of inhibitory input to cardiac vagal neurons (CVNs) in the brain stem originating from the lateral paragigantocellular nucleus (LPGi), a nucleus that plays a role in REM sleep control. This study tests the hypothesis that chronic intermittent hypoxia and hypercapnia (CIHH), an animal model of OSA, inhibits CVNs because of exaggeration of the GABAergic pathway from the LPGi to CVNs. GABAergic neurotransmission to CVNs evoked by electrical stimulation of the LPGi was examined with whole cell patch-clamp recordings in an in vitro brain slice preparation in rats exposed to CIHH and control rats. GABAergic synaptic events were enhanced after 4-wk CIHH in both male and female rats, to a greater degree in males. Acute hypoxia and hypercapnia (H/H) reversibly diminished the LPGi-evoked GABAergic neurotransmission to CVNs. However, GABAergic synaptic events were enhanced after acute H/H in CIHH male animals. Orexin-A elicited a reversible inhibition of LPGi-evoked GABAergic currents in control animals but evoked no significant changes in CIHH male rats. In conclusion, exaggerated inhibitory neurotransmission from the LPGi to CVNs in CIHH animals would reduce cardioprotective parasympathetic activity and enhance the risk of adverse cardiovascular events.

scholarly journals Metabolic Disturbances Induced by Sleep Restriction as Potential Triggers for Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Jesús Enrique García-Aviles ◽  
Rebeca Méndez-Hernández ◽  
Mara A. Guzmán-Ruiz ◽  
Miguel Cruz ◽  
Natalí N. Guerrero-Vargas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficit ◽  
Amyloid Β ◽  
Sleep Restriction ◽  
Amyloid Β Peptide ◽  
Metabolic Disturbances ◽  
The Brain ◽  
Chronic Sleep

Sleep has a major role in learning, memory consolidation, and metabolic function. Although it is known that sleep restriction increases the accumulation of amyloid β peptide (Aβ) and the risk to develop Alzheimer’s disease (AD), the mechanism behind these effects remains unknown. In this review, we discuss how chronic sleep restriction induces metabolic and cognitive impairments that could result in the development of AD in late life. Here, we integrate evidence regarding mechanisms whereby metabolic signaling becomes disturbed after short or chronic sleep restriction in the context of cognitive impairment, particularly in the accumulation of Aβ in the brain. We also discuss the role of the blood-brain barrier in sleep restriction with an emphasis on the transport of metabolic signals into the brain and Aβ clearance. This review presents the unexplored possibility that the alteration of peripheral metabolic signals induced by sleep restriction, especially insulin resistance, is responsible for cognitive deficit and, subsequently, implicated in AD development.

scholarly journals Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation

2015 ◽  
Vol 114 (2) ◽  
pp. 893-901 ◽  
Author(s):  
Linda C. Lundblad ◽  
Rania H. Fatouleh ◽  
David K. McKenzie ◽  
Vaughan G. Macefield ◽  
Luke A. Henderson
Keyword(s):  
Brain Stem ◽  
Signal Intensity ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Bold Signal ◽  
Functional Changes ◽  
Cpap Treatment ◽  
Obstructive Sleep ◽  
Medullary Raphe ◽  
The Brain

Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity.

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