scholarly journals Acute and Chronic Sleep Deprivation-Related Changes in N-methyl-D-aspartate Receptor—Nitric Oxide Signalling in the Rat Cerebral Cortex with Reference to Aging and Brain Lateralization

2019 ◽  
Vol 20 (13) ◽  
pp. 3273 ◽  
Author(s):  
Zdenka Kristofikova ◽  
Jana Sirova ◽  
Jan Klaschka ◽  
Saak V. Ovsepian

Aging and chronic sleep deprivation (SD) are well-recognized risk factors for Alzheimer’s disease (AD), with N-methyl-D-aspartate receptor (NMDA) and downstream nitric oxide (NO) signalling implicated in the process. Herein, we investigate the impact of the age- and acute or chronic SD-dependent changes on the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) and on the activities of NO synthase (NOS) isoforms in the cortex of Wistar rats, with reference to cerebral lateralization. In young adult controls, somewhat lateralized seasonal variations in neuronal and endothelial NOS have been observed. In aged rats, overall decreases in NR1, NR2A, and NR2B expression and reduction in neuronal and endothelial NOS activities were found. The age-dependent changes in NR1 and NR2B significantly correlated with neuronal NOS in both hemispheres. Changes evoked by chronic SD (dysfunction of endothelial NOS and the increasing role of NR2A) differed from those evoked by acute SD (increase in inducible NOS in the right side). Collectively, these results demonstrate age-dependent regulation of the level of NMDA receptor subunits and downstream NOS isoforms throughout the rat brain, which could be partly mimicked by SD. As described herein, age and SD alterations in the prevalence of NMDA receptors and NOS could contribute towards cognitive decline in the elderly, as well as in the pathobiology of AD and the neurodegenerative process.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tiziana Imbriglio ◽  
Remy Verhaeghe ◽  
Nico Antenucci ◽  
Stefania Maccari ◽  
Giuseppe Battaglia ◽  
...  

AbstractmGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5−/− mice and wild-type littermates at three developmental time points (PND9, − 21, and − 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5−/− mice at PND21. In contrast, at PND9, expression of the GluN2B subunit was enhanced, whereas expression of GluN2A and GluN2D subunits was reduced in both regions. These modifications were transient and disappeared in the adult life (PND75). Changes in the transcripts of interneuron-related genes (encoding parvalbumin, somatostatin, vasoactive intestinal peptide, reelin, and the two isoforms of glutamate decarboxylase) were also observed in mGlu5−/− mice across postnatal development. For example, the transcript encoding parvalbumin was up-regulated in the prefrontal cortex of mGlu5−/− mice at PND9 and PND21, whereas it was significantly reduced at PND75. These findings suggest that in mGlu5−/− mice a transient overexpression of NMDA receptor subunits may compensate for the lack of the NMDA receptor partner, mGlu5. Interestingly, in mGlu5−/− mice the behavioral response to the NMDA channel blocker, MK-801, was significantly increased at PND21, and largely reduced at PND75. The impact of adaptive changes in the expression of NMDA receptor subunits should be taken into account when mGlu5−/− mice are used for developmental studies.


2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 246-252
Author(s):  
Devon A Hansen ◽  
Brieann C Satterfield ◽  
Matthew E Layton ◽  
Hans P A Van Dongen

ABSTRACT Introduction Military operations often involve intense exposure to stressors combined with acute sleep deprivation, while military personnel also experience high prevalence of chronic sleep deficiency from insomnia and other sleep disorders. However, the impact of acute and chronic sleep deficiency on physiologic stressor responses is poorly understood. In a controlled laboratory study with normal sleepers and individuals with chronic sleep-onset insomnia, we measured responses to an acute stressor administered in a sleep deprivation condition or a control condition. Methods Twenty-two adults (aged 22-40 years; 16 females)—11 healthy normal sleepers and 11 individuals with sleep-onset insomnia—completed a 5-day (4-night) in-laboratory study. After an adaptation day and a baseline day, subjects were assigned to a 38-hour total sleep deprivation (TSD) condition or a control condition; the study ended with a recovery day. At 8:00 PM after 36 hours awake in the sleep deprivation condition or 12 hours awake in the control condition, subjects underwent a Maastricht Acute Stress Test (MAST). Salivary cortisol was measured immediately before the MAST at 8:00 PM, every 15 minutes after the MAST from 8:15 PM until 9:15 PM, and 30 minutes later at 9:45 PM. Baseline salivary cortisol was collected in the evening of the baseline day. Additionally, before and immediately upon completion of the MAST, self-report ratings of affect and pain were collected. Results The MAST elicited a stressor response in both normal sleepers and individuals with sleep-onset insomnia, regardless of the condition, as evidenced by increases in negative affect and pain ratings. Relative to baseline, cortisol levels increased immediately following the MAST, peaked 30 minutes later, and then gradually returned to pre-MAST levels. At the cortisol peak, there was a significant difference across groups and conditions, reflecting a pronounced blunting of the cortisol response in the normal sleepers in the TSD condition and the sleep-onset insomnia group in both the TSD and control conditions. Conclusions Blunted stressor reactivity as a result of sleep deficiency, whether acute or chronic, may reflect reduced resiliency attributable to allostatic load and may put warfighters at increased risk in high-stakes, rapid response scenarios.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A323-A323
Author(s):  
Neeley Remmers ◽  
Michael Anderson ◽  
John Nelson

Abstract Introduction Each year, 3 million older people are treated in emergency departments for fall-related injuries. These falls can lead to serious injuries and expensive health care costs. Some have looked into the relationship between chronic sleep disturbances and falls linking chronic sleep deprivation or excessive sleep to falling. Here, we present a unique case of chronic sleep deprivation causing sleep attacks or micro-sleeps with atonia causing falls. Report of case(s) We present a 75-year-old F with a history of increased daily falls up to 4x per day that began 3 years ago. She denies any triggering events, auras, frequent tripping, loss of balance or weakness. Reportedly, she will be walking along then suddenly falls. She is aware that she is falling yet feels as though she cannot prevent/stop the fall or break her fall. No one has witnessed her fall, but is frequently found lying on the floor. She has never sustained a serious injury as a result of her falls. She has an 8 year history of restless legs syndrome treated with ropinirole and a 10 year history of obstructive sleep apnea (OSA) treated with CPAP. Her general bedtime is 2200 and wake-time is 0400 with an average 3–4 hrs of quality sleep per night for many years. She endorses severe daytime hypersomnolence and chronic hypoxemia on 3L home oxygen. We hypothesized her falls were secondary to sleep attacks or micro-sleeps where she enters REM sleep and develops atonia. Nocturnal sleep study followed by MSLT showed severe OSA with severe, persistent daytime sleeping with REM sleep and atonia. She had a mean sleep latency of 2 minutes with 1 sleep-onset REM period. We started NIPPV with supplemental oxygen treatment, and within 4 months her daytime hypersomnolence resolved, exercise intolerance improved, saturations improved to 89–90% on room air, and has <1 fall per day. Conclusion Here, we presented a unique case of a 75 yo F with recurrent falls secondary to chronic sleep deprivation causing micro-sleeps involving REM sleep and atonia. She was treated with NIPPV which improved her oxygenation and reduced her number of falls to <1 per day. Support (if any):


Life Sciences ◽  
2020 ◽  
Vol 263 ◽  
pp. 118524
Author(s):  
Hanqing Tang ◽  
Keming Li ◽  
Xibin Dou ◽  
Yufeng Zhao ◽  
Chunchuan Huang ◽  
...  

2020 ◽  
Vol 24 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Caterina Lombardo ◽  
Andrea Ballesio ◽  
Giordana Gasparrini ◽  
Silvia Cerolini

SLEEP ◽  
2013 ◽  
Vol 36 (4) ◽  
pp. 601-607 ◽  
Author(s):  
Christopher G. Vecsey ◽  
Mathieu E. J. Wimmer ◽  
Robbert Havekes ◽  
Alan J. Park ◽  
Isaac J. Perron ◽  
...  

2020 ◽  
Vol 14 ◽  
Author(s):  
Luis A. De Jesús-Olmo ◽  
Norma Rodríguez ◽  
Marcelo Francia ◽  
Jonathan Alemán-Rios ◽  
Carlos J. Pacheco-Agosto ◽  
...  

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