Sleep deprivation

===The brain===

==== Temporary ====
One study suggested, based on neuroimaging, that 35 hours of total sleep deprivation in healthy controls negatively affected the brain's ability to put an emotional event into the proper perspective and make a controlled, suitable response to the event.<ref>{{cite journal | vauthors = Yoo SS, Gujar N, Hu P, Jolesz FA, Walker MP | title = The human emotional brain without sleep--a prefrontal amygdala disconnect | journal = Current Biology | volume = 17 | issue = 20 | pages = R877–R878 | date = October 2007 | pmid = 17956744 | doi = 10.1016/j.cub.2007.08.007 | s2cid = 9008816 | doi-access = free | bibcode = 2007CBio...17.R877Y }}</ref>

According to the latest research, lack of sleep may cause more harm than previously thought and may lead to the permanent loss of brain cells.<ref>{{Cite web |date=2014-03-21 |title=最新研究：睡眠不足会永久损伤脑细胞 | trans-title = Latest research: Lack of sleep can permanently damage brain cells |url=https://www.bbc.com/zhongwen/simp/science/2014/03/140321_lost_sleep |access-date=2023-12-05 |website=BBC News 中文 (Chinese) |language=zh-hans}}</ref> The negative effects of sleep deprivation on alertness and cognitive performance suggest decreases in brain activity and function. These changes primarily occur in two regions: the [[thalamus]], a structure involved in alertness and attention, and the [[prefrontal cortex]], a region subserving alertness, attention, and higher-order cognitive processes.<ref name="performance" /> This was the finding of an American study in 2000. Seventeen men in their 20s were tested. Sleep deprivation was progressive, with measurements of glucose (absolute regional CMRglu), cognitive performance, alertness, mood, and subjective experiences collected after 0, 24, 48, and 72 hours of sleep deprivation. Additional measures of alertness, cognitive performance, and mood were collected at fixed intervals. [[Positron emission tomography|PET]] scans were used, and attention was paid to the circadian rhythm of cognitive performance.<ref name="performance" /> Interestingly, the effects of sleep deprivation appear to be constant across "night owls" and "early birds", or different sleep chronotypes, as revealed by [[fMRI]] and [[graph theory]].<ref>{{cite journal | vauthors = Farahani FV, Fafrowicz M, Karwowski W, Douglas PK, Domagalik A, Beldzik E, Oginska H, Marek T | title = Effects of Chronic Sleep Restriction on the Brain Functional Network, as Revealed by Graph Theory | journal = Frontiers in Neuroscience | volume = 13 | pages = 1087 | date = 11 October 2019 | pmid = 31680823 | pmc = 6807652 | doi = 10.3389/fnins.2019.01087 | publisher = Frontiers Media SA | doi-access = free }}</ref>

==== Lasting ====
[[File:Effect of REM sleep deprivation on the mitochondrial structure of neurons in rats.jpg|thumb|REM sleep deprivation causes swollen mitochondria in neurons (caused by [[cytochrome c]]); noradrenaline receptor blockers keep their inner cristae intact.]]
Studies on rodents show that the response to neuronal injury due to acute sleep deprivation is adaptative before three hours of sleep loss per night and becomes maladaptative, and [[apoptosis]] occurs after.<ref>{{cite journal | vauthors = Wu J, Dou Y, Ladiges WC | title = Adverse Neurological Effects of Short-Term Sleep Deprivation in Aging Mice Are Prevented by SS31 Peptide | journal = Clocks & Sleep | volume = 2 | issue = 3 | pages = 325–333 | date = September 2020 | pmid = 33089207 | pmc = 7573804 | doi = 10.3390/clockssleep2030024 | doi-access = free }}</ref> Studies in mice show neuronal death (in the [[hippocampus]], [[locus coeruleus]], and medial [[Prefrontal cortex|PFC]]) occurs after two days of [[Rapid eye movement sleep|REM sleep]] deprivation. However, mice do not model well the effects in humans, because they sleep a third of the duration of REM sleep of humans and [[Caspase 3|caspase-3]],  the main effector of apoptosis, kills three times the number of cells in humans than in mice.<ref>{{cite journal | vauthors = Kerr LE, McGregor AL, Amet LE, Asada T, Spratt C, Allsopp TE, Harmar AJ, Shen S, Carlson G, Logan N, Kelly JS, Sharkey J | title = Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia | journal = Cell Death and Differentiation | volume = 11 | issue = 10 | pages = 1102–1111 | date = October 2004 | pmid = 15153940 | doi = 10.1038/sj.cdd.4401449 | s2cid = 9525364 | doi-access = free }}</ref> Also not accounted for in nearly all of the studies is that acute REM sleep deprivation induces lasting (> 20 days) neuronal apoptosis in mice, and the apoptosis rate increases on the day following its end, so the amount of apoptosis is often undercounted in mice because experiments nearly always measure it the day the sleep deprivation ends.<ref>{{cite journal | vauthors = Soto-Rodriguez S, Lopez-Armas G, Luquin S, Ramos-Zuñiga R, Jauregui-Huerta F, Gonzalez-Perez O, Gonzalez-Castañeda RE | title = Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone | journal = Frontiers in Cellular Neuroscience | volume = 10 | pages = 132 | year = 2016 | pmid = 27303266 | pmc = 4884737 | doi = 10.3389/fncel.2016.00132 | doi-access = free }}</ref>  For these reasons, both the time before cells degenerate and the extent of degeneration could be greatly underevaluated in humans.

Such [[Histology|histological]] studies cannot be performed on humans for ethical reasons, but long-term studies show that sleep quality is more associated with [[gray matter]] volume reduction<ref>{{Cite web | vauthors = Haelle T | date = 3 September 2014 |title=Poor Quality Sleep May Be Linked to Shrinking Brain |url=https://www.webmd.com/sleep-disorders/news/20140903/poor-quality-sleep-may-be-linked-to-shrinking-brain | archive-url = https://web.archive.org/web/20230309202947/https://www.webmd.com/web/20230309202947/https:/www.webmd.com/sleep-disorders/news/20140903/poor-quality-sleep-may-be-linked-to-shrinking-brain | archive-date = 9 March 2023 |access-date=9 March 2023|website=WebMD |language=en}}</ref> than age,<ref>{{cite journal | vauthors = Van Someren EJ, Oosterman JM, Van Harten B, Vogels RL, Gouw AA, Weinstein HC, Poggesi A, Scheltens P, Scherder EJ | title = Medial temporal lobe atrophy relates more strongly to sleep-wake rhythm fragmentation than to age or any other known risk | journal = Neurobiology of Learning and Memory | volume = 160 | pages = 132–138 | date = April 2019 | pmid = 29864525 | doi = 10.1016/j.nlm.2018.05.017 | series = Sleep and Hippocampal Function | s2cid = 46932040 | doi-access = free | hdl = 2066/202856 | hdl-access = free }}</ref> occurring in areas like the [[precuneus]].<ref>{{cite journal | vauthors = Grau-Rivera O, Operto G, Falcón C, Sánchez-Benavides G, Cacciaglia R, Brugulat-Serrat A, Gramunt N, Salvadó G, Suárez-Calvet M, Minguillon C, Iranzo Á, Gispert JD, Molinuevo JL | title = Association between insomnia and cognitive performance, gray matter volume, and white matter microstructure in cognitively unimpaired adults | journal = Alzheimer's Research & Therapy | volume = 12 | issue = 1 | pages = 4 | date = January 2020 | pmid = 31907066 | pmc = 6945611 | doi = 10.1186/s13195-019-0547-3 | collaboration = ALFA Study | doi-access = free }}</ref>
[[File:Molecular pathway of REMSD-induced apoptosis in neurons.jpg|left|thumb|Molecular pathway of REM sleep deprivation-induced apoptosis in neurons]]
Sleep is necessary to repair cellular damage caused by [[reactive oxygen species]] and DNA damage. During long-term sleep deprivation, cellular damage aggregates up to a tipping point that triggers cellular degeneration and apoptosis.
REM sleep deprivation causes an increase in [[Norepinephrine|noradrenaline]] (which incidentally causes the person sleep deprived to be stressed) due to the neurons in the [[locus coeruleus]] producing it not ceasing to do so, which causes an increase in the activity of the [[Sodium–potassium pump|Na⁺/K⁺-ATPase pump]], which itself activates the [[Apoptosis#Intrinsic pathway|intrinsic pathway of apoptosis]]<ref>{{cite journal | vauthors = Somarajan BI, Khanday MA, Mallick BN | title = Rapid Eye Movement Sleep Deprivation Induces Neuronal Apoptosis by Noradrenaline Acting on Alpha1 Adrenoceptor and by Triggering Mitochondrial Intrinsic Pathway | journal = Frontiers in Neurology | volume = 7 | pages = 25 | date = 2016 | pmid = 27014180 | pmc = 4779900 | doi = 10.3389/fneur.2016.00025 | doi-access = free }}</ref> and prevents autophagy, which also induces the mitochondrial pathway of apoptosis.

Sleep outside of the REM phase may allow enzymes to repair brain cell damage caused by [[radical (chemistry)|free radicals]]. High metabolic activity while awake damages the enzymes themselves, preventing efficient repair. This study observed the first evidence of brain damage in rats as a direct result of sleep deprivation.<ref name="Siegel">{{cite news | vauthors = Siegel JM |title=Why We Sleep |url=http://www.semel.ucla.edu/sleepresearch/sciam2003/sciamsleep.pdf |work=[[Scientific American]] |date=November 2003 |access-date=3 April 2008 |url-status=live |archive-url=https://web.archive.org/web/20081203071459/http://www.semel.ucla.edu/sleepresearch/sciam2003/sciamsleep.pdf |archive-date=3 December 2008  }}</ref>