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The Statin Target H...
The Statin Target HMG-Coenzyme a Reductase (Hmgcr) Regulates Sleep Homeostasis in Drosophila
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- Alsehli, Ahmed M. (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi,King Abdulaziz Univ & Hosp, Fac Med, Al Ehtifalat St, Jeddah 21589, Saudi Arabia.
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- Liao, Sifang (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Al-Sabri, Mohamed H. (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Vasionis, Lukas (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Purohit, Archana (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Behare, Neha (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Clemensson, Laura Emily (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Williams, Michael J. (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi
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- Schiöth, Helgi B. (författare)
- Uppsala universitet,Schiöth: Funktionell farmakologi,Sechenov First Moscow State Med Univ, Sechenov Biomed Sci & Technol Pk, Inst Translat Med & Biotechnol, Trubetskay Str 8, Moscow 119991, Russia.
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(creator_code:org_t)
- 2022-01-10
- 2022
- Engelska.
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:1
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Statins, HMG Coenzyme A Reductase (HMGCR) inhibitors, are a first-line therapy, used to reduce hypercholesterolemia and the risk for cardiovascular events. While sleep disturbances are recognized as a side-effect of statin treatment, the impact of statins on sleep is under debate. Using Drosophila, we discovered a novel role for Hmgcr in sleep modulation. Loss of pan-neuronal Hmgcr expression affects fly sleep behavior, causing a decrease in sleep latency and an increase in sleep episode duration. We localized the pars intercerebralis (PI), equivalent to the mammalian hypothalamus, as the region within the fly brain requiring Hmgcr activity for proper sleep maintenance. Lack of Hmgcr expression in the PI insulin-producing cells recapitulates the sleep effects of pan-neuronal Hmgcr knockdown. Conversely, loss of Hmgcr in a different PI subpopulation, the corticotropin releasing factor (CRF) homologue-expressing neurons (DH44 neurons), increases sleep latency and decreases sleep duration. The requirement for Hmgcr activity in different neurons signifies its importance in sleep regulation. Interestingly, loss of Hmgcr in the PI does not affect circadian rhythm, suggesting that Hmgcr regulates sleep by pathways distinct from the circadian clock. Taken together, these findings suggest that Hmgcr activity in the PI is essential for proper sleep homeostasis in flies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
Nyckelord
- statins
- hmgcr
- insulin
- sleep
- sleep deprivation
- mevalonate pathway
- circadian rhythm
- DH44
- corticotropin releasing factor
- Drosophila
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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