Related Experiment Video

Updated: Jan 5, 2026

A Chronic Sleep Fragmentation Model using Vibrating Orbital Rotor to Induce Cognitive Deficit and Anxiety-Like Behavior in Young Wild-Type Mice
06:23

A Chronic Sleep Fragmentation Model using Vibrating Orbital Rotor to Induce Cognitive Deficit and Anxiety-Like Behavior in Young Wild-Type Mice

Published on: September 22, 2020

5.9K

Hypothalamic orexin and mechanistic target of rapamycin activation mediate sleep dysfunction in a mouse model of

Bo Zhang1, Dongjun Guo1, Lirong Han1

  • 1Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

Neurobiology of Disease
|October 13, 2019
PubMed

Insights

Tuberous sclerosis complex (TSC) causes sleep problems due to mTOR pathway overactivation. Targeting mTOR or orexin pathways with drugs like rapamycin or suvorexant can restore normal sleep patterns in TSC mouse models.

Area of Science:

  • Neuroscience
  • Genetics
  • Sleep Medicine

Background:

  • Tuberous sclerosis complex (TSC) is a genetic disorder characterized by mTOR pathway hyperactivation.
  • TSC often presents with neurological symptoms, including epilepsy and sleep disturbances.
  • The precise mechanisms underlying sleep dysfunction in TSC remain unclear.

Purpose of the Study:

  • To investigate the mechanisms of sleep dysfunction in a mouse model of TSC.
  • To explore the role of the mTOR pathway and orexin in TSC-related sleep disorders.
  • To evaluate potential therapeutic interventions for sleep abnormalities in TSC.

Main Methods:

  • Utilized a conditional knockout mouse model (Tsc1GFAPCKO) with Tsc1 gene inactivation in neurons and astrocytes.
  • Conducted sleep studies using EEG, EMG, and behavioral analysis.
  • Assessed mTOR activity and orexin expression in hypothalamic tissues and neurons.
  • Administered rapamycin (mTOR inhibitor) and suvorexant (orexin antagonist) to evaluate their effects on sleep.

Main Results:

  • Tsc1GFAPCKO mice exhibited reduced REM sleep and impaired sleep-wake cycle regulation.
  • Increased mTOR activity and orexin expression were observed in the hypothalamus of Tsc1GFAPCKO mice.
  • Rapamycin treatment normalized sleep abnormalities and reduced orexin levels, confirming mTOR dependence.
  • Suvorexant treatment restored normal REM sleep levels in Tsc1GFAPCKO mice.

Conclusions:

  • Identified a novel mechanistic link between mTOR hyperactivation and orexin dysregulation in the hypothalamus contributing to sleep dysfunction in TSC.
  • Demonstrated that targeting the mTOR and orexin pathways can ameliorate sleep disturbances in a TSC mouse model.
  • Suggests potential therapeutic strategies for managing sleep disorders in individuals with TSC.
Keywords:
MiceOrexinRapamycinSeizureSleepTuberous sclerosis

More Related Videos

Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice08:58

Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice

Published on: June 19, 2019

10.4K
Noninvasive, High-throughput Determination of Sleep Duration in Rodents07:33

Noninvasive, High-throughput Determination of Sleep Duration in Rodents

Published on: April 18, 2018

8.2K

Related Concept Videos

Sleep-Wake Cycles01:24

Sleep-Wake Cycles

Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and  rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
2.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Narcolepsy01:07

Narcolepsy

Narcolepsy is a chronic sleep disorder characterized by pervasive, uncontrolled sleepiness and other sleep disturbances. One of its hallmark symptoms is an abrupt transition to REM sleep upon falling asleep, which causes symptoms typically associated with this phase to occur unexpectedly during wakefulness. These include the following symptoms, which typically last from a minute or two to half an hour.
453
Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.5K
Understanding Sleep01:11

Understanding Sleep

Sleep, an essential biological state, involves significant reductions in physical activity, sensory awareness, and interaction with the environment. This complex physiological process is primarily regulated by specific brain regions, notably the hypothalamus and pons, which govern the sleep-wake cycle or circadian rhythm.
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...
1.4K