Cited by 13Sleep and Wakefulness ResearchTraumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury Research
Mild Traumatic Brain Injury Affects Orexin/Hypocretin Physiology Differently in Male and Female Mice
Open accessSomach, Rebecca T., Jean, Ian D., Farrugia, Anthony M., Cohen, Akiva S.·2023·Journal of Neurotrauma
DOI 10.1089/neu.2023.0125PMC PMC10701510
Abstract
Traumatic brain injury (TBI) is known to affect the physiology of neural circuits in several brain regions, which can contribute to behavioral changes after injury. Disordered sleep is a behavior that is often seen after TBI, but there is little research into how injury affects the circuitry that contributes to disrupted sleep regulation. Orexin/hypocretin neurons (hereafter referred to as orexin neurons) located in the lateral hypothalamus normally stabilize wakefulness in healthy animals and have been suggested as a source of dysregulated sleep behavior. Despite this, few studies have examined how TBI affects orexin neuron circuitry. Further, almost no animal studies of orexin neurons after TBI have included female animals. Here, we address these gaps by studying changes to orexin physiology using ex vivo acute brain slices and whole–cell patch clamp recording. We hypothesized that orexin neurons would have reduced afferent excitatory activity after injury. Ultimately, this hypothesis was supported but there were additional physiological changes that occurred that we did not originally hypothesize. We studied physiological properties in orexin neurons approximately 1 week after mild traumatic brain injury (mTBI) in 6–8-week-old male and female mice. mTBI was performed with a lateral fluid percussion injury between 1.4 and 1.6 atmospheres. Mild TBI increased the size of action potential afterhyperpolarization in orexin neurons from female mice, but not male mice and reduced the action potential threshold in male mice, but not in female mice. Mild TBI reduced afferent excitatory activity and increased afferent inhibitory activity onto orexin neurons. Alterations in afferent excitatory activity occurred in different parameters in male and female animals. The increased afferent inhibitory activity after injury is more pronounced in recordings from female animals. Our results indicate that mTBI changes the physiology of orexin neuron circuitry and that these changes are not the same in male and female animals.
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There was an increase in afferent GABAergic activity onto orexin neurons after TBI.
“We also found that there was an increase in afferent GABAergic activity onto orexin neurons”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [83]
There was reduced glutamatergic activity in orexin neurons after TBI, measured by whole-cell patch clamp electrophysiology.
“We followed this result and found reduced glutamatergic activity in orexin neurons by measuring afferent input using whole-cell patch clamp electrophysiology.83”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [83]
Another study found that male and female animals had differences in orexin neuron physiology after injury and that inhibitory activity might be more prominent in orexin neurons in females after injury.
“Another study found that male and female animals had differences in orexin neuron physiology after injury and that inhibitory activity might be more prominent in orexin neurons in females after injury.83”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [83]
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- Authors
- Somach, R. T., Jean, I. D., Farrugia, A. M., & Cohen, A. S.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Cohen, Akiva S.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2023-09-29
- Volume
- 40
- Issue
- 19-20
- Pages
- 2146-2163
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC10701510
- OpenAlex
- W4384926040
- Cited by
- 13
- References
- 95
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Children's Hospital of Philadelphia
- University of Pennsylvania
- University of Texas Southwestern Medical Center
- National Institutes of Health
- Intellectual and Developmental Disabilities Research Center (P50HD105354)
- National Heart, Lung, and Blood Institute (T32HL007953)
- National Institute of Neurological Disorders and Stroke (R01NS120099)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD059288, P50HD105354)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- mild traumatic brain injury, orexin neurons, orexin, sex differences, lateral hypothalamus, sleep regulation, wakefulness, action potential threshold, lateral fluid percussion injury, neural circuits
- MeSH terms
- Orexins, Brain Injuries, Traumatic, Animals, Brain, Brain Concussion, Female, Male, Neurons, Sleep, Wakefulness, Mice
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