Cited by 25Sleep and Wakefulness ResearchStress Responses and CortisolNeuroscience and Neuropharmacology Research

Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons

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Grafe, Laura A., Geng, Eric, Corbett, Brian, Urban, Kimberly, Bhatnagar, Seema·2019·Neuroscience

Abstract

We recently found that non-stressed female rats have higher basal prepro-orexin expression and activation of orexinergic neurons compared to non-stressed males, which lead to impaired habituation to repeated restraint stress at the behavioral, neural, and endocrine level. Here, we extended our study of sex differences in the orexin system by examining spine densities and dendritic morphology in putative orexin neurons in adult male and female rats that were exposed to 5 consecutive days of 30-min restraint. Analysis of spine distribution and density indicated that putative orexinergic neurons in control non-stressed females had significantly more dendritic spines than those in control males, and the majority of these were mushroom spines. This morphological finding may suggest more excitatory input onto orexin neurons in female rats. As orexin neurons are known to promote the hypothalamic-pituitary-adrenal response, this morphological change in orexin neurons could underlie the impaired habituation to repeated stress in female rats. Dendritic complexity did not differ between non-stressed males and females, however repeated restraint stress decreased total dendritic length, nodes, and branching primarily in males. Thus, reduced dendritic complexity of putative orexinergic neurons is observed in males but not in females after 5days of repeated restraint stress. This morphological change might be reflective of decreased orexin system function, which may allow males to habituate more fully to repeated restraint than females. These results extend our understanding of the role of orexin neurons in regulating habituation and demonstrate changes in putative orexin cell morphology and spines that may underlie sex differences in habituation.

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  • Previous research has shown that orexin neurons in males and females have differences in response to stress and disease.

    “Previous research has shown that orexin neurons in males and females have differences in response to stress and disease.110–112”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [111]

    The Discussion reports sex-dependent differences in putative orexin-neuron structure after repeated restraint stress in male and female rats. The Introduction says orexin levels are altered in stress-related disorders and those disorders differ in prevalence by sex, but it does not establish that orexin neurons in males and females respond differently to disease. No page numbers are available in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Grafe, L. A., Geng, E., Corbett, B., Urban, K., & Bhatnagar, S.
Affiliations
  • Bryn Mawr College (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Bhatnagar, Seema
Venue
Neuroscience
Publisher
Elsevier BV
Published
2019-10
Volume
418
Pages
266-278
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2969804097
Cited by
25
References
7
Citations by year
2025: 3 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 1 · 2019: 1 · 2017: 1
FWCI
1.74
Type
journal article
Language
en
Open access
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Scholarship, Research, and Creative Work at Bryn Mawr College (Bryn Mawr College) (submittedVersion)
Funders
National Institute of Mental Health
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
orexin neurons, sex differences, restraint stress, dendritic morphology, dendritic spines, spine density, mushroom spines, dendritic complexity, hypothalamic-pituitary-adrenal axis, female rats
MeSH terms
Orexins, Animals, Female, Male, Pituitary-Adrenal System, Restraint, Physical, Sex Characteristics, Stress, Psychological, Dendritic Spines, Orexin Receptors

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