Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons
Open accessAbstract
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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“…mushroom spines are thought to indicate mature synapses (Hering and Sheng, 2001), more mushroom spines are likely indicative of more synaptic input (Matsuzaki et al., 2001), which may contribute to the higher orexin system activation in females that we observed in previous studies (Grafe et al.,…”
ResultDendritic spines: from structure to in vivo function
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Sex differences in stress regulation of arousal and cognition
Bangasser, D. A., Eck, S. R., Telenson, A. M., & Salvatore, M. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.09.025 · Cited by 133 · see citing works
Effects of Traumatic Brain Injury on the Orexin/Hypocretin System
Somach, R. T., Lim, M. M., & Cohen, A. S. (2025) · Neurotrauma Reports · doi:10.1089/neur.2024.0111 · Cited by 2 · see citing works
- 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)
- PMC
- PMC6922092
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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