Effect of sex and autism spectrum disorder on oxytocin receptor binding and mRNA expression in the dopaminergic pars compacta of the human substantia nigra
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Abstract Oxytocin is an endogenous neuropeptide hormone that influences social behaviour and bonding in mammals. Variations in oxytocin receptor (OXTR) expression may play a role in the social deficits seen in autism spectrum disorder. Previous studies from our laboratory found a dense population of OXTR in the human substantia nigra (SN), a basal ganglia structure in the midbrain that is important in both movement and reward pathways. Here, we explore whether differences in OXTR can be identified in the dopaminergic SN pars compacta of individuals with autism. Postmortem human brain tissue specimens were processed for OXTR autoradiography from four groups: males with autism, females with autism, typically developing (TD) males and TD females. We found that females with autism had significantly lower levels of OXTR than the other groups. To examine potential gene expression differences, we performed in situ hybridization in adjacent slides to visualize and quantify OXTR mRNA as well as mRNA for tyrosine hydroxylase. We found no differences in mRNA levels for either gene across the four groups. These results suggest that a dysregulation in local OXTR protein translation or increased OXTR internalization/recycling may contribute to the differences in social symptoms seen in females with autism. This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.
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A decrease in OXTR binding has been identified in postmortem brain samples from females with ASD.
“Notably, a decrease in OXTR binding has been identified in postmortem brain samples from females with ASD (Frehner et al., 2022).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Frehner et al., 2022
Males with ASD did not display significant changes in OXTR binding, raising the possibility of a sex-related distinction in the regulation of mature OXTR levels.
“Interestingly, males with ASD did not display significant changes in OXTR binding, raising the possibility of a sex-related distinction in the regulation of mature OXTR levels.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Frehner et al., 2022
Additional investigations employing in situ hybridization techniques to visualise and quantify OXTR and TH mRNA have yielded results indicating no significant alterations.
“Furthermore, additional investigations employing in situ hybridization techniques to visualise and quantify OXTR and TH mRNA have yielded results indicating no significant alterations.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Frehner et al., 2022
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- Authors
- Frehner, S. S., Dooley, K. T., Palumbo, M. C., Smith, A. L., Goodman, M. M., Bales, K. L., & Freeman, S. M.
- Affiliations
- Utah State University (US)
- Oregon Health & Science University (US)
- Emory University (US)
- University of California, Davis (US)
- Corresponding author
- Freeman, Sara M.
- Venue
- Philosophical Transactions of the Royal Society B
- Publisher
- The Royal Society
- Published
- 2022-07-11
- Volume
- 377
- Issue
- 1858
- Pages
- 20210118-20210118
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC9272142
- OpenAlex
- W4285011874
- Cited by
- 18
- References
- 53
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 1
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- oxytocin receptor, autism spectrum disorder, substantia nigra, pars compacta, dopaminergic neurons, sex differences, social dysfunction, tyrosine hydroxylase, receptor internalization, postmortem brain
- MeSH terms
- Autism Spectrum Disorder, Animals, Female, Humans, Male, Mammals, Oxytocin, RNA, Messenger, Substantia Nigra, Receptors, Oxytocin, Pars Compacta
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