Unmasking Sex-Based Disparity in Neuronal Metabolism
Abstract
Both classic and emerging literature point to sex-based disparity in neuronal metabolism. While detectable under baseline conditions, this phenomenon appears to be exaggerated or sometimes unmasked in neurons by cellular stress. A complex sex-dependent response to nutrient deprivation, excitotoxicity, oxidative/nitrositive stress, oxygen-glucose deprivation, and chemical toxicity has been observed in neurons in vitro, as well as after various insults including ischemic or traumatic brain injury in vivo. Importantly, sex-based disparity in response to diverse therapeutics has been seen in neurons in culture, contemporary animal models of brain injury, and in human disease. These have clear implications for pharmacological design of therapeutics targeting central nervous system diseases involving both males and females, and preclinical testing of promising agents.
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Accumulating evidence suggests that mitochondria might perform these processes differently in males than females, both under physiological conditions and under conditions of cellular stress such as TBI.
“Accumulating evidence suggests that mitochondria might perform these processes differently in males than females, both under physiological conditions and under conditions of cellular stress such as TBI.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [116]
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“116 Under physiological conditions, sex-specific differences in mitochondrial respiration, bioenergetics, and reactive oxygen species production have been reported in both human and animal studies.”
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“Previous papers reported that neuron cultures from female rats showed more resistance to stresses than ones from male [37,38,39].”
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“However, more recently there is evidence for innate sex differences in neuronal metabolism, which may be more pronounced after injury (reviewed in (Manole et al., 2011).”
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“conditions, it appears to be magnified under pathophysiological conditions [133].”
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Guez‐Barber, D., Nicolayevsky, S. E., Johnson, K. J. D., Yun, S., & Eisch, A. J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.17.562542 · Cited by 2 · see citing works
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- Authors
- D. Manole, M., Tehranian-DePasquale, R., Du, L., Bayır, H., M. Kochanek, P., & S.B. Clark, R.
- ORCID
- Du, Lina
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-12-01
- Volume
- 17
- Issue
- 35
- Pages
- 3854-3860
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2129034858
- Cited by
- 15
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2019: 3 · 2017: 1 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (U19AI068021, AI068021)
- National Institute of Neurological Disorders and Stroke (NS 070003, R21NS070003, R01NS038620, NS38620, NS061817)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD045968, R01HD045968, K08HD058798)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- sex differences, neuronal metabolism, brain injury, ischemic brain injury, traumatic brain injury, excitotoxicity, oxidative stress, nitrosative stress, oxygen-glucose deprivation, nutrient deprivation, chemical toxicity, central nervous system therapeutics, preclinical drug testing
- MeSH terms
- Animals, Brain Injuries, Central Nervous System Diseases, Brain Ischemia, Female, Humans, Male, Synaptic Transmission, Neurons, Sex Characteristics, Oxidative Stress, Molecular Targeted Therapy
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