Abstract
Sex differences in brain physiology and by inference various pathologies are generally recognized, however frequently ignored in epidemiological and experimental studies, leading to numerous data gaps. As a consequence, the mechanisms underlying sexual dimorphism of neurological diseases remain largely unknown. Several cellular and molecular pathways linked to the etiology and pathogenesis of various brain disorders have been recently described as sex-specific. Here, we review the evidence for sex differences in brain redox homeostasis, which is an important factor in brain physiology and disease. First, we focus on sex-specific differences in the healthy brain regarding popular redox balance markers, including reactive oxygen and nitrogen species, oxidative damage, and antioxidant status. We also review the modulatory effect of steroid sex hormones on these markers. Lastly, we approach the sex-specific changes in brain redox homeostasis in disease and discuss the possibility that differential redox response contributes to the sexual dimorphism of neurological disorders.
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Abbreviations
- AA:
-
Ascorbic acid
- Aβ:
-
β-Amyloid peptide
- AD:
-
Alzheimer disease
- ADHD:
-
Attention deficit hyperactivity disorder
- ALS:
-
Amyotrophic lateral sclerosis
- AP-1:
-
Activator protein-1
- APP:
-
Amyloid precursor protein
- ARE:
-
Antioxidant response element
- As:
-
Arsenic
- ASD:
-
Autism spectrum disorder
- ATP:
-
Adenosine triphosphate
- BOAA:
-
β-N-Oxalyl-amino-L-alanine
- BPA:
-
Bisphenol A
- CAT:
-
Catalase
- CB:
-
Cerebrum
- CCI:
-
Controlled cortical impact
- CN:
-
Caudate nucleus
- CNS:
-
Central nervous system
- COX:
-
Cytochrome c oxidase
- CP:
-
Caudate putamen
- CPF:
-
Chlorpyrifos
- CREB:
-
Cyclic AMP response element binding protein
- CSF:
-
Cerebrospinal fluid
- CV:
-
Cerebellum
- CX:
-
Cortex
- DBL:
-
Lewy body dementia
- DE:
-
Diesel exhaust
- DHT:
-
Dihydrotestosterone
- E2:
-
17β-estradiol
- ED:
-
Embryonic day
- EDC:
-
Endocrine disrupting chemical
- ER:
-
Estrogen receptor
- ETC:
-
Electron transport chain
- EtOH:
-
Ethanol
- EW:
-
Ethanol withdrawal
- F2-IsoP:
-
F2-isoprostane
- FALS:
-
Familial ALS
- FC:
-
Frontal cortex
- Fe:
-
Iron
- FMO:
-
Flavin-containing monooxygenase
- FRAP:
-
Ferric reducing antioxidant power
- GCL:
-
Glutamate-cysteine ligase
- GDX:
-
Gonadectomy
- γGT:
-
γ-Glutamyl transferase
- GSH:
-
Glutathione reduced
- GSSH:
-
Glutathione oxidized
- GPX:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- GRX:
-
Glutaredoxin
- GS:
-
Glutathione synthase
- GST:
-
Glutathione S-transferase
- Hcy:
-
Homocysteine
- HD:
-
Huntington’s disease
- HI:
-
Hypoxia-ischemia
- HIE:
-
Hypoxic-ischemic encephalopathy
- 4-HNE:
-
4-hydroxynonenal
- HO-1:
-
Heme oxygenase 1
- HP:
-
Hippocampus
- HT:
-
Hypothalamus
- ICH:
-
Intracerebral hemorrhage
- iNOS:
-
Inducible nitric oxide synthase
- IQ:
-
Intelligence quotient
- KEAP 1:
-
Kelch-like ECH-associated protein 1
- KI:
-
Knock-in
- LPO:
-
Lipid peroxidation
- MB:
-
Midbrain
- MCAO:
-
Middle cerebral artery occlusion
- MDD:
-
Major depressive disorder
- MeHg:
-
Methylmercury
- Mn:
-
Manganese
- MO:
-
Medulla oblongata
- MPP+ :
-
1-methyl-4-phenylpyridinium
- MPTP:
-
1-methyl-4-phenyl-1, 2, 3, 6, tetrahydro-pyridine
- NA:
-
Nucleus accumbens
- NADH/NAD:
-
Nicotinamide adenine dinucleotide
- NF-κB:
-
Nuclear factor-κB
- NIH:
-
National Institutes of Health
- nNOS:
-
Neuronal nitric oxide synthase
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- NOx:
-
Stable nitric oxide metabolites, nitrite (NO2-) + nitrate (NO3-)
- NRF2:
-
Nuclear factor erythroid 2-related factor 2
- 3-NT:
-
3-nitrotyrosine
- NQO1:
-
NAD(P)H dehydrogenase (quinone) 1
- OB:
-
Olfactory bulb
- 6-OHDA:
-
6-hydroxydopamine
- ONS:
-
Oxidative -nitrosative stress
- OP:
-
Organophosphate pesticide
- OVX:
-
Ovariectomy
- PCB:
-
Polychlorinated biphenyl
- PD:
-
Parkinson disease
- PFAS:
-
Poly- and perfluoroalkyl substances
- PFC:
-
Prefrontal cortex
- PFOA:
-
Perfluorooctanoic acid
- PFOS:
-
Perfluorooctane sulfonate
- PND:
-
Postnatal day
- Poly(I:C):
-
Polyinosinic/polycytidylic acid
- PON:
-
Paraoxonase
- PROG:
-
Progesterone
- PRX:
-
Peroxiredoxin
- PUS:
-
Peripubertal unpredictable stress
- rNPCs:
-
Rat neural progenitor cells
- RNS:
-
Reactive nitrogen species
- ROS:
-
Reactive oxygen species
- SCZ:
-
schizophrenia
- SE:
-
status epilepticus
- SN:
-
substantia nigra
- SOD:
-
Superoxide dismutase
- SOD1:
-
Cu/Zn-superoxide dismutase
- SOD2:
-
Mn-superoxide dismutase
- ST:
-
Striatum
- TAC:
-
Total antioxidant capacity
- TBARS:
-
Thiobarbituric acid reactive substances
- TBBPA:
-
Tetrabromobisphenol A
- TBI:
-
Traumatic brain injury
- TCDD:
-
2,3,7,8-tetrachlorodibenzo-p-dioxin
- TEST:
-
Testosterone
- Tg:
-
Transgenic
- TRX:
-
Thioredoxin
- TRXR:
-
Thioredoxin reductase
- TP:
-
Testosterone propionate
- UA:
-
Uric acid
- VDR:
-
Vitamin D receptor
- wt:
-
Wild-type
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MA was supported by grants from the National Institute of Environmental Health Sciences, NIEHS R01ES07331, NIEHS R01ES10563, and NIEHS R01ES020852.
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Ruszkiewicz, J.A., Miranda-Vizuete, A., Tinkov, A.A. et al. Sex-Specific Differences in Redox Homeostasis in Brain Norm and Disease. J Mol Neurosci 67, 312–342 (2019). https://doi.org/10.1007/s12031-018-1241-9
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Keywords
- Oxidative stress
- Antioxidant
- Sex
- Brain
- Neurodegeneration
- Neurotoxicity