We compared the neuroprotective effects of the catecholestrogen 2-hydroxy-estradiol (2-OH-E(2)) to the actions of 17-beta-estradiol (E(2)), since catecholestrogens have been clinically implicated in the pathophysiology of major depression and other psychiatric diseases. Using the hippocampal HT22 cell line as a well-established in vitro model system, we here show that the extent of the neuroprotective effects of 2-OH-E(2) was significantly increased compared to the physiological estrogen E(2) at equimolar concentrations after a toxic challenge with hydrogen peroxide. Statistically significant effects of neuroprotection as measured by survival of HT22 cells were detectable at concentrations of 1 and 10 microM of 2-OH-E(2) or E(2). Studies on the time-dependence of the evoked reactions showed that a pre-incubation and a post-incubation up to 30 min with a dose of 10 microM of 2-OH-E(2) resulted in a significant decrease in cell death after incubation with hydrogen peroxide if compared to E(2). Further characterization of the effects in rat brain homogenates with an assay for the induction of cellular lipid peroxidation (LPO) revealed, that 2-OH-E(2) was more effective in the reduction of LPO than E(2) in equimolar concentrations. This indicates a pharmacologically relevant effect of this hormone metabolite and a mechanism of action, which does not involve the classical estrogen receptor. In conclusion, the catecholestrogen 2-OH-E(2) induces increased neuroprotective actions in comparison to the major physiological estrogen E(2), suggesting a clinically relevant physiological function of catecholestrogens during health and disease.
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http://dx.doi.org/10.1016/s0022-3956(03)00068-2 | DOI Listing |
Metab Brain Dis
January 2025
Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Aluminium is a common metallic toxicant that easily penetrates the brain and exerts severe pathological effects e.g., oxidative stress, inflammation and neurodegeneration.
View Article and Find Full Text PDFHeliyon
December 2024
Baskent University, Faculty of Medicine, Department of Biophysics, Ankara, Türkiye.
The efficacy of MitoTEMPO, a mitochondria-targeted antioxidant, in altering nerve fiber conduction properties within the sciatic nerve of streptozotocin (STZ)-induced diabetic rats, a model for diabetic neuropathy characterized by myelinated fiber atrophy and nodal abnormalities. Utilizing the STZ-induced diabetic rat model, we assessed the impact of MitoTEMPO on nerve function through compound action potential (CAP) analysis and histological evaluation. Key indicators such as maximum depolarization (MD), CAP area, and conduction velocity distribution (CVD) were measured to gauge MitoTEMPO's neuroprotective effects, alongside physical parameters like weight and blood glucose levels.
View Article and Find Full Text PDFFront Neurosci
December 2024
Department of Anesthesiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Heliyon
January 2025
School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Baicalin and baicalein are the primary flavonoids derived from the desiccated root of , which is a member of the Lamiaceae family; these flavonoids have diverse pharmacological properties and show significant potential for the management of central nervous system disorders. Multiple studies have indicated that these substances effectively reduce the severity of illnesses such as depression, stroke, and degenerative disorders of the central nervous system by exerting antioxidant and anti-inflammatory effects, regulating programmed cell death, and reducing mitochondrial malfunction. Recent studies have highlighted the connection between the accumulation of iron and the ability of baicalein to protect the nervous system.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2025
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Neuropsychiatric disease encompasses a range of conditions resulting from various dysfunctions within the nervous system, manifesting in diverse neurological impairments. These disorders, including depression, schizophrenia, anxiety, and Alzheimer's disease, impose significant economic and psychological burdens on both individuals and society overall. Recent clinical and preclinical studies have highlighted the potential therapy of dexmedetomidine (Dex), a highly selective α2 adrenergic receptor agonist, not only as an effective sedation but also as a neuroprotective agent.
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