Chisu, V., Lepore, M. G., Zedda, M. & Farina, V. Testosterone induces neuroprotection from oxidative stress. Effects on catalase activity and 3-Nitro-L-styrosine incorporation into -tubulin in a mouse neuroblastoma cell line. Arch. Ital. Biol. 144, 63-73

Department of Animal Biology, University of Sassari.
Archives italiennes de biologie (Impact Factor: 1.49). 06/2006; 144(2):63-73. DOI: 10.4449/aib.v144i2.882
Source: PubMed


3-nitro-L-tyrosine is formed by nitric oxide following different pathways such as NADPH oxidase, xanthine oxidase or glutamate NMDA receptor activation and is involved in the pathology of different neurological disorders. Unlike estradiol, a neuroprotective role of androgens against oxidative cell injury has not been fully investigated. This work targets the possible effects of testosterone on neuroblastoma cells exposed to 3-nitro-L-tyrosine. C1300 mouse undifferentiated neuroblastoma cells exposed to 3-nitro-L-tyrosine were cultured in the presence of testosterone. Morphological examination, proliferation and nuclear viability assays were performed. The expression of tyrosinated alpha-tubulin and incorporation of 3-nitro-L-tyrosine into protein were also estimated. Cells exposed to 3-nitro-L-tyrosine showed globular shape, reduced cytoplasmic processes and growth inhibition in comparison with controls. When testosterone was added to the medium, these changes were not evident. In addition, testosterone induced an upregulation of tyrosinated alpha-tubulin, a marker of neuronal plasticity, and a decrease in 3-nitro-L-tyrosine incorporation into tubulin. Our results suggest that testosterone exposure can diminish 3-nitro-L-tyrosine toxic effects on the morphology and growth rate of neuroblastoma cells. The upregulation of tyrosinated alpha-tubulin in testosterone-exposed cells would be consistent with concurrent plasticity events. Failure in alpha-tubulin nitration detected in cells exposed to both 3-nitro-L-tyrosine and testosterone, may support the idea that testosterone interferes with 3-nitro-L-tyrosine protein incorporation. Moreover, testosterone-induced neuroprotection likely entails a linkage with the androgen receptor as is suggested by the flutamide-induced inhibition of the hormone activity. Finally, the neuroprotective effects of testosterone in neuroblastoma cells could deal with the cellular antioxidant defence system, as shown by testosterone-induced increase in catalase activity.

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    • "After administration of TES or MP, CAT levels increased significantly revealing the antioxidant activity of both drugs. Also, previous studies demonstrated the antioxidant activity of TES [10] [19] [54] [57]. Furthermore, XO is another important source of reactive oxygen species [58]. "
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    ABSTRACT: Aim: Previous studies demonstrated the neuroprotective effects of testosterone, but no previous study has examined the neuroprotective effects of testosterone on spinal cord ischemia/reperfusion injury. The purpose of this study was to evaluate whether testosterone could protect the spinal cord from ischemia/reperfusion injury. Methods: Rabbits were randomised into four groups of eight animals as follows: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (testosterone). In the control group only a laparotomy was performed. In all other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Levels of malondialdehyde and catalase were analysed, as were the activities of caspase-3, myeloperoxidase, and xanthine oxidase. Histopathological and ultrastructural evaluations were performed. Neurological evaluation was performed with the Tarlov scoring system. Results: After ischemia-reperfusion injury, increases were found in caspase-3 activity, myeloperoxidase activity, malondialdehyde levels, and xanthine oxidase activity. In contrast, decreases in catalase levels were observed. After the administration of testosterone, decreases were observed in caspase-3 activity, myeloperoxidase activity, malondialdehyde levels, and xanthine oxidase activity, whereas catalase levels increased. Furthermore, testosterone treatment showed improved results concerning histopathological scores, ultrastructural score and Tarlov scores. Conclusions: Our results revealed for the first time that testosterone exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.
    Injury 11/2014; 46(2). DOI:10.1016/j.injury.2014.11.002 · 2.14 Impact Factor
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    • "However, evidence for a causal relationship between T release and cognitive functioning is still missing. Such an association might be assumed as T has shown to have a neuroprotective role in the central nervous system (reviewed by Bialek, Zaremba, Borowicz, & Czuczwar, 2004; Chisu et al., 2006). T receptors have been found in cortex regions and the hippocampus (e.g., Beyenburg et al., 2000; Goldstein et al., 2001). "
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    ABSTRACT: We investigated whether the chronic physical activity participation had an impact on the acute effects of a short bout of 12 min of intensive physical activity on cognitive performance and testosterone con-centration in primary school students (n = 42, mean age = 9.69, SD ¼ .44; experimental group (EG), n = 27; control group (CG), n = 15). Furthermore, we looked for associations between testosterone concentration and cognitive performance. After the intervention, participants of the EG showed better cognitive performances as compared to the CG. We further observed a significant group (EG, CG) x test (pre, post) x activity level (high, low) interaction. Post hoc pairwise comparisons revealed that after acute physical activity the testosterone concentration was diminished only in habitually low active children. The results indicate that intensive physical activity only attenuates the reactivity of the hypothalamic-pituitary-gonadal axis in habitually low active preadolescents, but had a beneficial effect on cognitive performance for all participants independent of their physical activity level and testosterone.
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    • "However, solid diagnostic criteria of cortisol insufficiency in critical illness are still lacking and under debate [7,8]. Furthermore, the known roles of GH, IGF-1, estrogen and testosterone upon brain function and plasticity propose that inadequate levels after sTBI may have both acute and long-term significance upon the recovering brain [9-13]. GH and IGF-1 receptors are abundant in the brain, GH is involved in vascular reactivity, vascular tone and CNS repair processes, while IGF-1 seems to be important in re-myelination and avoidance of demyelination [11,12,14]. "
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    ABSTRACT: Object The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome. Methods Prospective study, including consecutive patients, 15–70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08–10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17–19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E. Results Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH- and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated. Conclusion Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.
    Scandinavian Journal of Trauma Resuscitation and Emergency Medicine 04/2013; 21(1):33. DOI:10.1186/1757-7241-21-33 · 2.03 Impact Factor
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