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Journal Article 2013; 34(5): 395-401 PubMed PMID: 23922037 Citation  Keywords:  Aging:metabolism, Animals, Cerebral Cortex:cytology, DNA Topoisomerases, Type II:genetics, DNA-Binding Proteins:genetics, Neurons:cytology, Neuroprotective Agents:pharmacology, Sheep, Testosterone:pharmacology, Tyrosine:analogs & derivatives, Up-Regulatio.   

OBJECTIVE: This research reports the expression of topoisomerase βII in fetal sheep neuronal cells. The β isoform of DNA topoisomerase II plays a role in DNA repair process in non proliferating cells as neurons and its expression tends to be downregulated with senescence.

METHODS: Cortical neurons from 60-day-old sheep embryos underwent two protocols: the former based on rising time of culture (10, 20 and 30 days); the latter based on the 72hrs exposure to 3-nitro-L-tyrosine (oxidative/nitrosative stressor) and/or testosterone.

RESULTS: Our results showed an increase in β-galactosidase activity and, in contrast, a reduction in topoisomerase βII expression with time (first protocol). The exposure of sheep primary neurons to 3-nitro-L-tyrosine led to an upregulation of βII topoisomerase expression to be likely seen as a reaction to nitrosative stress. Testosterone addition to 3-nitro-L-tyrosine-exposed cells results in topoisomerase βII decrease possibly due to the neuroprotective properties of testosterone (second protocol). No significant variations in the marker of aging β-galactosidase were observed in the cells exposed to 3-nitro-L-tyrosine and testosterone.

CONCLUSION: The protocol based on time could be of some interest as a model of neuronal senescence in vitro. Topoisomerase βII decrease with aging likely indicates a reduced ability to repair DNA during neuronal senescence. In contrast, the second protocol may not be seen as a reliable model of aging since 3-nitro-L-tyrosine does not lead to a topoisomerase βII decrease. Testosterone was able to cope with oxidative/nitrosative damage, allowing cells to reduce their needs in DNA repair which in turn leads to a downregulation of topoisomerase IIβ expression....

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Comparative Study 2005; 26(2): 121-124 PubMed PMID: 15855882 Citation  Keywords:  Animals, Exploratory Behavior:drug effects, Female, Habituation, Psychophysiologic:drug effects, Male, Motor Activity:drug effects, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Sex Factors, Testosterone:pharmacology, Vocalization, Animal:drug effec.   

OBJECTIVES: The purpose of the present study was to characterize the influence of testosterone administered to pregnant females on offsprings postnatal behavioral strategies in the open field.

METHODS: The influence of maternal testosterone on behaviour of 23 day old male and female offsprings was studied in a 20-minute open field test. A total of 9 behavioural events were compared between a control (male n=12, female n=8) and a testosterone group (male n=9, female n=9). Dynamics and patterns of association of these behavioural events were analyzed. The testosterone group was prenatally exposed to testosterone (a single intramuscular injection of 2.5 mg testosteroni isobutyras on gestation day 14).

RESULTS: Male offsprings exposed prenatally to testosterone displayed significantly high levels of ambulation (P<0.05), sniffing (P<0.01), sniffing the air (P<0.05), urination (P<0.05) and significantly lower level of vocalization (P<0.05) than control. Female offsprings exposed prenatally to testosterone displayed significantly higher level of sniffing the air (P<0.05) than control. Significant differences in the dynamics of habituation process were registered only in the group of male. They were from 5 to 10 min in ambulation (P<0.05), from 10 to 15 min in sniffing (P<0.05) and vocalization (P<0.05), from 10 to 15 min and from 15 to 20 min in sniffing the air (P<0.05) and from 0 to 5 min in defecation (P<0.05) and urination (P<0.01).

CONCLUSION: Our results suggest that maternal testosterone may influence especially male postnatal open field strategies....

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