Administration of testosterone attenuates neuronal loss following axotomy in the brain-stem motor nuclei of female rats.
This study was undertaken to elucidate whether (1) administration of testosterone to female rats attenuates axotomy-induced neuronal loss; (2) the efficacy of testosterone treatment is related to the age of animals, the dosage given, and the time and duration of the treatment; (3) neurons which project or terminate aberrantly can survive; and (4) the trophic actions of testosterone on neuronal survival and axonal outgrowth are operated under the same mechanisms. The hypoglossal and facial nerves were transected unilaterally at 3 and 6 weeks of age. In order to establish the dose-response curve, testosterone propionate (TP) at doses of 0.5, 1.0, 2.0, or 5.0 mg was injected subcutaneously twice weekly during the first 4 postaxotomy weeks, and once weekly thereafter for an additional 6 weeks. Neuronal numbers in the hypoglossal and facial motor nuclei were counted 10-12 weeks after axotomy in serial paraffin sections stained with cresyl violet. To determine the time course of TP effect, neuronal numbers were counted at 1, 4, 12, and 20 weeks after axotomy. In addition, neuronal loss 12 weeks after axotomy in rats treated with TP for the first 3 postaxotomy weeks only was compared with that in rats withheld TP treatment until the 5th postaxotomy week. To determine axonal projections and terminations of the surviving neurons, HRP retrograde tracing technique was used. Results indicated that TP treatment significantly attenuated neuronal loss in prepubertal and young adult female rats in a dose- and time-dependent manner. Only doses which elevated serum testosterone to levels comparable to or surpassing normal male levels were effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Yu
W H
WH
Department of Cell Biology and Anatomical Sciences, City University of New York Medical School, New York 10031.
D000818:Animals; D001369:Axons / Q000502:physiology; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D005260:Female; D006735:Horseradish Peroxidase; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D013739:Testosterone; D006735:Horseradish Peroxidase