Early pubertal female rats are more resistant than males to
6-hydroxydopamine neurotoxicity and behavioural deficits: A possible role for
trophic factors
Affiliations: Division of Medical Physiology, University of
Stellenbosch, Western Cape, South Africa | Department of Psychology and Neurobiology, Institute
for Neuroscience, University of Texas at Austin, USA | Department of Human Biology, University of Cape Town,
South Africa
Note: [] Corresponding author: I.S. Pienaar, Department of Medical
Physiology, Faculty of Health Sciences, University of Stellenbosch, P.O. Box
19063, Tygerberg, 7505, Western Cape, South Africa. Tel.: +27 21 938 9385; Fax:
+27 21 938 9476; E-mail: ipienaar@sun.ac.za
Abstract: Purpose: The infusion of 6-hydroxydopamine (6-OHDA) into the
nigrostriatal pathway in rats is commonly used to produce an animal model of
Parkinson's disease (PD). However, most studies use male adult animals only.
The present study focused on possible gender differences in vulnerability to
6-OHDA during the early pubertal period when the effects exerted by gonadal
steroid hormones are unpronounced. Methods: Young Sprague-Dawley rats, 35
days of age, were given a low vs. a higher dose of 6-OHDA in the medial
forebrain bundle (MFB). Control rats received equivalent saline infusions. At
14 days post-surgery the rats were evaluated for forelimb akinesia. Results: For the higher dose of 6-OHDA the female rats were less impaired than
males in making adjustment steps in response to a weight shift and in a
vibrissae-evoked forelimb placing test. Tyrosine hydroxylase (TH)
immunoreactivity was significantly higher for the female rats. Conclusion: Early gender differences in cell survival factors and/or other
promoters of neuroplasticity may have contributed to the beneficial outcome in
the females. For example, NGF was found to be higher in the female rats
following administration of DA neurotoxin. It is unclear whether gonadal
steroids are involved, and if so, whether female hormones are protective or
whether male hormones are prodegenerative. Determining the mechanisms for the
improved outcome in the young female rats may lead to potential treatment
strategies in PD.
