Early pubertal female rats are more resistant than males to 6-hydroxydopamine neurotoxicity and behavioural deficits: a possible role for trophic factors.
OBJECTIVE
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.


CONCLUSIONS
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.
Pienaar
I S
IS
Division of Medical Physiology, University of Stellenbosch, Western Cape, South Africa. ipienaar@sun.ac.za
Schallert
T
T
Russell
V A
VA
Kellaway
L A
LA
Carr
J A
JA
Daniels
W M U
WM
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D001523:Mental Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D016627:Oxidopamine / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014738:Vibrissae / Q000187:drug effects / Q000294:innervation
D009498:Neurotoxins; D016627:Oxidopamine; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase