Post 6-OHDA lesion exposure to stress affects neurotrophic factor expression and aggravates motor impairment.
Chronic exposure to stress amplifies locomotor deficits and exacerbates dopamine neuron loss in an animal model for Parkinson's disease. The release of neurotrophic factors such as glial cell-line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) following neuronal injury attenuates exacerbated degeneration of these neurons. In this study, the neurotoxin 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle of male Sprague Dawley rats. A subset of these rats was subjected to post-lesion restraint stress after which the effect of exposure to stress on locomotor activity (forelimb akinesia test), neurotrophic factor (GDNF and NT-3) and corticosterone concentration was assessed. Exposure to post-lesion stress resulted in increased preference to use the unimpaired forelimb (forelimb ipsilateral to the lesioned hemisphere) in the forelimb akinesia test. The expected increase in both GDNF and NT-3 concentration following injury was not present in the stressed animals. However, both the non-stressed and stressed lesioned groups had decreased neurotrophic factor concentration at one and two weeks post lesion. This decrease was exaggerated in the stressed rats. The decrease in neurotrophic factor concentration was accompanied by an increase in corticosterone concentration in the stressed rats. These findings demonstrate that exposure to post-6-OHDA lesion stress exaggerates dopamine neurodegeneration and enhance motor impairment. This suggests that conditions that result in a hyper-activated hypothalamic-pituitary-adrenal axis such as depression which is concomitant to a Parkinson's disease diagnosis may be responsible for enhanced dopamine depletion by attenuating neurotrophic factor concentration elevation in the nigrostriatal pathway following neuronal injury.
University of KwaZulu-Natal College of Health Sciences, Kwazulu-Natal, Durban, South Africa. nomfundongema@yahoo.com.
Phumzile Nomfundo
PN
Ngema
University of KwaZulu-Natal College of Health Sciences, Kwazulu-Natal, Durban, South Africa.
Musa Vuyisile
MV
Mabandla
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000378:metabolism*; D009048:Motor Skills / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D016627:Oxidopamine; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D016627:Oxidopamine; D003345:Corticosterone
6-hydroxydopamine; Corticosterone; Neurotrophic factors; Parkinson’s disease; Post-lesion stress