Differences in dopaminergic neuroprotective effects of estrogen during estrous cycle.
Previous studies suggest that estrogen treatment protects nigrostriatal dopaminergic neurons, but have not examined whether the changes in estrogen levels during estrous cycle can influence the susceptibility of these neurons to neurotoxins. Here we show that the loss of dopaminergic neurons in the substantia nigra was greater in animals lesioned at diestrus (low estrogen) using 6-hydroxydopamine or buffered iron chloride, when compared with animals lesioned at proestrus (high estrogen). Lesioning at diestrus with 6-hydroxydopamine reduced the striatal dopamine content, whereas the dopamine content was preserved in animals lesioned at proestrus. The density of the dopamine transporter, upon which 6-hydroxydopamine toxicity is dependent, was lower when circulating estrogen was high. These results thus support a neuroprotectory role for estrogen.
Datla
Krishna P
KP
Parkinson's Disease Research Unit, Department of Neurinflammation, Imperial College of Science, Technology and Medicine, Charing Cross Campus, London, UK.
Murray
Hilary E
HE
Pillai
Arani V
AV
Gillies
Glenda E
GE
Dexter
David T
DT
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D002712:Chlorides; D004031:Diestrus; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004958:Estradiol / Q000032:analysis; D004967:Estrogens / Q000502:physiology*; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity; D005609:Free Radicals; D006719:Homovanillic Acid / Q000032:analysis; D007267:Injections; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D011359:Proestrus; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
D002712:Chlorides; D050483:Dopamine Plasma Membrane Transport Proteins; D004967:Estrogens; D005290:Ferric Compounds; D005609:Free Radicals; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D004958:Estradiol; D016627:Oxidopamine; C024555:ferric chloride; D004298:Dopamine; D006719:Homovanillic Acid