RT Journal Article
SR Electronic
T1 Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8604
OP 8609
DO 10.1523/JNEUROSCI.20-23-08604.2000
VO 20
IS 23
A1 Csaba Leranth
A1 Robert H. Roth
A1 John D. Elsworth
A1 Frederick Naftolin
A1 Tamas L. Horvath
A1 D. Eugene Redmond, Jr
YR 2000
UL http://www.jneurosci.org/content/20/23/8604.abstract
AB There are sexual differences in several parameters of the nigrostriatal dopamine neurons, as well as in the progression of diseases associated with this system, e.g., Parkinson's disease and dementia. These differences, as well as direct experimental data in rodents, suggest that gonadal hormones play a role in modulating this system. To determine whether circulating estrogen might have long-term effects by altering the number of dopamine neurons, the density of dopamine neurons was calculated in the compact zone of the substantia nigra of male and intact female short- (10 d) and longer-term (30 d) ovariectomized and short- and longer-term ovariectomized but estrogen-replaced nonhuman primates (African green monkeys). Furthermore, the number of tyrosine hydroxylase-expressing neurons, the total number of all types of neurons, and the volume of the compact zone of the substantia nigra were calculated in 30 d ovariectomized and in 30 d ovariectomized and estrogen-replaced monkeys. Unbiased stereological analyses demonstrated that a 30 d estrogen deprivation results in an apparently permanent loss of >30% of the total number of substantia nigra dopamine cells. Furthermore, the density calculations showed that brief estrogen replacement restores the density of tyrosine hydroxylase-immunoreactive cells after a 10 d, but not after a 30 d, ovariectomy. Moreover, the density of dopamine cells is higher in females than in males. These observations show the essential role of estrogen in maintaining the integrity of the nigral dopamine system, suggest a new treatment strategy for patients with Parkinson's disease and with certain forms of memory-impairing disorders, and provide another rationale for estrogen replacement therapy for postmenopausal women.