Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system.
Humans; Animals; Neurons/*metabolism; Substantia Nigra/*metabolism; Corpus Striatum/metabolism; Dopamine/*physiology; Estrogens/*metabolism; Neuroprotective Agents/*metabolism
In this mini-review are first presented data which highlight the capacity and characteristics for estrogen to act as a neuroprotectant of the nigrostriatal dopaminergic system. Estrogen administration significantly attenuates the degree of striatal dopamine depletion to neurotoxins (MPTP, 6-OHDA and methamphetamine) which target the nigrostriatal dopaminergic system. This neuroprotection appears maximal with the 17-beta isomer, but some neuroprotection may also be present with the 17-alpha isomer of estradiol. Treatment with the anti-estrogen, tamoxifen, abolished estrogen's neuroprotective effects upon MPTP or methamphetamine-induced neurotoxicity. Estrogen also preserves striatal dopamine concentrations in gonadectomized male mice treated with MPTP, but neither testosterone nor dihydrotestosterone offer any neuroprotection. A brief review indicating a variety of potential means by which estrogen can function as a neuroprotectant is indicated. Included within this survey are presented estrogen's action as an antioxidant along with its capacity to affect monoamine oxidase, dopamine receptors/release, membrane morphology/fluidity, thermoregulation, blood flow and nitric oxide. This discussion is followed by a more detailed description of estrogen's actions upon the dopamine transporter, which is hypothesized to serve as one of the major mechanism involved with nigrostriatal dopaminergic neuroprotection. Overall, estrogen appears to inhibit dopamine transporter function by decreasing the affinity of the transporter. Such an effect could prevent neurotoxic agents from entering dopamine nerve terminals, thereby decreasing nigrostriatal neurodegeneration. Finally, some implications regarding this neuroprotectant capacity of estrogen are considered.
Dluzen D E
Journal of neurocytology
2000
2000-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Sex differences in dopamine- and vesicular monoamine-transporter functions.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Adrenergic Uptake Inhibitors/metabolism; Animal/drug effects; Animals; Behavior; Behavior/drug effects; Corpus Striatum/metabolism; Dopamine Agents/pharmacology; Dopamine Plasma Membrane Transport Proteins/*metabolism; Dopamine Uptake Inhibitors/metabolism; Female; Humans; Male; Methamphetamine/pharmacology; Mice; Nomifensine/metabolism; Reserpine/metabolism; Sex Factors; Vesicular Monoamine Transport Proteins/*metabolism
Men and women differ with regard to their use of, and responses to, methamphetamine (MA). Analogous sex differences with regard to MA are observed in animal models. In this report, data from a series of experiments that focus upon dopamine transporter (DAT) and vesicular monoamine transporter2 (VMAT2) function are reviewed by way of providing some understanding for these sex differences to MA. The amount of dopamine (DA) recovered after infusion of DA into superfused striatal tissue was greater in females and an accentuated amount of extracellular DA was obtained from females after infusion of the DAT-blocking drug, nomifensine. These data suggest a higher level of DAT activity in females. To evaluate the implications of this sex difference in DAT function as related to MA, the amount of DA evoked by an infusion of MA into superfused striatal tissue was tested and found to be significantly greater in males. In contrast, potassium chloride-stimulated DA release was greater in females. The results of these
Dluzen D E; McDermott J L
Annals of the New York Academy of Sciences
2008
2008-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1196/annals.1432.010" target="_blank" rel="noreferrer noopener">10.1196/annals.1432.010</a>