The Effects Of Estrogen On Bcl-2 And Bax In Rat Brain

In order to research the mechanism of neuroprotective function of estrogen, the methold of immunohistochemical ultrasensitive SP was used to study the effects of estrogen on the expression of Bcl-2 and Bax in rat brain. The model of ovariectomized female Sprague-Dawley rat were established and then treated with 17β-estradiol to study the expression and distribution of Bcl-2 and Bax in the cerebellum, mesencephalon, diencephalon, and telencephalon, at last the mechanism of the effects were discussed. The main results as follows: 1. In the cerebellum, the immunoreactive products of Bcl-2 and Bax were distributed in cortex and nuclei cerebelli. In cortex, it were reserved mainly in stratum Purkinje cell and in the nuclei cerebelli, were reserved in nucleus golbosus, nucleus interpositus and nucleus fastigii. The positive products mainly located in cytoplasmic membrane, plasma and nuclear membrane in cortex, while in nuclei cerebelli, it also can be seen in the neurites. In ovariectomized group, the expression intensity and quantity of Bcl-2 were decreased, while the expression of Bax were increased, so the anti-apoptosis function of neurons were cut down. After 17β-estradiol treatment, Bcl-2 expressed stronger and Bax expression were reduced. It showed that estrogen can protect neurons of cerebellum by up-regulating Bcl-2 and/or down-regulating Bax. 2. Bcl-2 and Bax immunoreactive products were widely presented in mesencephalon, mainly in nucleus nervi oculomotorii, substantia nigra, nucleus rubber, nucleus nervi trochlearis, nucleus lemnisci lateralis, nucleus raphes, nucleus raphes dorsalis, nucleus tegmenti pedunculopontinus and nucleus pontine. The positive products were located mainly in cell membrane, plasma and nuclear membrane and some in neurites. When ovariectomized, the expression intensity and quantity of Bcl-2 were decreased while that of Bax were increased made the neurons sensitive to stimulation. After treated with 17?-estradoil, it were reversed. The results showed that estrogen can protect the mesencephalon neurons by up-regulating the expression of Bcl-2 and/or down-regulating Bax. 3. In the diencephalons, the immunoreactive products of Bcl-2 and Bax were expressed widely, mainly in corpus geniculatum lateralis, corpus geniculatum medialis, nucleus parafascicularis, nucleus parafascicularis inferior, nucleus dorsal hypothalami, nucleus ventral hypothalami, nucleus subthalamicus,nucleus habenula, nucleus lateral thalami, nucleus paraventricularis hypoythalami, nucleus arcuatus hypothalami, nucleus pre-opticus magno cellularis and nucleus supra-opticus. The immunoreactive products mainly existed in plasma, cytoplasmic membrane and nuclear membrane, also can be reserved in neurites. After ovariectomized, the expression of Bcl-2 were decreased while that of Bax were increased in corpus geniculatum lateralis, corpus geniculatum medialis and nucleus parafascicularis, ect. it made the neurons sensitive to stimulation. After treated with 17?-estradoil, the above results were reversed. It showed that estrogen protect the neurons in those area by up-regulating the expression of Bcl-2 and down-regulating Bax. In the nucleus dorsal hypothalami and nucleus paraventricularis hypoythalami, estrogen protect neurons mainly by up-regulating Bcl-2, while protect the neurons of nucleus lateral thalami by down-regulating Bax. 4. The positive products of Bcl-2 and Bax were widely distributed in telencephalon, mainly detected in cortex frontal, cortex cirguli, cortex piriformis, tuberculum olfactorium and nucleus septi, nucleus claustrum, amydgaloideus corticalis, hippocampus CA1,CA3, subiculum and dentate gyrus. The positive products were mainly presented in plasma and cytomembrane, some in nuclear membrane and neurites. In the mostly part of telencephalon, such as cortex frontal and nucleus septi, the intensity of Bcl-2 were significantly decreased, and the expression of Bax were increased in ovariectomized rat, which could be inhibited by treating with 17β-estradiol, even back to the normal level. It suggested that estrogen could up-regulate Bcl-2 while down-regulate Bax in the telencephalon of rat, and act the neuroprotective function. In cortex cirguli and CA1, estrogen act neuroprotective function mainly by up-regulating Bcl-2, while in cortex piriformis and tuberculum olfactorium decrease the sensitive of the neurons to stimulation by down-regulating Bax. The effects of estrogen on Bcl-2 and Bax in rat brain may play directly by classic pathway or indirectly by alternative pathway. In addition, we found it is interesting that the expression of Bax in nucleus rubber , nucleus pre-opticus magno cellularis, nucleus supra-opticus and cortex cirguli is significantly decreased after treated with 17β-estradiol when compared with sham group. It may because in those area exist some ERs or other regulator easier to integrate with 17β-estradiol exterior than estrogen interior. Whether there is other reason, it needs further study.