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Long-term administration of estrogen or tamoxifen to ovariectomized rats affords neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and Bax.
Brain Res. 2008 Apr 14; 1204:1-15.BR

Abstract

Recently we reported that chronic treatment with 17beta-estradiol (E2) or tamoxifen (TAM) regulates the ovariectomy-induced downregulation of the key molecules linked to hippocampal synaptic plasticity and signal transduction pathway. We now report modulation of the antiapoptotic (Bcl-2) and proapoptotic (Bax) proteins in the hippocampus of both the ovariectomized (OVX) rats as well as those given E2 or TAM subcutaneously as a daily dose for four weeks post-ovariectomy. Forty bilaterally OVX animals were divided into four groups of 10 each, namely i) OVX+E2 (0.1 mg/kg body weight), ii) OVX+TAM (0.05 mg/kg body weight), iii) OVX+vehicle (0.1 ml of sesame oil) and iv) OVX controls. An additional group of 10 animals constituted the ovary intact controls. Following culmination of treatment regimen, brain tissues of five animals from each group were processed for immunohistochemical staining of Bcl-2 and Bax on perfusion fixed cryo-sections. The remaining animals in each group were utilized for protein and Western blot analyses using unfixed hippocampal tissue. The results revealed that chronic administration of both E2 and TAM prevented the ovariectomy-induced downregulation of Bcl-2 and upregulation of Bax expression while restoring the Bcl-2/Bax ratio as observed in the ovary intact rats. Furthermore, TUNEL assay demonstrated a decline in the percentage of TUNEL positive cells in E2 or TAM treated groups. Confocal microscope studies of ERalpha and the apoptotic markers revealed that these two proteins co-reside in the same ERalpha positive hippocampal neurons. Thus, long-term E2 or TAM therapy modulates the apoptotic proteins and affords neuroprotection to the hippocampal neurons. Furthermore the estrogen-like effects of TAM point towards its potential as a beneficial therapeutic agent for neurodegenerative disorders, particularly in the postmenopausal women.

Authors+Show Affiliations

Department of Anatomy, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18342840

Citation

Sharma, K, and Raj D. Mehra. "Long-term Administration of Estrogen or Tamoxifen to Ovariectomized Rats Affords Neuroprotection to Hippocampal Neurons By Modulating the Expression of Bcl-2 and Bax." Brain Research, vol. 1204, 2008, pp. 1-15.
Sharma K, Mehra RD. Long-term administration of estrogen or tamoxifen to ovariectomized rats affords neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and Bax. Brain Res. 2008;1204:1-15.
Sharma, K., & Mehra, R. D. (2008). Long-term administration of estrogen or tamoxifen to ovariectomized rats affords neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and Bax. Brain Research, 1204, 1-15. https://doi.org/10.1016/j.brainres.2008.01.080
Sharma K, Mehra RD. Long-term Administration of Estrogen or Tamoxifen to Ovariectomized Rats Affords Neuroprotection to Hippocampal Neurons By Modulating the Expression of Bcl-2 and Bax. Brain Res. 2008 Apr 14;1204:1-15. PubMed PMID: 18342840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term administration of estrogen or tamoxifen to ovariectomized rats affords neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and Bax. AU - Sharma,K, AU - Mehra,Raj D, Y1 - 2008/02/12/ PY - 2007/05/08/received PY - 2008/01/17/revised PY - 2008/01/23/accepted PY - 2008/3/18/pubmed PY - 2008/7/23/medline PY - 2008/3/18/entrez SP - 1 EP - 15 JF - Brain research JO - Brain Res VL - 1204 N2 - Recently we reported that chronic treatment with 17beta-estradiol (E2) or tamoxifen (TAM) regulates the ovariectomy-induced downregulation of the key molecules linked to hippocampal synaptic plasticity and signal transduction pathway. We now report modulation of the antiapoptotic (Bcl-2) and proapoptotic (Bax) proteins in the hippocampus of both the ovariectomized (OVX) rats as well as those given E2 or TAM subcutaneously as a daily dose for four weeks post-ovariectomy. Forty bilaterally OVX animals were divided into four groups of 10 each, namely i) OVX+E2 (0.1 mg/kg body weight), ii) OVX+TAM (0.05 mg/kg body weight), iii) OVX+vehicle (0.1 ml of sesame oil) and iv) OVX controls. An additional group of 10 animals constituted the ovary intact controls. Following culmination of treatment regimen, brain tissues of five animals from each group were processed for immunohistochemical staining of Bcl-2 and Bax on perfusion fixed cryo-sections. The remaining animals in each group were utilized for protein and Western blot analyses using unfixed hippocampal tissue. The results revealed that chronic administration of both E2 and TAM prevented the ovariectomy-induced downregulation of Bcl-2 and upregulation of Bax expression while restoring the Bcl-2/Bax ratio as observed in the ovary intact rats. Furthermore, TUNEL assay demonstrated a decline in the percentage of TUNEL positive cells in E2 or TAM treated groups. Confocal microscope studies of ERalpha and the apoptotic markers revealed that these two proteins co-reside in the same ERalpha positive hippocampal neurons. Thus, long-term E2 or TAM therapy modulates the apoptotic proteins and affords neuroprotection to the hippocampal neurons. Furthermore the estrogen-like effects of TAM point towards its potential as a beneficial therapeutic agent for neurodegenerative disorders, particularly in the postmenopausal women. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/18342840/Long_term_administration_of_estrogen_or_tamoxifen_to_ovariectomized_rats_affords_neuroprotection_to_hippocampal_neurons_by_modulating_the_expression_of_Bcl_2_and_Bax_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(08)00225-4 DB - PRIME DP - Unbound Medicine ER -