Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor beta1 (TGF-beta1) in hippocampus: effect of a TGF-beta1 oligo-antisense.

Javier A Bravo; Claudio S Parra; Sandor Arancibia; Sergio Andrés; Paola Morales; Mario Herrera-Marschitz; Luisa Herrera; Hernán E Lara; Jenny L Fiedler

doi:10.1186/1471-2202-7-40

PubMed · 16712723

Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor beta1 (TGF-beta1) in hippocampus: effect of a TGF-beta1 oligo-antisense.

Javier A Bravo·Claudio S Parra·Sandor Arancibia·Sergio Andrés·Paola Morales·Mario Herrera-Marschitz·Luisa Herrera·Hernán E Lara·Jenny L Fiedler

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Abstract

BACKGROUND: Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor beta1 (TGF-beta1). Thus, we have investigated whether TGF-beta1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-beta1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats. RESULTS: It was observed an increase of apoptosis in DG, 2 and 5 days after ADX, in agreement with a reduction of corticosterone levels. However, the effect of ADX on the number of apoptotic positive cells in DG was decreased 5 days after the lesion. In CA1-CA3 regions, the effect was only observed 2 days after ADX. TGF-beta1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-beta1 ASO via an osmotic mini pump increased apoptosis levels in CA and DG regions 5 days after ADX as well as sham-operated control animals. No significant effect was observed following a scrambled-oligodeoxynucleotide treatment. CONCLUSION: The changes in both the pattern and the magnitude of apoptotic-cell morphology observed 2 and 5 days after ADX suggest that, as a consequence of the reduction of corticosteroids, some trophic mechanisms restricting cell death to a particular time window are elicited. Sustained intracerebral administration of TGF-beta1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-beta1 plays an anti-apoptotic role in vivo in hippocampus.

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Adrenalectomy Animals Apoptosis Cerebral Ventricles Corticosterone Gene Expression Hippocampus Male Oligodeoxyribonucleotides, Antisense RNA, Messenger Rats Rats, Sprague-Dawley Transforming Growth Factor beta Transforming Growth Factor beta1 Journal Article Research Support, Non-U.S. Gov't

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Javier A Bravo, Claudio S Parra, Sandor Arancibia, Sergio Andrés, Paola Morales, Mario Herrera-Marschitz, Luisa Herrera, Hernán E Lara, Jenny L Fiedler. 2006-05-19. Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor beta1 (TGF-beta1) in hippocampus: effect of a TGF-beta1 oligo-antisense.. https://doi.org/10.1186/1471-2202-7-40

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