Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor Î²1 (TGF-Î²1) in hippocampus: Effect of a TGF-Î²1 oligo-antisense
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 Î²1 (TGF-Î²1). Thus, we have investigated whether TGF-Î²1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-Î²1 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-Î²1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-Î²1 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 bo th 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-Î²1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-Î²1 plays an anti-apoptotic role in vivo in hippocampus. Â© 2006 Bravo et al; licensee BioMed Central Ltd.
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|Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor ß1 (TGF-ß1) in hippocampus: Effect of a TGF-ß1 oligo-antisense
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