Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1) in hippocampus: effect of a TGF-β1 oligo-antisense

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-β1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-β1 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.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-β1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-β1 plays an anti-apoptotic role in vivo in hippocampus.Recent studies have proposed that cytokines and growth factors may influence the outcome of the damage induced by neurodegenerative diseases [1,2]. Transforming growth factor β1 (TGF-β1) represents the prototype of a large family of growth factors that regulate cell growth, development, differentiation and cell death [3,4].TGF-βs have been detected at high concentrations in post-mortem brain from patients with Parkinson's [5] and Alzheimer's [6]diseases. Also, the presence of TGF-β1 promotes an accumulation of cellular mature amyliod protein precursor in a microglial cell line [7]. The expression of TGF-β1 is induced by hypoxia, ischemia and brain trauma in several brain regions, including the hippocampus [8-10]. However, whether the increased TGF-β1 expression observed in several neurological diseases has a beneficial or detrimental effect on neurons remains unclear.Examples for both pro-apoptotic