Lauterborn J C, Poulsen F R, Stinis C T, Isackson P J, Gall C M
Department of Anatomy and Neurobiology, University of California, Irvine 92697-1275, USA.
Brain Res Mol Brain Res. 1998 Mar 30;55(1):81-91. doi: 10.1016/s0169-328x(97)00368-9.
Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon-specific in situ hybridization was used to determine if adrenalectomy has differential effects on basal and activity-induced BDNF transcript expression in hippocampus. Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight increases in exon III-containing mRNA with 7-10-day survival and in exon II-containing mRNA with 30-days survival. In the dentate gyrus granule cells, adrenalectomy markedly potentiated increases in exon I and II cRNA labeling, but not increases in exon III and IV cRNA labeling, elicited by one hippocampal afterdischarge. Similarly, for the granule cells and CA1 pyramidal cells, hilus lesion (HL)-induced recurrent limbic seizures elicited greater increases in exon I and II cRNA hybridization in adrenalectomized (ADX) as compared to adrenal-intact rats. In this paradigm, adrenalectomy modestly potentiated the increase in exon III-containing mRNA in CA1 but had no effect on exon IV-containing mRNA content. These results demonstrate that the negative effects of adrenal hormones on activity-induced BDNF expression are by far the greatest for transcripts containing exons I and II. Together with evidence for region-specific transcript expression, these results suggest that the effects of stress on adaptive changes in BDNF signalling will be greatest for neurons that predominantly express transcripts I and II.
活动诱导的脑源性神经营养因子（BDNF）表达受到循环肾上腺类固醇的负调节。大鼠BDNF基因产生四种主要转录本形式，每种形式都包含一个独特的5'外显子（I-IV）和一个共同的3'外显子（V），后者编码BDNF蛋白。采用外显子特异性原位杂交技术来确定肾上腺切除术对海马中基础和活动诱导的BDNF转录本表达是否有不同影响。单独肾上腺切除术对BDNF mRNA水平的影响较小，存活7-10天时含外显子III的mRNA略有增加，存活30天时含外显子II的mRNA略有增加。在齿状回颗粒细胞中，肾上腺切除术显著增强了一次海马后放电引起的外显子I和II cRNA标记的增加，但没有增强外显子III和IV cRNA标记的增加。同样，对于颗粒细胞和CA1锥体细胞，与肾上腺完整的大鼠相比，海马损伤（HL）诱导的边缘性癫痫发作在肾上腺切除（ADX）大鼠中引起外显子I和II cRNA杂交的增加更大。在这种模式下，肾上腺切除术适度增强了CA1中含外显子III的mRNA的增加，但对含外显子IV的mRNA含量没有影响。这些结果表明，肾上腺激素对活动诱导的BDNF表达的负面影响，对于包含外显子I和II的转录本来说是最大的。结合区域特异性转录本表达的证据，这些结果表明，应激对BDNF信号适应性变化的影响，对于主要表达转录本I和II的神经元来说将是最大的。
