Laboratory of Biology and Development of the Nervous System, School of Sciences, Pontifical Catholic University of Rio Grande do Sul, Ipiranga Av. 6681, 90619-900, Porto Alegre, Brazil; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 31.001, 9713 GZ, Groningen, the Netherlands.
Laboratory of Biology and Development of the Nervous System, School of Sciences, Pontifical Catholic University of Rio Grande do Sul, Ipiranga Av. 6681, 90619-900, Porto Alegre, Brazil.
Behav Brain Res. 2019 Oct 17;372:111965. doi: 10.1016/j.bbr.2019.111965. Epub 2019 May 21.
The role of mBDNF on the beneficial effects of cognitive stimulation on the brain remains controversial, as well as the potential of peripheral mBDNF as a biomarker of environmental effects on its central status. We investigated the effect of different environmental conditions on recognition memory, proBDNF, mBDNF and synaptophysin levels in the hippocampus, and on mBDNF levels in blood. Male Wistar rats (6 and 17 months-old) were assigned to cognitively enriched (EE), standard (SE) and impoverished (IE) environmental conditions for twelve weeks. Novel object recognition was performed at week 10. When the animals were 9 and 20-months old, hippocampus was collected for mBDNF, proBDNF and synaptophysin analysis; serum was analyzed for mBDNF levels. The cognitively EE improved recognition memory, resulted in a trend to increased hippocampal mBDNF and augmented synaptophysin levels. Accordingly, hippocampal mBDNF, proBDNF and synaptophysin were significantly higher in EE than IE animals. Hippocampal mBDNF was positively correlated to proBDNF, cellular and behavioral plasticity markers. No effect of age was seen on the studied variables. Moreover, no significant effects of EE or IE on serum mBDNF were observed. Serum mBDNF also failed to correlate with hippocampal mBDNF, proBDNF and with the cellular and behavioral plasticity markers. These findings indicate that mBDNF is involved in neuronal and behavioral plasticity mechanisms induced by cognitively enriched environments, and that peripheral mBDNF may not always be a reliable biomarker of the effects of environmental settings on central mBDNF and plasticity, which is of special interest from a translational research perspective.
mBDNF 在认知刺激对大脑的有益影响中的作用仍然存在争议，外周 mBDNF 作为环境对其中枢状态影响的生物标志物的潜力也是如此。我们研究了不同环境条件对识别记忆、proBDNF、mBDNF 和海马突触体素水平的影响，以及对血液中 mBDNF 水平的影响。雄性 Wistar 大鼠（6 个月和 17 个月大）被分配到认知丰富（EE）、标准（SE）和贫乏（IE）的环境条件下 12 周。在第 10 周进行新物体识别。当动物 9 个月和 20 个月大时，收集海马体用于 mBDNF、proBDNF 和突触体素分析；分析血清中的 mBDNF 水平。认知丰富的 EE 改善了识别记忆，导致海马 mBDNF 水平有升高的趋势，并增强了突触体素水平。因此，EE 组的海马 mBDNF、proBDNF 和突触体素水平明显高于 IE 组。海马 mBDNF 与 proBDNF、细胞和行为可塑性标志物呈正相关。研究变量与年龄之间没有明显的相关性。此外，EE 或 IE 对血清 mBDNF 没有显著影响。血清 mBDNF 也与海马 mBDNF、proBDNF 以及细胞和行为可塑性标志物没有相关性。这些发现表明，mBDNF 参与了认知丰富环境诱导的神经元和行为可塑性机制，外周 mBDNF 可能并不总是环境对中枢 mBDNF 和可塑性影响的可靠生物标志物，这从转化研究的角度来看特别有趣。
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