Department of Integrative Biosciences, Oregon Health and Science University School of Dentistry, Portland, OR 97239, USA.
Neuroscience. 2012 Apr 5;207:333-46. doi: 10.1016/j.neuroscience.2012.01.013. Epub 2012 Jan 18.
Cardiorespiratory control neurons in the brainstem nucleus tractus solitarius (NTS) undergo dramatic expansion of dendritic arbors during the early postnatal period, when functional remodeling takes place within the NTS circuitry. However, the underlying molecular mechanisms of morphological maturation of NTS neurons are largely unknown. Our previous studies point to the neurotrophin brain-derived neurotrophic factor (BDNF), which is abundantly expressed by NTS-projecting primary sensory neurons, as a candidate mediator of NTS dendritogenesis. In the current study, we used neonatal rat NTS neurons in vitro to examine the role of BDNF in the dendritic development of neurochemically identified subpopulations of NTS neurons. In the presence of abundant glia, BDNF promoted NTS dendritic outgrowth and complexity, with the magnitude of the BDNF effect dependent on neuronal phenotype. Surprisingly, BDNF switched from promoting to inhibiting NTS dendritogenesis upon glia depletion. Moreover, glia depletion alone led to a significant increase in NTS dendritic outgrowth. Consistent with this result, astrocyte-conditioned medium (ACM), which promoted hippocampal dendritogenesis, inhibited dendritic growth of NTS neurons. The latter effect was abolished by heat-inactivation of ACM, pointing to a diffusible astrocyte-derived negative regulator of NTS dendritic growth. Together, these data demonstrate a role for BDNF in the postnatal development of NTS neurons, and reveal novel effects of glia on this process. Moreover, previously documented dramatic increases in NTS glial proliferation in victims of sudden infant death syndrome (SIDS) underscore the importance of our findings and the need to better understand the role of glia and their interactions with BDNF during NTS circuit maturation. Furthermore, while it has previously been demonstrated that the specific effects of BDNF on dendritic growth are context-dependent, the role of glia in this process is unknown. Thus, our data carry important implications for mechanisms of dendritogenesis likely beyond the NTS.
脑干孤束核（NTS）中的心肺控制神经元在出生后的早期经历树突棘的显著扩张，此时 NTS 电路中的功能重塑发生。然而，NTS 神经元形态成熟的潜在分子机制在很大程度上仍是未知的。我们之前的研究表明，神经营养因子脑源性神经营养因子（BDNF），其由投射到 NTS 的初级感觉神经元大量表达，是 NTS 树突发生的候选介质。在本研究中，我们使用体外培养的新生大鼠 NTS 神经元，研究 BDNF 在 NTS 神经元神经化学鉴定的亚群的树突发育中的作用。在丰富的胶质细胞存在的情况下，BDNF 促进 NTS 树突的生长和复杂性，BDNF 作用的幅度取决于神经元表型。令人惊讶的是，在胶质细胞耗竭的情况下，BDNF 从促进 NTS 树突发生转变为抑制。此外，胶质细胞耗竭本身就会导致 NTS 树突生长显著增加。与这一结果一致的是，星形胶质细胞条件培养基（ACM）促进海马树突发生，却抑制 NTS 神经元的树突生长。后者的效应被 ACM 的热失活所消除，这表明 ACM 中有一个可扩散的星形胶质细胞源性的 NTS 树突生长的负调节因子。总的来说，这些数据表明 BDNF 在 NTS 神经元的出生后发育中起作用，并揭示了胶质细胞对这一过程的新影响。此外，先前在婴儿猝死综合征（SIDS）患者中记录到的 NTS 胶质细胞增殖的显著增加突显了我们研究结果的重要性，以及需要更好地理解胶质细胞及其与 BDNF 之间的相互作用在 NTS 回路成熟过程中的作用。此外，尽管之前已经证明 BDNF 对树突生长的特定影响取决于具体情况，但胶质细胞在这个过程中的作用是未知的。因此，我们的数据对 NTS 以外的树突发生机制具有重要意义。
