Bauer S, Hay M, Amilhon B, Jean A, Moyse E
Laboratoire de Physiologie Neurovégétative, UMR 6153 CNRS/UMR 1147 INRA/Université Paul Cézanne-Aix-Marseille-III, Faculté Saint-Jérome, Case Postale 352, Avenue Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France.
Neuroscience. 2005;130(1):75-90. doi: 10.1016/j.neuroscience.2004.08.047.
The dorsal vagal complex (DVC) encompasses the nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve (DMX) and the area postrema (AP), that altogether provide the major integrative center for the mammalian autonomic nervous system. The adult rat DVC has been reported to contain afferent-dependent concentration of the plasticity-promoting polysialylated form of neural cell adhesion molecule [J Neurosci 21 (2001) 4721; Eur J Neurosci 14 (2001) 1194]. This prompted us to assess the occurrence of neurogenesis in the DVC of adult rats. Cumulative in vivo labeling of cell proliferation with i.p. bromodeoxyuridine (BrdU) injections was combined with phenotypic markers and confocal microscopy on serial brainstem sections throughout the DVC extent. In basal condition, sparse BrdU+ nuclei were selectively detected in the DVC according to a discrete and reproducible pattern. Some of them were found to colocalize with the neuronal markers doublecortin, HuC/D, or neuronal-specific antigen (NeuN), demonstrating that neurogenesis does occur within the DVC of adult rat. In the NTS, 10% of the BrdU+ nuclei were also NeuN+. A comparable proportion of astrogliogenesis was found in the DVC. Nestin immunohistochemistry yielded a highly specific labeling pattern at the border between AP and NTS. These data may relate to the neural stem cells that have been reported in the floor of the IVth ventricle [J Neurosci 16 (1996) 7599]. In order to assess a possible modulation of neurogenesis by afferent input in vivo, unilateral vagotomy was performed prior to cumulative BrdU treatment. Such DVC deafferentation triggered a large increase of BrdU incorporation in the ipsilateral DVC, which was associated with microglial proliferation in the DMX and with increased genesis of neurons and astrocytes in the NTS. These findings establish DVC as a novel model of adult neurogenesis that is reactive to deafferentation.
背侧迷走神经复合体(DVC)包括孤束核(NTS)、迷走神经背运动核(DMX)和最后区(AP),它们共同构成了哺乳动物自主神经系统的主要整合中心。据报道,成年大鼠的DVC中含有依赖传入神经的可塑性促进多唾液酸化形式的神经细胞黏附分子[《神经科学杂志》21(2001)4721;《欧洲神经科学杂志》14(2001)1194]。这促使我们评估成年大鼠DVC中神经发生的情况。通过腹腔注射溴脱氧尿苷(BrdU)对细胞增殖进行累积体内标记,并结合表型标记和共聚焦显微镜对整个DVC范围内的脑干连续切片进行观察。在基础状态下,根据离散且可重复的模式,在DVC中选择性地检测到稀疏的BrdU+细胞核。其中一些被发现与神经元标记物双皮质素、HuC/D或神经元特异性抗原(NeuN)共定位,表明成年大鼠的DVC内确实发生了神经发生。在NTS中,10%的BrdU+细胞核也是NeuN+。在DVC中发现了相当比例的星形胶质细胞生成。巢蛋白免疫组织化学在AP和NTS之间的边界处产生了高度特异性的标记模式。这些数据可能与第四脑室底部报道的神经干细胞有关[《神经科学杂志》16(1996)7599]。为了评估体内传入神经输入对神经发生的可能调节作用,在累积BrdU处理之前进行了单侧迷走神经切断术。这种DVC去传入神经作用引发了同侧DVC中BrdU掺入的大量增加,这与DMX中的小胶质细胞增殖以及NTS中神经元和星形胶质细胞生成的增加有关。这些发现确立了DVC作为一种对去传入神经作用有反应的成年神经发生新模型。