出生后大鼠前庭神经节中神经干细胞龛的证据：一项体外研究

文献信息

中文摘要

前庭功能障碍显著导致头晕、平衡问题和跌倒，但目前仍缺乏病因性治疗。前庭神经节（VG）是前庭神经的主要感觉神经节，日益被视为前庭变性的关键部位。神经干细胞（NSCs）已在听觉和前庭通路的多个区域中被发现。内源性激活NSCs代表一种有前景的再生策略。然而，VG内是否存在NSCs仍不确定。在本研究中，分离出生后第8天（PND 8）Sprague-Dawley大鼠的VG组织，经酶解消化，并在无血清神经球条件下培养。解离的VG细胞可靠地形成自由漂浮的神经球，并可在多次传代中生长。免疫细胞化学显示，神经球和VG组织切片中均表达NSC和祖细胞标志物，包括Sox-2、Nestin、Musashi-1、Atoh-1和双皮质素。进一步分析表明，成年VG中持续存在Sox-2、Atoh-1和Nestin阳性细胞群。分化后，来自神经球的单个细胞发育为β-III-微管蛋白阳性神经元、胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞和髓鞘碱性蛋白（MBP）阳性髓鞘形成胶质细胞，而相当一部分细胞保留Nestin表达，表明处于祖细胞样状态。这些发现表明，VG来源的细胞符合NSCs的主要标准：自我更新、祖细胞形成以及多能分化为神经元和胶质谱系。我们的结果首次提供了出生后大鼠VG中存在具有神经发生能力的细胞群的证据，并支持祖细胞相关细胞群持续至成年期。这将VG确定为一种新的内源性再生储备，使其成为激活驻留细胞以恢复前庭功能的策略的有前景靶点。

英文摘要

Vestibular dysfunction significantly contributes to dizziness, balance issues, and falls, yet causal treatments are still unavailable. The vestibular ganglion (VG), the primary sensory ganglion of the vestibular nerve, is increasingly seen as a key site of vestibular degeneration. Neural stem cells (NSCs) have been identified in several areas of the auditory and vestibular pathways. Endogenous activation of NSCs represents a promising regenerative strategy. However, the presence of NSCs within the VG remains uncertain. In this study, VG tissue from postnatal day (PND) 8 Sprague-Dawley rats was isolated, enzymatically dissociated, and cultured in serum-free neurosphere conditions. The dissociated VG cells reliably formed free-floating neurospheres that grew over multiple passages. Immunocytochemistry showed expression of NSC and progenitor markers, including Sox-2, Nestin, Musashi-1, Atoh-1, and doublecortin, in both neurospheres and VG tissue sections. Additional analyses demonstrated persistence of Sox-2-, Atoh-1-, and Nestin-positive populations in the adult VG. After differentiation, individual cells from neurospheres developed into β-III-tubulin-positive neurons, glial fibrillary acidic protein (GFAP)-positive astrocytes, and myelin basic protein (MBP)-positive myelinating glial cells, while a significant portion retained Nestin expression, indicating a progenitor-like state. These findings demonstrate that VG-derived cells meet the main criteria of NSCs: self-renewal, progenitor formation, and multipotent differentiation into neuronal and glial lineages. Our results provide the first evidence of a neurogenically capable cell population in the postnatal rat VG and support the persistence of progenitor-associated cell populations into adulthood. This identifies the VG as a novel endogenous regenerative reservoir, positioning it as a promising target for strategies that activate resident cells to restore vestibular function.