Genetic Dissection of BDNF and TrkB Expression in Glial Cells.

Genetic Dissection of BDNF and TrkB Expression in Glial Cells.
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DOI:
10.3390/biom14010091
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发表时间:
2024-01-11
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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脑源性神经营养因子(BDNF)及其高亲和力受体原肌球蛋白相关激酶受体B(Trk B)广泛表达于中枢神经系统。有充分的证据表明,神经元表达BDNF和全长TrkB(TrkB. FL)以及较低水平的截短TrkB(TrkB. T)。然而,关于BDNF和TrkB在神经胶质细胞,特别是小胶质细胞中的表达有相互矛盾的报道。在这项研究中,我们采用了一个敏感和可靠的遗传学方法来表征BDNF和TrkB在小鼠脑胶质细胞中的表达。我们利用了三种Cre小鼠品系,其中Cre重组酶在与BDNF、TrkB、FL或所有TrkB同种型相同的细胞中表达,并将它们与Cre依赖性报告小鼠杂交,用胞体定位的EGFP标记BDNF或TrkB表达细胞。我们用胶质细胞标记物进行免疫组织化学检测BDNF和TrkB在小胶质细胞、星形胶质细胞和少突胶质细胞中的表达。令人惊讶的是,我们没有发现BDNF或TrkB表达的小胶质细胞在检查的中枢神经系统区域,包括躯体运动皮质,海马CA1区,和脊髓。与先前的研究一致,大多数星形胶质细胞仅在成年大脑的海马中表达TrkB. T。此外,在海马中有少量表达BDNF的星形胶质细胞和少突胶质细胞,其功能有待确定。我们还发现,少突胶质细胞前体细胞,但不是成熟的少突胶质细胞,表达TrkB. FL和TrkB. T在成年小鼠海马。这些结果不仅阐明了BDNF和TrkB在神经胶质细胞中的表达,而且为研究BDNF和TrkB在星形胶质细胞和少突胶质细胞中的作用提供了机会。
The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL) as well as a lower level of truncated TrkB (TrkB.T). However, there are conflicting reports regarding the expression of BDNF and TrkB in glial cells, particularly microglia. In this study, we employed a sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent reporter mice to label BDNF- or TrkB-expressing cells with soma-localized EGFP. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB-expressing microglia in examined CNS regions, including the somatomotor cortex, hippocampal CA1, and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the hippocampus of adult brains. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF in the hippocampus, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the hippocampus of adult mice. These results not only clarify the expression of BDNF and TrkB in glial cells but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in astrocytes and oligodendrocytes.
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