Granule cell mRNA levels for BDNF, NGF, and NT-3 correlate with neuron losses or supragranular mossy fiber sprouting in the chronically damaged and epileptic human hippocampus.
Granule cell mRNA levels for BDNF, NGF, and NT-3 correlate with neuron losses or supragranular mossy fiber sprouting in the chronically damaged and epileptic human hippocampus.
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DOI：
10.1007/bf02815150
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
G. Mathern;Thomas L. Babb;P. Micevych;Cesar E. Blanco;J. Pretorius
中科院分区：
文献类型：
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作者：
G. Mathern;Thomas L. Babb;P. Micevych;Cesar E. Blanco;J. Pretorius
本研究确定颞叶癫痫患者海马颗粒细胞神经营养因子mRNA表达、异常颗粒上苔藓纤维发芽和神经元丢失之间是否存在相关性。对9例手术切除的海马和3例尸检对照组织进行了以下研究：1.用原位杂交技术检测颗粒细胞脑源性神经营养因子（BDNF）、神经生长因子（NGF）和神经营养因子-3（NT-3）的mRNA水平;2.neo-Timm颗粒上苔藓纤维出芽; 3. Ammon角神经元密度。肿块病变和尸检;n=5）。结果显示，与非HS病例相比，HS患者的颗粒细胞BDNF、NGF和NT-3 mRNA水平升高（分别为p= 0.035，p = 0.04，p =0.045;单尾方向检验）。此外，颗粒细胞BDNF mRNA水平与阿蒙角神经元密度呈负相关（p=0.02），与更大的颗粒上苔藓纤维发芽呈正相关（p=0.02）。NGF mRNA水平与阿蒙角神经元密度呈负相关（p=0.02），TN-3 mRNA水平与手术年龄呈负相关（p=0.04），与更大的苔藓纤维发芽呈正相关（p=0.026）。这些结果表明，在慢性损伤的人类海马中，颗粒细胞表达神经营养素mRNA，并且mRNA水平与海马神经元损失或异常颗粒上苔藓纤维发芽相关。这些数据支持的假设，在癫痫人类海马，苔藓纤维突触可塑性，海马神经元损伤，颗粒细胞mRNA神经营养因子水平之间可能存在病理生理学关联。
This study determined in temporal lobe epilepsy patients if there were correlations among hippocampal granule cell expression of neurotrophin mRNAs, aberrant supragranular mossy fiber sprouting, and neuron losses. Consecutive surgically resected hippocampi (n=9) and comparison tissue from autopsies (n=3) were studied for:1.Granule cell mRNA levels usingin situhybridization for brainderived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3);2.neo-Timm supragranular mossy fiber sprouting; and3.Ammon’s horn neuron densities.Clinically, patients were classified into those with hippocampal sclerosis (HS;n=7) and non-HS cases (i.e., mass lesions and autopsies;n=5). Results showed that compared to non-HS cases, HS patients showed increased granule cell mRNA levels for BDNF, NGF, and NT-3 (p=0.035,p=0.04,p=0.045 respectively; one-tail directional test). Moreover, granule cell BDNF mRNA levels correlated inversely with Ammon’s horn neuron densities (p=0.02) and correlated positively with greater supragranular mossy fiber sprouting (p=0.02). NGF mRNA levels correlated inversely with Ammon’s horn neuron densities (p=0.02), and TN-3 mRNA levels correlated inversely with age at surgery (p=0.04) and correlated positively with greater mossy fiber sprouting (p=0.026). These results indicate in the chronically damaged human hippocampus that granule cells express neurotrophin mRNAs, and mRNA levels correlate with either hippocampal neuron losses or aberrant supragranular mossy fiber sprouting. These data support the hypothesis that in the epileptic human hippocampus, there may be pathophysiologic associations among mossy fiber synaptic plasticity, hippocampal neuron damage, and granule cell mRNA neurotrophin levels.