Neurons in the hippocampus of chemobrain versus non-chemotherapy brain

doi:10.3969/j.issn.2095-4344.2017.28.016

Abstract

Abstract:

BACKGROUND: Chemotherapy drugs have been shown to penetrate the blood-brain barrier and cause neurotoxicity, further damaging nerve cells.
OBEJCTIVE: To investigate the changes in the expression and morphology of hippocampal neurons in chemobrain, and to investigate the underlying mechanism of nerve regeneration in chemobrain.
METHODS: The brain specimens were obtained from the six patients undergoing cancer chemotherapy and six patients without chemotherapy, and were then subdivided into two groups: < 60 years and > 60 years groups (n=3 per group). Immunofluorescence staining with specific antibodies was used to detect the changes in the morphology and number of neurons in the hippocampus CA1, CA2 and CA3.
RESULTS AND CONCLUSION: The number of neurons positive for NeuN, DCX and PV in the hippocampal CA1, CA2 and CA3 in the chemotherapy group was significantly lower than that in the non-chemotherapy group. Moreover, the neurons positive for PV were smaller, with less and shorter nervous processes. Immunofluorescence staining findings showed that the < 60 years old patients in the chemotherapy group had less neurons positive for NeuN and DCX than that in the non-chemotherapy; for > 60 years old patients, there was no significant difference between two groups. These findings suggest that chemotherapy can downregulate the expression of immature neurons in the hippocampus and reduce the number of neurons in the hippocampus. Moreover, chemotherapy can change the morphology and reduce the number of PV neurons.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Drug Therapy, Hippocampus, Neurons, Neoplasms, Tissue Engineering

CLC Number:

R318

Li Jian-ping, Lu Wei, Yang Lin, Xie Mi-xin, He Xu, Pan Ai-hua. Neurons in the hippocampus of chemobrain versus non-chemotherapy brain[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(28): 4523-4528.

Figures/Tables 2

2.1 两组标本脑海马锥体层NeuN+神经元数量海马NeuN+神经元主要分布于锥体层，而为分子层和多形层仅有少量分布；神经元胞体形态有圆形、椭圆形、锥体形和多边形；顶树突和底树突及其分支在锥体细胞的两极垂直于海马裂发出。化疗脑的NeuN+神经元排列松散，细胞密度明显下降，细胞出现少许空泡化的现象，细胞胞体模糊，突起变得杂乱，高龄组尤为明显。在< 60岁组中，化疗脑海马CA1、CA2、CA3区NeuN+细胞比未化疗脑少，差异有显著性意义(P < 0.001)(图1)。> 60岁组中，化疗脑海马CA1区NeuN+细胞比未化疗脑少，差异有显著性意义(P < 0.01)；化疗脑海马CA2区NeuN+细胞比未化疗脑少，差异有显著性意义(P < 0.05)；化疗脑海马CA3区NeuN+细胞比未化疗脑少，差异有显著性意义 (P < 0.05)(图2)。 2.2 两组标本化疗脑海马PV+神经元数量 PV+神经元稀疏分布于海马始层和锥体层，而多行层几乎没有分布。未化疗组PV+神经元胞体呈“圆形”或“吊灯”状，胞体和突起染色较深；突起多并相互交叉呈网状，突起长，伸入始层和锥体层甚至经锥体层伸入至多行层；化疗脑PV+细胞胞体较未化疗脑小，突起长度缩短，突起数目减少。在< 60岁组中，化疗脑海马CA1、CA2区PV+细胞比未化疗脑少，差异有显著性意义(P < 0.001)；化疗脑海马CA3区PV+细胞比未化疗脑少(P < 0.01)(图3)。> 60岁组中，化疗脑海马CA1区PV+细胞比未化疗脑少，差异有显著性意义(P < 0.01)；化疗脑海马CA2区PV+细胞比未化疗脑少，差异有显著性意义(P < 0.05)；化疗脑海马CA3区PV+细胞比未化疗脑少，差异有显著性意义(P < 0.01)(图4)。 2.3 两组标本脑海马DCX+神经元数量 DCX+神经元主要分布在海马锥体层，而始层和多行层也有分布。DCX+细胞胞体呈梭形或锥体形，突起在胞体两极伸出。在< 60岁组中，化疗脑海马CA1、CA2、CA3区DCX+细胞比未化疗脑少，差异有显著性意义(P < 0.01)(图5)。> 60岁组中，化疗脑海马CA1、CA2、CA3区DCX+细胞比未化疗脑少，差异有显著性意义(P < 0.001)(图6)。 2.4 两组标本免疫荧光组织化学染色NeuN+/DCX+共表达情况免疫荧光组织化学染色结果中，红色荧光显示为NeuN+神经元，绿色荧光显示为DCX+神经元。NeuN+神经元和DCX+神经元共表达在海马锥体层，而始层和多行层未见共表达细胞。< 60岁药物化疗组NeuN+/DCX+神经元共表达数量显著较未化疗组低(P < 0.001)；> 60岁药物化疗组NeuN+/DCX+神经元共表达数量与未化疗组无明显差异 (P > 0.05)(图7)。"

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