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Journal of Integrative Neuroscience  2019, Vol. 18 Issue (2): 127-132    DOI: 10.31083/j.jin.2019.02.16
Original Research Previous articles | Next articles
Hippocampal neuron loss and astrogliosis in medial temporal lobe epileptic patients with mental disorders
Jun Lu1, *(), Hongxing Huang1, Qichang Zeng1, Xinmei Zhang2, Min Xu3, Yi Cai4, Qin Wang1, Yahui Huang1, Qiong Peng5, Lanqiuzi Deng1
1 Department of Neurosurgery, Hunan Provincial Brain Hospital, 410007, P. R. China
2 Department of Neurology, Central South University, 410000, P. R. China
3 Department of Pathology, Hunan Provincial Brain Hospital, 410007, P. R. China
4 Department of Psychiatry, Hunan Provincial Brain Hospital, 410007, P. R. China
5 Department of Neurology, Hunan Provincial Brain Hospital, 410007, P. R. China
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Abstract  

Hippocampal neuron loss and reactive astrogliosis are pathological features of medial temporal lobe epilepsy. Here, the expression of hippocampal astrogliosis-associated genes are studied in subjects with medial temporal lobe epilepsy and mental disorders (such as depression, anxiety and psychiatric comorbidities). The relationship between functional changes in hippocampus astrocytes and concurrent mental disorders are discussed. Nissl staining identified medial temporal lobe epilepsyinduced neuronal loss in the CA1 region of hippocampus. Quantitative real-time polymerase chain reaction and immunofluorescence technology were used to detect hippocampus glial fibrillary acidic protein, metallothionein, and aquaporin-4. The hippocampus area of subjects with medial temporal lobe epilepsy (with or without mental disorders) were smaller than the control group. Hippocampal neuronal loss and astrogliosis were more obvious in groups of medial temporal lobe epileptic patients with mental disorders. Relative protein levels of glial fibrillary acidic protein, metallothionein-I/II, and aquaporin-4 were significantly higher in subjects with medial temporal lobe epilepsy than seen in controls. Medial temporal lobe epileptic patients with mental disorder or depression had elevated metallothionein-I/II protein level when compared to controls and medial temporal lobe epileptic patients without mental disorder. Protein levels of glial fibrillary acidic protein and aquaporin-4 in medial temporal lobe epileptic patients with mental disorders were significantly lower than that in medial temporal lobe epileptic patients with no mental disorder. It is concluded that functional changes in hippocampus astrocytes are associated with mental disorders in medial temporal lobe epileptic patients and the astrogliosis-related genes of glial fibrillary acidic protein, metallothionein-I/II and aquaporin-4, are involved in this process.

Key words:  Medial temporal lobe epilepsy      mental disorder      astrocytes      glial fibrillary acidic protein      metallothionein-I/II      aquaporin-4     
Submitted:  19 January 2019      Accepted:  25 April 2019      Published:  30 June 2019     
*Corresponding Author(s):  Jun Lu     E-mail:  lujundsa@163.com

Cite this article: 

Jun Lu, Hongxing Huang, Qichang Zeng, Xinmei Zhang, Min Xu, Yi Cai, Qin Wang, Yahui Huang, Qiong Peng, Lanqiuzi Deng. Hippocampal neuron loss and astrogliosis in medial temporal lobe epileptic patients with mental disorders. Journal of Integrative Neuroscience, 2019, 18(2): 127-132.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2019.02.16     OR     https://jin.imrpress.com/EN/Y2019/V18/I2/127

Table 1  Clinical characteristics of MTLE patients.
Groups MTLE + W
N = 10
MTLE + P
N = 10
MTLE + D
N = 10
Gender
Male 7 (70) 4 (40) 6 (60)
Female 3 (30) 6 (60) 4 (40)
Family history of epilepsy
Yes 8 (80) 7 (70) 8 (80)
No 2 (20) 3 (30) 2 (20)
Age at epilepsy onset 45.7 ± 4.6 44.4 ± 7.2 46.4 ± 8.6
Disease duration (years) 15.6 ± 3.5 16.7 ± 1.2 18.5 ± 3.6
Monthly seizures (number) 4.1 ± 0.6 3.87 ± 0.02 4.02 ± 0.42
Figure 1.  Hippocampus neuron loss in subjects with MTLE. Nissl staining identifies MTLE-induced neuronal loss in the CA1 region of hippocampus. (A) Control; (B) MTLE without mental disorder (MTLE + W); (C) MTLE with mental disorder (MTLE + P); (D) MTLE with depression (MTLE + D). Representative photomicrographs of Nissl staining ( × 400) for each group.

Figure 2.  Relative hippocampal mRNA expression levels of GFAP, MT-I/II, and AQP4 elevated in patients with MTLE. Relative mRNA expression levels of (A) GFAP, (B) MT-I/II, and (C) AQP4, mean ± standard deviation (SD). *P < 0.05, **P < 0.01 compared with control; #P < 0.05, ##P < 0.01 compared with MTLE + W. F(3,8) = 21.568, F(3,8) = 51.175, and F(3,8) = 24.893, Fig. 2A-C, respectively.

Figure 3.  Elevated hippocampal GFAP, MT-I/II, and AQP4 level in subjects with MTLE. (A-C) Immunofluorescence of GFAP, MT-I/II, and AQP4 in hippocampal samples. (D-F) Integrated optic density (IOD) was analyzed for each section of A-C, mean ± standard deviation (SD). *P < 0.05, **P < 0.01 compared with control; #P < 0.05, ##P < 0.01 compared with MTLE + W. F(3,8) = 69.032, F(3,8) = 44.623, and F(3,8) = 50.745 for Fig. 3D-F, respectively.

Figure 4.  Elevated intracellular calcium signals of hippocampal astrocytes in MTLE subjects. Fluorescence calcium signals (F/F0) from control, MTLE without mental disorder (MTLE + W), MTLE with mental disorder (MTLE + P), and MTLE with depression (MTLE + D) are shown.Data presented as the mean ± standard deviation (SD). *P < 0.05, **P < 0.01 compared with control; #P < 0.05, ##P < 0.01 compared with MTLE + W F(3,8) = 44.108.

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