Hippocampal neuron loss and astrogliosis in medial temporal lobe epileptic patients with mental disorders.

J.j Lu ,Ya‐Hui Huang ,Qiong Peng,Qin Wang ,Xinmei Zhang,Yi Cai,Hongxing Huang,Qichang Zeng ,Min Xu,Lanqiuzi Deng

doi:10.31083/j.jin.2019.02.16

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 epilepsy-induced 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.

Highlights

Epilepsy is a common neurological disorder that affects approximately 4%–8% of the population in developed countries (Bell and Sander, 2001; Jallon, 2002)
3.2 Up-regulation of hippocampal Glial fibrillary acidic protein (GFAP), MT-I/II, and AQP4 level in subjects with medial temporal lobe epilepsy (MTLE) Relative expression levels of GFAP, MT-I/II, and AQP4 in hippocampus were analyzed from samples of MTLE subjects and controls using real-time polymerase chain reaction (RT-PCR)
The MTLE + P and MTLE + D groups had lower GFAP and AQP4 level compared with the MTLE + W group (#P < 0.05 and ##P < 0.01, respectively, Fig. 2A, C ), while the level of MT-I/II was much higher (#P < 0.05 compared with MTLE + W group, Fig. 2B)

Summary

Introduction

Epilepsy is a common neurological disorder that affects approximately 4%–8% of the population in developed countries (Bell and Sander, 2001; Jallon, 2002) It affects five million people in China and has profound impacts on the daily life of patients (Zhou et al, 2007). About 70% of patients could benefit from antiepileptic drug (AED) therapy, while another third of patients have poor seizure control (Zhou et al, 2007) This treatmentresistant epilepsy is called temporal lobe epilepsy (TLE), where medial temporal lobe epilepsy (MTLE) is the most common type (Engel, 1996). AQP4 is the predominant aquaporin found in the brain and is expressed in the cell membrane of astrocytes (Nagelhus et al, 2004). The alternative expression and regulation of AQP4 in epileptogenesis is not fully understood

Methods

Results

Conclusion