Association of Mitochondrial Letm1 with Epileptic Seizures

Abstract

Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial protein that is associated with seizure attacks in Wolf-Hirschhorn syndrome. This study aimed to investigate the expression pattern of Letm1 in patients with temporal lobe epilepsy (TLE) and pilocarpine-induced rat model of epilepsy, and to determine if altered Letm1 leads to mitochondrial dysfunction and increased susceptibility to seizures. Using immunohistochemical, immunofluorescent, western blotting, and transmission electron microscopic methods, we have found that Letm1 was significantly decreased in TLE patients, and gradually decreased in experimental rats from 1 to 7 days after onset of seizures. Letm1 knock-down by a lentivirus bearing LV-Letm1-sh resulted in mitochondrial swelling and decreased expression of Letm1 target protein mitochondrially encoded cytochrome B (MT-CYB). Behavioral study revealed that inhibition of Letm1 caused early onset of the first seizure, increased seizure frequency, and duration. However, administration of Letm1 homolog nigericin failed to prevent epilepsy. These results indicate that inhibition of Letm1 and mitochondrial dysfunctions contributes to the development of epileptic seizures. Appropriate Letm1 level may be critical for maintaining normal neuronal functions.

Inhibition of Cgkii Suppresses Seizure Activity and Hippocampal Excitation by Regulating the Postsynaptic Delivery of Glua1

“…Sixteen epileptic and 10 control brain tissue samples were randomly selected from the epilepsy and control brain tissue banks established by our research team, respectively [19]. The samples in our epilepsy brain tissue bank were all obtained from drug-refractory epileptic patients.…”

“…The specimens in our control tissue bank originated from patients who underwent surgery to treat increased intracranial pressure caused by head trauma, and Table 2 summarizes the clinical characteristics of the 10 control patients. The brain tissue inclusion criteria and processing protocol are described in our previous publications [19, 20]. No significant difference in age or the female/male ratio was observed between the TLE group and the control group (P>0.05).…”

“…Western blot analysis was performed according to published protocols [19]. The total protein from homogenized rat and human brain tissues was extracted in RIPA lysis buffer (Beyotime Institute of Biotechnology, Jiangsu, China) following the manufacturer’s recommended protocols.…”

Integrated Quantum Therapy in an Epileptic Child after 13 Years of Inherited Real Risk of Epilepsy in Evolution: A Case Study

“…Mitochondrial genome analysis is rarely carried out in the investigation of various diseases, including epilepsy. In mesial temporal lobe epilepsy (MTLE) -hippocampal sclerosis (HS) -cases, mitochondrial genome analysis showed evidence of mitochondrial dysfunctions caused by important mutations associated with epilepsy (Zhao et al, 2008;Zhang et al, 2013). There are similar evidences in Early Infantile Epileptic Encephalopathy (Palmieri, 2008).…”

Elevated Expression of the Delta-Subunit of Epithelial Sodium Channel in Temporal Lobe Epilepsy Patients and Rat Model

“…The protocol was in compliance with the Declaration of Helsinki of the World Medical Association guidelines. Twenty-four surgically removed, temporal neocortex samples obtained from patients with intractable TLE and 12 histologically normal, temporal neocortex tissues obtained from patients undergoing surgical therapy for post-trauma intracranial hypertension were randomly chosen from our established brain tissue bank (Zhang et al 2014;Wang et al 2015). Diagnosis of each epilepsy patient was according to criteria established by the International League Against Epilepsy (Kwan et al 2010).…”