Altered expression of activating transcription factor 3 in the hippocampus of patients with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS)

Abstract

Aim of the study: Activating Transforming factor 3 (ATF3) is a stress induced gene and closely associated with neuro-inflammation while Transforming growth Factor Beta (TGFβ) signalling is also reported to be involved in neuro-inflammation and hyper-excitability associated with drug resistant epilepsy. Animal model studies indicate the involvement of ATF3 and TGFβ receptors to promote epileptogenesis. Human studies also show that TGFβ signalling is activated in MTLE-HS. However, lack of studies on ATF3 and TGFβRI expression in MTLE-HS patients exists. We hypothesize that ATF3 and TGFβRI might be expressed in hippocampi of patients with MTLE-HS and playing role in epileptogenesis. Materials & methods: Protein expression of ATF3 and TGFβRI was performed by western blotting. Localisation of ATF3 was performed by immunohistochemistry and immunoflorescence. Results: Protein expression of ATF3 and TGFβRI was significantly up-regulated in hippocampi of patients as compared to controls. Also ATF3 IR was significantly expressed in hippocampi of patients and ATF3 was expressed predominantly in cytoplasm as compared to nucleus. No correlation was found between ATF3 expression and epilepsy duration and seizure frequency. Conclusions: ATF3 and TGFβRI are both important players in neuro-inflammation and might potentiate epileptogenesis in these patients.

Keywords:

• MTLE patients
• neuro-inflammation
• ATF3
• TGFβRI
• epileptogenesis

Acknowledgement

We would like to acknowledge all the patients for participating in this study.

Disclosure statement

Disclosure of the authors stated no competing financial interests or personal relationships that could lead to any influence on the work reported in this article.

Author’s contribution

DP designed the research, performed research, analysed the data and wrote the article. A.S., J.B. and A.B.D. designed the research, analysed the data and wrote the article. M.T. designed the research and wrote the article. P.S. performed research. R.D. provided clinical samples. S.L. provided the autopsy samples. M.C.S & F.S. performed the histopathological examinations. P.S.C. provided clinical samples, designed the research and wrote the article. R.K.S. designed the research and wrote the article. All authors read and approved the final manuscript.

Data availability

The data is available on request to the corresponding author.

Additional information

Funding

We would like to acknowledge all the patients for participating in this study. This work was funded by Intramural grant (All-India Institute of Medical Sciences Intramural Research Fund, Project A622) of All India Institute of Medical Sciences, New Delhi and MEG resource facility grant by Department of Biotechnology, Ministry of Science and Technology, Govt. of India (BT/MED/122/SP24580/2018].