Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate

Int J Mol Sci. 2023 Nov 27;24(23):16818. doi: 10.3390/ijms242316818.

Abstract

Our previous studies showed that in patients with brain diseases, neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in the control of neuronal networks in an epileptic brain, we aimed to assess the GDNF levels in LF and BS as well as the BDNF and the hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (FE) and epilepsy and comorbid depression (FE + MDD) and to compare them with those of patients with major depressive disorder (MDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in FE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. GDNF concentrations in LF and BS positively correlated in HC, but not in patient groups. BDNF level was lower in BS of patients compared with HC and higher in FE + MDD taking valproates. A reduction in the GDNF level in LF might be an important biomarker of FE. Logistic regression models demonstrated that the probability of FE can be evaluated using GDNF in LF and BDNF in BS; that of MDD using GDNF in LF and cortisol and TNF-α in BS; and that of epilepsy with MDD using GDNF in LF and TNF-α and BDNF in BS.

Keywords: blood serum; brain-derived neurotrophic factor; cortisol; focal epilepsy; glial cell line-derived neurotrophic factor; hypothalamic–pituitary–adrenocortical axis; lacrimal fluid; major depressive disorder; tumor necrosis factor-α.

MeSH terms

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Depression
  • Depressive Disorder, Major* / complications
  • Epilepsies, Partial*
  • Epilepsy* / complications
  • Glial Cell Line-Derived Neurotrophic Factor
  • Humans
  • Tumor Necrosis Factor-alpha

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor
  • Tumor Necrosis Factor-alpha
  • GDNF protein, human