Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder

Brain Res Bull. 2024 Mar 15:110928. doi: 10.1016/j.brainresbull.2024.110928. Online ahead of print.ABSTRACTEpilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30mg/kg, 100mg/kg and 300mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100mg/kg significantly increased the discrimin...

Source: Brain Research Bulletin - March 17, 2024 Category: Neurology Authors: Kang-Ni Chen Qi-Lin Peng Dan-Feng Cao Zhao-Jun Wang Kai Zhang Xin-Yu Zhou Dong-Yu Min Bo-Ting Zhou Xiao-Yuan Mao Source Type: research