Long-term changes in phospholipids and free fatty acids and the possible subcellular origins for phospholipid degradation in kainic acid-damaged mouse hippocampus

• Published in: Brain research 2024-12, Vol.1845, p.149243, Article 149243
• Main Authors: Suo, Jia-Le, Li, Jing-Yi, Zhou, Cheng-Mei, Jin, Rui-Lin, Song, Jia-Hui, Wang, Yan-Ling, Huo, De-Sheng, Tan, Bai-Hong, Li, Yan-Chao
• Format: Article
• Language: English
• Subjects: Animals; Cell Membrane - drug effects; Cell Membrane - metabolism; Excitatory Amino Acid Agonists - toxicity; Fatty Acids, Nonesterified - metabolism; Free fatty acid; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Kainic Acid - toxicity; Male; Mice; Mice, Inbred C57BL; Neuronal death; Neurons - metabolism; Neurons - pathology; Phospholipid; Phospholipids - metabolism; Plasma membrane; Status epilepticus
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2024.149243

•The changes of phospholipids were detected by Luxol Fast Blue histological staining for the first time.•The changes of phospholipid and free fatty acid levels in hippocampal neurons.•Morphological changes of cell membrane of hippocampal neurons. Kainic acid (KA)-induced excitotoxicity induces acute degradation of phospholipids and release of free fatty acids (FFAs) in rodent hippocampus, but the long-term changes in phospholipids or the subcellular origins of liberated FFAs remain unclarified. Phospholipids and FFAs were determined in KA-damaged mouse hippocampus by enzyme-coupled biochemical assays. The evolution of membrane injuries in the hippocampus was examined by a series of morphological techniques. The levels of phospholipids in the hippocampus decreased shortly after KA injection but recovered close to the control levels at 24 h. The decline in phospholipids was accelerated again from 72 to 120 after KA treatment. The levels of FFAs were negatively related to those of phospholipids, exhibiting a similar but opposite trend of changes. KA treatment caused progressively severe damage to vulnerable neurons, which was accompanied by increased permeability in the cell membrane and increased staining of membrane-bound dyes in the cytoplasm. Double fluorescence staining showed that the latter was partially overlapped with abnormally increased endocytic and autophagic components in damaged neurons. Our results revealed intricate and biphasic changes in phospholipid and FFA levels in KA-damaged hippocampus. Disrupted endomembrane system may be one of the major origins for KA-induced FFA release.