Metformin, a biguanide compound (N-1,1-dimethylbiguanide), is widely prescribed for diabetes mellitus type 2 (T2D) treatment. It also presents a plethora of properties, such as anti-oxidant, anti-inflammatory, anti-apoptosis, anti-tumorigenic, and anti-AGE formation activity. However, the precise mechanism of action of metformin in the central nervous system (CNS) needs to be clarified. Herein, we investigated the neuroprotective role of metformin in acute hippocampal slices exposed to methylglyoxal (MG), a highly reactive dicarbonyl compound and a key molecule in T2D developmental pathophysiology. Metformin protected acute hippocampal slices from MG-induced glutamatergic neurotoxicity and neuroinflammation by reducing IL-1β synthesis and secretion and RAGE protein expression. The drug also improved astrocyte function, particularly with regard to the glutamatergic system, increasing glutamate uptake. Moreover, we observed a direct effect of metformin on glutamate transporters, where the compound prevented glycation, by facilitating enzymatic phosphorylation close to Lys residues, suggesting a new neuroprotective role of metformin via PKC ζ in preventing dysfunction in glutamatergic system induced by MG.
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Foods
January 2025
Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
L. oligo-polysaccharides (CIOs), obtained from L., is a mixture of oligosaccharides and polysaccharides.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address:
Background: Fabry disease (FD) patients are known to be at high risk of developing neuropsychiatric symptoms such as anxiety, depression and cognitive deficits. Despite this, they are underdiagnosed and inadequately treated. It is unknown whether these symptoms arise from pathological glycosphingolipid deposits or from cerebrovascular abnormalities affecting neuronal functions in the central nervous system.
View Article and Find Full Text PDFTrimethyltin chloride (TMT), an organotin compound with potent neurotoxicity, is widely used as a heat stabilizer for plastics. However, the precise pathogenic mechanism of TMT remains incompletely elucidated, and there persists a dearth of sensitive detection methodologies for early diagnosis of TMT. In this study, Sprague-Dawley rats were treated with 10 mg/kg TMT to simulate acute exposure in humans.
View Article and Find Full Text PDFNeurotox Res
January 2025
Laboratory of Neurobiology of Aging, Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Fundación Ciencia & Vida, Avenida del Valle Norte 725, Huechuraba, Santiago, 8580702, Chile.
Mitochondria produces energy through oxidative phosphorylation (OXPHOS), maintaining calcium homeostasis, survival/death cell signaling mechanisms, and redox balance. These mitochondrial functions are especially critical for neurons. The hippocampus is crucial for memory formation in the brain, which is a process with high mitochondrial function demand.
View Article and Find Full Text PDFBMC Neurol
January 2025
Department of Neurology, School of Medicine, Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Introduction: Cerebral ischemic strokes cause brain damage, primarily through inflammatory factors. One of the regions most affected by middle cerebral artery occlusion (MCAO) is the hippocampus, specifically the CA1 area, which is highly susceptible to ischemia. Previous studies have demonstrated the anti-inflammatory properties of quercetin.
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