We investigated the role of the Ca(v)2.3 (alpha1E) channel in ischemic neuronal injury using Ca(v)2.3 mutant mice. In focal ischemia model with a complete occlusion of the middle cerebral artery in vivo, infarct at 24 h was significantly larger in Ca(v)2.3 mutant mice compared with that in wild-type controls. In vitro Ca2+ imaging studies using hippocampal slices revealed that oxygen-glucose deprivation induced a [Ca2+]i increase in the hippocampal CA1 region more vigorously in Ca(v)2.3 mutant mice than in wild-type controls, and that tetrodotoxin or bicuculline application abolished the difference between the genotypes. These results suggest that the Ca(v)2.3 channel plays a protective role in ischemic neuronal injury by a mechanism in which GABAergic neuronal actions are involved.
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http://dx.doi.org/10.1097/00001756-200202110-00018 | DOI Listing |
Antioxid Redox Signal
January 2025
Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Hypoxia ischemia (HI) is a leading cause of cerebral palsy and long-term neurological sequelae in infants. Given that mitochondrial dysfunction in neurons contributes to HI brain damage, this study aimed to investigate the regulatory role of miR-9-5p in mitochondrial function following HI injury. Overexpression of miR-9-5p in HI mice or HO-exposed PC12 cells suppressed neuronal injury, associated with increased mitochondrial copy number, normalizing mitochondrial membrane potential, improved nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activation, and downregulation of Keap1.
View Article and Find Full Text PDFClin Sci (Lond)
January 2025
Zhengzhou University First Affiliated Hospital, Zhengzhou, China.
Neddylation is a process of attaching neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to substrates for the protein function modulation via enzymatic cascades involving NEDD8-activating enzyme (E1), NEDD8-conjugating enzyme (E2), and NEDD8 ligase (E3). Defective in cullin neddylation 1 (DCN1) serves as a co-E3 ligase, that can simultaneously bind E2 UBE2M and cullin proteins to stabilize the catalytic center of the Cullin-Ring E3 ligase (CRL) complex, thereby promoting cullin neddylation. Neddylation is reported to be activated in diverse human diseases, and inhibition of protein neddylation has been regarded as a promising anticancer therapy.
View Article and Find Full Text PDFCell Death Dis
January 2025
Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, School of Basic Medicine, Shanxi Medical University, Taiyuan, China.
Programmed necrosis/necroptosis greatly contributes to the pathogenesis of cardiac disorders including myocardial infarction, ischemia/reperfusion (I/R) injury and heart failure. However, the fundamental mechanism underlying myocardial necroptosis, especially the mitochondria-dependent death pathway, is poorly understood. Synaptotagmin-1 (Syt1), a Ca sensor, is originally identified in nervous system and mediates synchronous neurotransmitter release.
View Article and Find Full Text PDFBrain Res
January 2025
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India. Electronic address:
Neurodegenerative disorders are characterized by a progressive loss of neurons, causing substantial deficits in motor and cognitive functioning. Bilirubin is a yellow by-product of heme, existing in two primary isoforms namely unconjugated and conjugated, while initially produced unconjugated isomer is lipophilic and cytotoxic in nature. At physiological levels, bilirubin has an important role in brain function by acting as a powerful antioxidant, preventing brain tissues from oxidative damage by eliminating reactive oxygen species (ROS).
View Article and Find Full Text PDFBrain Res Bull
January 2025
Graduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan; Research Institute of Disaster Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan; Health and Disease Omics Center, Chiba University, Chiba, Japan. Electronic address:
Ischemic stroke (IS) is a pathological condition characterized by the cessation of blood flow due to factors such as thrombosis, inflicting severe damage to the cranial nervous system and resulting in numerous disabilities including memory impairments and hemiplegia. Despite the critical nature of this condition, therapeutic options remain limited, with a pressing challenge being the development of treatments aimed at restoring neurological function. In this study, we leveraged zebrafish, renowned for their exceptional regenerative capabilities, to analyze the pathology of IS and the subsequent recovery process.
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