Depolarization of mitochondria in isolated CA1 neurons during hypoxia, glucose deprivation and glutamate excitotoxicity

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• 作者：Geir Arne Larsen ; Hå ; vard K. Skjellegrind ; Jon Berg-Johnsen ; Morten C. Moe and Morten Larsen Vinje
• 关键词：Mitochondria ; Mitochondrial membrane potential ; Hippocampus ; CA1 neuron ; Hypoxia ; Ischemia ; Rh 123
• 刊名：Brain Research
• 出版年：2006
• 出版时间：10 March 2006
• 年：2006
• 卷：1077
• 期：1
• 页码：153-160
• 全文大小：272 K

文摘

During cerebral ischemia neuronal injury is induced by a combination of hypoxia, hypoglycemia and glutamate excitotoxicity. To evaluate the relative importance of these factors on the mitochondrial function, acutely isolated rat hippocampal CA1 neurons were loaded with Rhodamine 123 to monitor the mitochondrial membrane potential (Δψ_m). During 15 min of hypoxia, a rapid and complete mitochondrial depolarization was observed in all neurons also when complex V of the respiratory chain was blocked by oligomycin. Glucose deprivation caused 77 % of the neurons to loose the Δψ_m completely, whereas most oligomycin-treated neurons retained their Δψ_m. During oxygen and glucose deprivation, a similar mitochondrial response was seen as in hypoxia. Although 15 min of high glutamate concentration (1 mM) provoked a rapid and irreversible increase in [Ca²⁺]_i, only 25 % of the neurons lost the Δψ_m. All oligomycin-treated neurons, however, lost the Δψ_m during glutamate exposure. In conclusion, the mitochondrial function of acutely isolated CA1 neurons is more sensitive to hypoxia than to glucose deprivation and glutamate excitotoxicity.