Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

Abstract

Context Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (neuron specific globin protein) attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by neuroglobin in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults. Objective To determine to what extent elevated neuroglobin ameliorates post smoke-inhalation brain bioenergetics and homeostasis in neuroglobin overexpressing transgenic mouse. Methods Smoke inhalation induced changes in bioenergetics were measured in the wild type and neuroglobin transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery. Results Cortical mitochondria from neuroglobin transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in neuroglobin transgene compared to wild type brain after smoke. Conclusion Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the neuroglobin overexpressing mouse, suggesting that neuroglobin mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury.

The Neuroprotective Effect of Hemin and the Related Mechanism in Sevoflurane Exposed Neonatal Rats

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Higher Reliance on Glycolysis Limits Glycolytic Responsiveness in Degenerating Glaucomatous Optic Nerve

“…This investigation is the first to analyze mitochondrial function in axons using the Seahorse XFe24 Analyzer. Though not designed for tissue, the Seahorse XFe Analyzer has been used to measure oxygen consumption rate in sections or explants of rat and mouse brain [11, 12] and mouse retina [13]; however, no one has yet utilized it to investigate glaucomatous ON. Therefore, we decided to use this method to analyze individual glaucomatous ONs and answer a fundamental question: Whether and how mitochondrial respiration is altered with glaucoma progression.…”

Acute inhalation of combustion smoke triggers neuroinflammation and persistent anxiety-like behavior in the mouse

“…All procedures were conducted in accordance with mandated standards of humane care and were approved by the UTMB Animal Care and Use Committee. We have previously developed a survival model of acute inhalation of wood smoke for the un-anesthetized rodent (Lee et al 2005; Chen L et al 2007; Lee et al 2009; Lee et al 2010; Lee et al 2011; Gorgun FM et al 2014). Briefly, smoke was generated by smoldering aspen wood shavings (1.3 gram/min) and dispersed by a tube-mounted fan into connected 20-liter transparent mouse exposure chamber.…”