Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

Abstract

Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS) or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm.

Hypercapnia intensifies cerebral hypoxia via increasing cerebral oxygen extraction ratio: implication in neuroinflammation in hypoxemic adult rats

“…Hypoxemia, as a typical symptom of ARDS, decreases oxidative metabolism rate of the brain to avoid or reduce cerebral damage via preventing the PbtO 2 from dropping to a very low level [23]. In this study, we showed hypercapnia alone was not enough to increase or decrease the levels of PbtO 2 and CERO 2 .…”

“…Neurons and neuronal functions are highly sensitive to hypoxia. Under hypoxic conditions, the oxidative metabolism rate of the brain would decrease to prevent the partial pressure of brain tissue oxygen (PbtO 2 ) from dropping to a very low level [23,24]. However, it is still unknown whether hypercapnia would exert any effects on oxidative metabolism of the hypoxic brain.…”

MicroRNA-210 Knockout Alters Dendritic Density and Behavioural Flexibility

“…Previously, three separate studies have identified a significant downregulation of miR-210 in Alzheimer's disease (AD) patients at both late and early stages of AD as well as in sufferers of mild cognitive impairment (Cogswell et al, 2008;Hebert et al, 2008;Zhu et al, 2015). Both deficits in oxidative phosphorylation and increased oxidative stress in the brain are hallmarks of neurodegeneration and metabolic dysfunction is known to occur early in disease progression, preceding cognitive decline (Du et al, 2010;Watts et al, 2018a;Wirths et al, 2001). Identification of increased oxidative phosphorylation and ROS in miR-210 KO hippocampal neurons is therefore of interest and potentially significant to AD pathology.…”

Clinical and Biophysical Principles of Vascular Dementia and Alzheimer’s Disease Treatment

“…Понимание роли метаболизма и метаболически регулируемых генов в нейрональных функциях необходимо для выяснения роли как когнитивные функции нарушены в патологических условиях, при которых нарушается метаболизм нейронов. Установлены механизмы регулирование метаболизма нейронов, а также показана их роль во время гипоксии и окислительного стресса в норме и при нарушенной нейрональной функции [20].…”