Metabolic Plasticity in Developing and Aging Brain

A. B. Salminaa, b, 1

a Research Center of Neurology, Moscow, Russia

b Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia

1Corresponding author; address: Volokolamskoe shosse 80, Moscow, 125367 Russia; e-mail: allasalmina@mail.ru. Abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; BBB, blood–brain barrier; DNA, deoxyribonucleic acid; IL, interleukin; NAD+(H), nicotinamide adenine dinucleotide (reduced); NVU, neurovascular unit; NSC, neural stem cell; NPC, neural progenitor cell; Aβ, amyloid-beta; APP, amyloid precursor protein; BACE-1, beta secretase; CAT, cationic amino acid transporter; CD, cluster differentiation; Cx, connexin; Fe65, adapter protein; GFAP, glial fibrillary acid protein; GLUT, glucose transporter; GPR81, G protein-coupled receptor 81; GSK3β, glycogen synthase kinase 3-beta; H2AX, H2A histone family member X; HIF-1, hypoxia-inducible factor-1; IRAP, insulin-regulated aminopeptidase; IRS1, insulin receptor substrate-1; MAPK, mitogen-activated protein kinase; MCT, monocarboxylate transporter; NLRP, inflammasome (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing); PKC, protein kinase C; RAGE, receptor for advanced glycation end-products; SIRT, sirtuin; VEGFR, vascular endothelial growth factor receptor.

Received 10 February, 2023

Abstract—Brain plasticity is a fundamental phenomenon based on various types of intercellular interactions (synaptic activity, neuritogenesis, synaptogenesis and elimination of synapses, and neuron-glia interactions), development, differentiation, migration of newly-born cells and cell death (neurogenesis/gliogenesis and neuronal or glial cell death, angiogenesis and regression of cerebral microvessels), and adaptation of tissue metabolism to changing environmental conditions. In this review, we discuss our own data and available literature in the context of regulation of certain types of energy metabolism (glycolysis and mitochondrial respiration) in neuronal, glial, and endothelial cells, the signaling functions of metabolites in nervous tissue, and the mechanisms of establishment of cerebral insulin resistance, pseudohypoxia, and associated neuroinflammation in brain pathology, as well as some prospects for detecting novel molecular markers of pathobiochemical processes associated with impaired metabolic plasticity in the developing and aging brain.

Keywords: brain, metabolism, energy production, brain development, brain aging, neurodegeneration, pseudohypoxia

DOI: 10.1134/S1819712423030157