Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yihyang Kim Solomon Ergando Dube Chan Bae Park
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제1호, 1~8쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.01.01

국문 초록

The brain’s substantial metabolic requirements, consuming a substantial fraction of the body’s total energy despite its relatively small mass, necessitate sophisticated metabolic mechanisms for efficient energy distribution and utilization. The astrocyte-neuron lactate shuttle (ANLS) hypothesis has emerged as a fundamental framework explaining the metabolic cooperation between astrocytes and neurons, whereby astrocyte-derived lactate serves as a crucial energy substrate for neurons. This review synthesizes current understanding of brain energy metabolism, focusing on the dual roles of lactate as both an energy substrate and a signaling molecule. We examine the molecular underpinnings of metabolic compartmentalization, particularly the differential expression of lactate dehydrogenase (LDH) isozymes between astrocytes and neurons, which facilitates directional lactate flux. Recent evidence has challenged aspects of the classical ANLS model, revealing greater metabolic flexibility in neurons than previously recognized, including substantial LDHA expression and direct glucose utilization capabilities. Our recent studies on LDHB-deficient neurons provide new insights into the compensatory mechanisms and limitations of neuronal lactate metabolism, suggesting a more nuanced understanding of the ANLS hypothesis. Furthermore, we discuss lactate’s emerging role as a signaling molecule in synaptic plasticity, memory formation, and neuroprotection, particularly in ischemic conditions where elevated lactate levels correlate with enhanced neuronal survival through prostaglandin E2-mediated vasodilation. This comprehensive review integrates classical perspectives with recent advances, providing an updated framework for understanding brain lactate metabolism and its therapeutic implications in neurological disorders.

목차

INTRODUCTION

MITOCHONDRIA: BRAIN’S ATP POWERHOUSE

ANLS HYPOTHESIS

METABOLIC COMPARTMENTALIZATION

CRITICAL EVALUATIONS OF THE ANLS HYPOTHESIS

DUAL ROLES OF LACTATE IN BRAIN FUNCTION: ENERGY METABOLISM AND SIGNAL TRANSDUCTION

CONCLUSIONS

REFERENCES

키워드

Brain Energy metabolism Lactic acid L-lactate dehydrogenase