Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic research without primary human clinical data
PubMed 39725609 · doi:10.4196/kjpp.24.388
What was done
This narrative review synthesized literature on the astrocyte-neuron lactate shuttle (ANLS) hypothesis and brain energy homeostasis. It evaluated metabolic compartmentalization, differential lactate dehydrogenase (LDH) isozyme expression (including findings from LDHB-deficient neuronal models), direct neuronal glucose utilization, and lactate's signaling actions in synaptic plasticity, memory formation, and ischemic neuroprotection.
What was found
The abstract reports no numerical data or effect estimates. It qualitatively outlines that neurons possess greater metabolic flexibility than classical ANLS models proposed, expressing substantial LDHA and directly utilizing glucose. Additionally, it highlights that elevated lactate correlates with enhanced neuronal survival during ischemia via prostaglandin E2-mediated vasodilation.
Why it matters
The paper integrates recent mechanistic evidence into an updated framework of brain energetics, refining the understanding of neuronal metabolic autonomy and non-energetic signaling pathways relevant to neurological disorders.
Limits
As a narrative review, it lacks a systematic search protocol and formal quality appraisal. The underlying data derive primarily from in vitro and animal models rather than direct human clinical trials.
Cited by
- supports Lactate serves as a backup energy substrate for neurons in the brain.