During vigorous exercise lactic acid (lactate) levels increase in the blood and during fasting and extended exercise the levels of the ketone BHB (b-hydroxybutyrate) increase. In this episode I talk with Stanford University professor Jonathan Long about his recent discovery that lactate and BHB in the blood are bound to the amino acid phenylalanine and that they (Lac-Phe and BHB-Phe) have beneficial effects on metabolic and brain health. Lac-Phe levels increase markedly in response to exercise in mice, humans, and race horses. Peripheral administration of Lac-Phe in suppresses food intake and reverses diet-induced obesity and insulin resistance in mice. Genetic ablation of Lac-Phe biosynthesis causes hyperphagy and obesity even in exercising mice showing a critical role for Lac-Phe in the beneficial effects of exercise. BHB-Phe has similar effects on food intake and metabolic health. We talk about the potential benefits of Lac-Phe and BHB-Phe for brain health and resilience.

LINKS

The Long laboratory webpage: https://longlabstanford.org/

Lac-Phe articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC9767481/pdf/nihms-1852727.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC10635077/pdf/nihpp-2023.11.02.565321v1.pdf

BHB-Phe article: https://www.cell.com/action/showPdf?pii=S0092-8674%2824%2901214-5

White matter consists of bundles of long axons that convey information between neural circuits between different brain regions within and between brain hemispheres. These long axons are wrapped with many layers of lipid-rich membranes of oligodendrocytes (a type of glial cell) and it is this ‘insulation’ that enables rapid propagation of signals over long distances. The axons in white matter consume high amounts of energy and their energy demand increases during extended physical exercise. In this episode Professor Carlos Matute talks about his interesting journey to become a neuroscientist and his fascinating discoveries concerning the function and dysfunction of oligodendrocyte neurobiology. He and his team recently provided evidence that the lipids in myelin are consumed by neurons in marathon runners during the event and then are replenished during their recovery. We also talk about how oligodendrocytes and axons in white matter are damaged by traumatic brain injuries, stroke, multiple sclerosis, and neurodegenerative disorders.

LINKS

About Carlos Matute

https://www.achucarro.org/director/carlos-matute/

White matter and marathon running

https://pmc.ncbi.nlm.nih.gov/articles/PMC12021653/pdf/42255_2025_Article_1244.pdf

Review articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC10454078/pdf/ijms-24-12912.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC4493393/pdf/fnana-09-00092.pdf

Michael Kreutz is Head of the Neuroplasticity Research Group at the Leibniz Institute for Neurobiology in Magdeburg Germany. Using powerful high resolution microscopy and molecular biology tools his laboratory has shown that autophagy occurs within synapses. Synaptic autophagy is stimulated by neural network activity and is critical for their maintenance and for learning and memory. Moreover, evidence suggests that conventional autophagy and exocytic autophagy prevent the abnormal accumulation of pathogenic proteins (Tau, TDP43, etc.) in neurodegenerative disorders. Pharmacological and lifestyle interventions that bolster synaptic autophagy may promote brain health and disease resistance.

LINKS

Kreutz Laboratory: https://www.kreutzlab.com/

Review article on autophagy and synaptic plasticity

https://www.cell.com/action/showPdf?pii=S0896-6273%2825%2900045-5

Activity-dependent protein expulsion in dendrites

https://www.cell.com/action/showPdf?pii=S2211-1247%2823%2901009-4

Golgi satellites in dendrites, NCAM, and LTP

https://www.cell.com/action/showPdf?pii=S2211-1247%2823%2900703-9