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Ten Days of Free Wheel Running Alters Cortical Glutamate‐Linked Mitochondrial Respiration in Rat Brain
Author(s) -
George Mitchell A. J.,
Brebner Karen,
Kane Daniel A.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1240.29
Subject(s) - endocrinology , medicine , hippocampus , dentate gyrus , respiration , chemistry , skeletal muscle , biology , anatomy
The mechanisms through which exercise benefits brain function are not completely understood. Appreciation for the role of lactate as a major neuroenergetic fuel, particularly during exercise, has progressed in recent decades; however, the mitochondrial involvement in brain lactate metabolism is not clear. To explore the mechanisms involved, we examined mitochondrial lactate oxidation in brain and skeletal muscle from exercised rats. Respiratory oxygen flux ( J O 2 ) was measured in saponin‐permeabilized prefrontal cortex (PFC) and hippocampus (dentate gyrus; DG) samples, as well as red and white gastrocnemius muscle samples from five male Wistar rats (age: approximately 104 days) given access to running wheels. Over ten days of free wheel running, rats attained a maximal daily running distance averaging 2.1 ± 0.5 km. The wheel‐running rats remained relatively weight stable, losing 1.4 ± 3.1 g body mass on average, whereas the five paired control rats gained an average of 39.4 ± 2.8 g over the ten days. On day eleven, high resolution respirometry was performed on exercise and control samples ex vivo . The addition of lactate failed to affect mitochondrial J O 2 (ADP + malate) from either brain or muscle in either group. However, J O 2 rose significantly following the addition of exogenous NAD + in each tissue ( P < 0.01), implying the lactate dehydrogenase reaction operates outside of the mitochondrial matrix. This interpretation was further supported by inhibition of J O 2 following addition of an inhibitor of pyruvate transport, UK‐5099 ( P < 0.01). Interestingly, the subsequent addition of glutamate resulted in a disparate increase in mitochondrial J O 2 among tissues and treatment. Compared to controls, glutamate‐supported mitochondrial J O 2 in wheel runners was significantly greater in PFC ( P < 0.05), but not DG. This rise in J O 2 likely reflects activation of the malate‐aspartate shuttle through elevated mitochondrial glutamate transport. Paradoxically, wheel runners exhibited lower glutamate‐supported J O 2 in red gastrocnemius ( P < 0.05). This may be due to the influence of regular exercise on the putative lactate‐malate‐aspartate shuttle. The lactate‐malate‐aspartate shuttle is the interaction between the lactate and malate‐aspartate shuttles to translocate reducing power to the mitochondria. The decline in lactate dehydrogenase activity in skeletal muscle that accompanies aerobic exercise training is expected to negatively influence lactate‐malate‐aspartate shuttling, and may explain our observations in muscle. Collectively, the results of this study suggest that electron shuttling in rat brain following ten days of voluntary exercise is upregulated in PFC. These results also provide further evidence for an indirect mechanism of mitochondrial lactate oxidation in both brain and skeletal muscle. Support or Funding Information The Natural Sciences and Engineering Research Council of Canada; The Nova Scotia Health Research Foundation