Hyperpalatable Diet and Physical Exercise Modulate the Expression of the Glial Monocarboxylate Transporters MCT1 and 4

Abstract

Hyperpalatable diets (HP) impair brain metabolism, and regular physical exercise has an apparent opposite effect. Here, we combined a prior long-term exposure to HP diet followed by physical exercise and evaluated the impact on some neuroenergetic components and on cognitive performance. We assessed the extracellular lactate concentration, expression of monocarboxylate transporters (MCTs), pyruvate dehydrogenase (PDH), and mitochondrial function in the hippocampus. Male C57BL/6J mice were fed 4 months with HP or a control diet. Subsequently, they were divided in the following groups: control diet sedentary (CDS), control diet exercise (CDE), HP diet sedentary (HPS), and HP diet exercise (HPE) (n = 15 per group) and were engaged for an additional 30-day period of voluntary exercise and HP diet. Relative to the control situation, exercise increased MCT1, MCT4, and PDH protein levels, while the HP diet increased MCT1 and MCT4 protein levels. The production of hydrogen peroxide (HO) and the mitochondrial membrane potential (∆Ѱ) stimulated by succinate in hippocampal homogenates were not significantly different between groups. ADP phosphorylation and the maximal respiratory rate induced by FCCP showed similar responses between groups, implying a normal mitochondrial function. Also, extracellular brain lactate levels were increased in the HPE group compared to other groups soon after performing the Y-maze task. However, such enhanced lactate levels were not associated with improved memory performance. In summary, hippocampal protein expression levels of MCT1 and 4 were increased by physical exercise and HP diet, whereas PDH was only increased by exercise. These observations indicate that a hippocampal metabolic reprogramming takes place in response to these environmental factors.

Metabolomic Analysis Identifies Lactate as an Important Pathogenic Factor in Diabetes-associated Cognitive Decline Rats

“…In the brain, MCT4 is expressed on astrocytes that are glycolytic and can supply other cells with lactate, while MCT1 is mainly detected in endothelial cells of the brain's blood vessels and in oligodendrocytes (39). MCT2 is found in the cell bodies, dendrites, and axons of neurons (39,40). In our study, we performed RT-PCR to determine the mRNA levels of MCT1, MCT2, and MCT4 in the hippocampi of the different diabetic groups.…”

Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration

“…The FCF for the CII-linked substrate stimulating STATE III respiration (succinate effect) was calculated as 1 -CI/CI&II, determined in the OxPHOS state in the protocol. [26][27][28][29] This analysis informs the influence of Complex II on the respirometry of other oxidative complexes. Since RCR ranges from 1.0 to infinity, we calculated the oxidative phosphorylation coupling efficiency, which has boundaries from 0.0 to 1.0 and is directly related to classic RCR (State III/State IV).…”

“…Fluorescence was monitored at excitation (563 nm) and emission (587 nm) wavelengths with a Spectra Max M5 microplate reader (Molecular Devices). 28…”

“…Based on this approach, functional aspects of oxidative phosphorylation, such as substrate uptake and oxidation, F0F1-ATP synthase activity, ubiquinone and cytochrome C pool size, and specific electron transport complexes activities can be evaluated using the RCR (respiratory control ratio), which is a respiratory index of the degree of metabolic coupling between ETS and oxidative phosphorylation. [26][27][28][29] Recently, Hill and colleagues 50 showed that isolated mitochondria from the ipsilateral cortex 3 days after TBI, present a deficient metabolism, which was followed by a recovery at Day 5 after injury. The authors hypothesized that by 5 days post-injury, no dysfunctional mitochondria remain in the injured brain.…”

Knockdown of astrocytic monocarboxylate transporter 4 (MCT4) in the motor cortex leads to loss of dendritic spines and a deficit in motor learning

“…with a viral vector approach to knockdown MCT4, where it was also shown to play a distinct role in memory acquisition using the Morris water maze (Netzahualcoyotzi & Pellerin, 2020). In addition to the hippocampus, MCT4 has been shown to play an important role in modulating hypothalamus-related behaviors, including feeding behaviors (Portela et al, 2017). Similar to our findings in the M1 primary motor cortex, MCT4 has also been shown to play a role in neuroplasticity of other cortical brain regions, including the prefrontal cortex, where knockdown of MCT4 led to loss of a passive coping response following stress exposure (Yin et al, 2021).…”