MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke

Abstract

Monocarboxylate transporter 2 (MCT2) is the predominant monocarboxylate transporter expressed by neurons. MCT2 plays an important role in brain energy metabolism. Stroke survivors are at high risk of cognitive impairment. We reported previously that stroke-induced cognitive impairment was related to impaired energy metabolism. In the present study, we report that cognitive function was impaired after stroke in rats. We found that MCT2 expression, but not that of MCT1 or MCT4, was markedly decreased in the rat hippocampus at 7 and 28 days after transient middle cerebral artery occlusion (tMCAO). Moreover, MCT2 overexpression promoted recovery of cognitive function after stroke. The molecular mechanism underlying these effects may be related to an increase in adenosine monophosphate-activated protein kinase-mediated mitochondrial biogenesis induced by overexpression of MCT2. Our findings suggest that MCT2 activation ameliorates cognitive impairment after stroke.

Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes

“…Four of these SNPs are upstream of GM23777 and 2 downstream; the remaining 250 SNPs are classified as intergenic. Based on previous research investigating the role of Slc16a7 in metabolism and cognitive performance ( Lev-Vachnish et al, 2019 ; Lu et al, 2015 ; Netzahualcoyotzi and Pellerin, 2020 ; Yu et al, 2021 ), we nominated this gene over identified gene modules. We next sought to determine if these SNPs were associated with enhanced or worsened late-life cognitive outcomes.…”

“…Genetic mapping using performance of CFM recall as a quantitative trait successfully identified Slc16a7 as a potential mediator of cognitive outcomes in individuals undergoing lifespan promoting CR and IF interventions. Slc16a7, which codes the lactate and pyruvate transporter protein MCT2 (Monocarboxylate transporter 2), has previously been implicated in age-related cognitive dysfunction in rodents and humans via neuronal lactate transport ( Lev-Vachnish et al, 2019 ; Lu et al, 2015 ; Netzahualcoyotzi and Pellerin, 2020 ; Yu et al, 2021 ). Lactate is an important energy source for de novo mRNA translation, a process critical for memory consolidation and recall ( Descalzi et al, 2019 ), and MCT2 functions in hippocampal neurons to achieve this demand for energy ( Netzahualcoyotzi and Pellerin, 2020 ).…”

Life-long Dietary Restrictions have Negligible or Damaging Effects on Late-life Cognitive Performance: A Key Role for Genetics in Outcomes

“…4 of these SNPs are upstream of GM23777 and 2 downstream, the remaining 250 SNPs are classified as intergenic. Based on previous research investigating the role of Slc16a7 in metabolism and cognitive performance (Lev-Vachnish et al, 2019; Lu et al, 2015; Netzahualcoyotzi and Pellerin, 2020; Yu et al, 2021), we prioritized this gene over identified gene modules. We next sought to determine if these SNPs were associated with enhanced or worsened late-life cognitive outcomes.…”

“…Mapping of late-life long-term memory performance successfully identified Slc16a7 as a potential mediator of cognitive outcomes in individuals undergoing lifespan promoting CR and IF interventions. Slc16a7 , which codes the lactate and pyruvate transporter protein MCT2 (Monocarboxylate transporter 2), has previously been implicated age-related cognitive disfunction in rodents and humans via neuronal lactate transportation (Lev-Vachnish et al, 2019; Lu et al, 2015; Netzahualcoyotzi and Pellerin, 2020; Yu et al, 2021). It is known that lactate is an important energy source for de novo mRNA translation, a process critical for long-term memory consolidation (Descalzi et al, 2019), and that MCT2 functions in hippocampal neurons to achieve this demand for energy (Netzahualcoyotzi and Pellerin, 2020).…”

Neuroprotective effects of tannic acid in the postischemic brain via direct chelation of Zn2+

“…Food and water were provided ad libitum . MCAO was performed as previously described (Yu et al 2021 ). Briefly, SD rats (250-300 g) were anesthetized with isoflurane (2% induction, 1.5% maintenance) using an oxygen/nitrous oxide (30/70%) mixture.…”