Lactate-mediated neural plasticity genes emerged during the evolution of memory systems

Abstract

The ability to record experiences and learning is present to different degrees in several species; however, the complexity and diversity of memory processes are cognitive function features that differentiate humans from other species. Lactate has recently been discovered to act as a signaling molecule for neuronal plasticity linked to long-term memory. Because lactate is not only an energy substrate for neurons but also a signaling molecule for plasticity (Magistretti and Allaman in Nat Rev Neurosci 19:235–249, 2018. https://doi.org/10.1038/nrn.2018.19), it is of particular interest to understand how and when memory-related genes and lactate-mediated neural plasticity (LMNP) genes emerged and evolved in humans. To understand the evolutionary origin and processes of memory and LMNP genes, we first collected information on genes related to memory and LMNP from the literature and then conducted a comparative analysis of these genes. We found that the memory and LMNP genes have different origins, suggesting that these genes may have become established gradually in evolutionarily and functional terms and not at the same time. We also found that memory and LMNP systems have a similar evolutionary history, having been formed with the gradual participation of newly emerging genes throughout their evolution. We propose that the function of LMNP as a signaling process may be evolutionarily associated with memory systems through an unidentified system that is linked by 13 common genes between memory and LMNP gene sets. This study provides evolutionary insight into the possible relationship between memory and the LMNP systems that deepens our understanding of the evolution of memory systems.

Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner

“…Memory enhancement in old female neuronal Ldha KO mice could also be attributed to non-BDNF dependent mechanisms, such as increased LDHB-catalyzed lactate oxidization-dependent alterations in expression of immediate-early genes and synaptic plasticity genes. 109 , 177 There could be a shift with age toward neuronal LDHB dependent ANLS support within the hippocampus for cognitive processing. In fact, a recent finding saw global KO of Ldhb resulted in Y-maze spontaneous alternation and MWM learning and memory deficits along with apoptosis, neurodegeneration, and mitochondrial dysfunction typically associated with age-related cognitive decline.…”

Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases

“…Here, lactate acts as a signaling molecule, and NDMARs and downstream extracellular signal-regulated kinase (ERK1/2) signaling are activated in response to elevated calcium levels leading to increased expression of genes implicated in synaptic plasticity in neurons. Several genes involved in activity maintenance and neuronal plasticity have been identified, such as Arc, BDNF, c-Fos, and Zif268 [56,57,60] (Table 2). When using NMDAR antagonist MK801, the effect of lactate on the genes was abolished, therefore implying the activation of the genes is dependent on NDMAR activity [57,60].…”

“…Several genes involved in activity maintenance and neuronal plasticity have been identified, such as Arc, BDNF, c-Fos, and Zif268 [56,57,60] (Table 2). When using NMDAR antagonist MK801, the effect of lactate on the genes was abolished, therefore implying the activation of the genes is dependent on NDMAR activity [57,60].…”