The astrocyte-neuron lactate shuttle (ANLS) model posits that astrocyte-generated lactate is transported to neurons to fuel memory processes. However, neurons express high levels of lactate dehydrogenase A (LDHA), the rate-limiting enzyme of lactate production, suggesting a cognitive role for neuronally generated lactate. It was hypothesized that lactate metabolism in neurons is critical for learning and memory. Here transgenic mice were generated to conditionally induce or knockout (KO) the\u00a0Ldha<\/i>\u00a0gene in CNS neurons of adult mice. High pattern separation memory was enhanced by neuronal\u00a0Ldha<\/i>\u00a0induction in young females, and by neuronal\u00a0Ldha<\/i>\u00a0KO in aged females. In older mice,\u00a0Ldha<\/i>\u00a0induction caused cognitive deficits whereas\u00a0Ldha<\/i>\u00a0KO caused cognitive improvements. Genotype-associated cognitive changes were often only observed in one sex or oppositely in males and females. Thus, neuronal-generated lactate has sex-specific cognitive effects, is largely indispensable at young age, and may be detrimental to learning and memory with aging.<\/p>\n","protected":false},"author":14,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[91],"class_list":["post-12020","ccna_publication","type-ccna_publication","status-publish","hentry","studies-relation-sexe-et-genre"],"acf":[],"yoast_head":"\n