| First Author | Frame AK | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 7 | Pages | 110342 |
| PubMed ID | 39055955 | Mgi Jnum | J:350095 |
| Mgi Id | MGI:7662511 | Doi | 10.1016/j.isci.2024.110342 |
| Citation | Frame AK, et al. (2024) Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner. iScience 27(7):110342 |
| abstractText | The astrocyte neuron lactate shuttle 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 the Ldha gene in CNS neurons of adult mice. High pattern separation memory was enhanced by neuronal Ldha induction in young females, and by neuronal Ldha knockout in aged females. In older mice, Ldha Induction caused cognitive deficits whereas Ldha knockout 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. |
