Lactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons
| Autor: | Cristina M. Alberini, Virginia Gao, Michael Q. Steinman, Giannina Descalzi, Akinobu Suzuki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Lactate transport
Male Monocarboxylic Acid Transporters Glycogenolysis Memory Episodic Citric Acid Cycle Medicine (miscellaneous) Inhibitory postsynaptic potential Hippocampus General Biochemistry Genetics and Molecular Biology Article Learning and memory 03 medical and health sciences 0302 clinical medicine Gangliosides Pyruvic Acid medicine Avoidance Learning Animals Rats Long-Evans Lactic Acid RNA Messenger lcsh:QH301-705.5 030304 developmental biology Memory Consolidation Neurons 0303 health sciences Gene knockdown Memory Disorders Arc (protein) Chemistry Brain Translation (biology) Cell biology Rats medicine.anatomical_structure nervous system lcsh:Biology (General) Astrocytes Excitatory postsynaptic potential General Agricultural and Biological Sciences Astrocyte 030217 neurology & neurosurgery Consolidation Neuroscience |
| Zdroj: | Communications Biology, Vol 2, Iss 1, Pp 1-11 (2019) Communications Biology |
| ISSN: | 2399-3642 |
| Popis: | Glycogenolysis and lactate transport from astrocytes to neurons is required for long-term memory formation, but the role of this lactate is poorly understood. Here we show that the Krebs cycle substrates pyruvate and ketone body B3HB can functionally replace lactate in rescuing memory impairment caused by inhibition of glycogenolysis or expression knockdown of glia monocarboxylate transporters (MCTs) 1 and 4 in the dorsal hippocampus of rats. In contrast, either metabolite is unable to rescue memory impairment produced by expression knockdown of MCT2, which is selectively expressed by neurons, indicating that a critical role of astrocytic lactate is to provide energy for neuronal responses required for long-term memory. These responses include learning-induced mRNA translation in both excitatory and inhibitory neurons, as well as expression of Arc/Arg3.1. Thus, astrocytic lactate acts as an energy substrate to fuel learning-induced de novo neuronal translation critical for long-term memory. Descalzi et al. show that pyruvate and ketone body B3HB rescue the memory deficits caused by the glia-specific knockdown of monocarboxylate transporters in the rat hippocampus. Astrocytic lactate is also required for learning-induced de novo protein synthesis in excitatory and inhibitory neurons, highlighting its importance in memory consolidation. |
| Databáze: | OpenAIRE |
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