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| Status |
Public on Mar 08, 2018 |
| Title |
Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknow. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of FGFR1, Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons as a metabolic substrate contributing to fulfill their elevated energy requirements.
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| Overall design |
For both the mouse primary cortical neuron and cortical astrocyte cultures, control (1xPBS, N=4 per cell type) and Klotho-treated samples (1nM, N=4 per cell type) were incubated for 24 hours prior to RNA extraction.
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| Contributor(s) |
Mazucanti CH, Kawamoto E, Mattson MP, Scavone C, Camandola S |
| Citation(s) |
29493420 |
| Submission date |
Jun 14, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
|
| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA390550 |
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