| First Author | Pavlin T | Year | 2017 |
| Journal | Neurochem Res | Volume | 42 |
| Issue | 1 | Pages | 77-91 |
| PubMed ID | 28039592 | Mgi Jnum | J:323046 |
| Mgi Id | MGI:6880912 | Doi | 10.1007/s11064-016-2139-y |
| Citation | Pavlin T, et al. (2017) Loss or Mislocalization of Aquaporin-4 Affects Diffusion Properties and Intermediary Metabolism in Gray Matter of Mice. Neurochem Res 42(1):77-91 |
| abstractText | The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and alpha-syntrophin (alpha-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and alpha-syn KO. The second aim was to assess the effect of alpha-syn KO on cortical intermediary metabolism combining in vivo [1-(13)C]glucose and [1,2-(13)C]acetate injection with ex vivo (13)C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. alpha-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4-(13)C]glutamate and [4-(13)C]glutamine, and percent enrichment in [4-(13)C]glutamate were detected in the alpha-syn KO mice. [1,2-(13)C]acetate metabolism was unaffected in alpha-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, alpha-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites. |
