| First Author | Roy D | Year | 2022 |
| Journal | Neurochem Res | Volume | 47 |
| Issue | 6 | Pages | 1765-1777 |
| PubMed ID | 35347633 | Mgi Jnum | J:357718 |
| Mgi Id | MGI:7763912 | Doi | 10.1007/s11064-022-03568-2 |
| Citation | Roy D, et al. (2022) Enhanced Cortical Metabolic Activity in Females and Males of a Slow Progressing Mouse Model of Amyotrophic Lateral Sclerosis. Neurochem Res 47(6):1765-1777 |
| abstractText | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with selective degeneration of motor neurons in the central nervous system. The pathophysiology of ALS is not well understood. We have used (1)H-[(13)C]-NMR spectroscopy together with an administration of [1,6-(13)C(2)]glucose and [2-(13)C]acetate in female and male SOD1(G37R) mice to assess neuronal and astroglial metabolic activity, respectively, in the central nervous system in ALS condition. The female (p = 0.0008) and male (p < 0.0001) SOD1(G37R) mice exhibited decreased forelimb strength when compared with wild-type mice. There was a reduction in N-acetylaspartylglutamate level, and elevation in myo-inositol in the spinal cord of female and male SOD1(G37R) mice. The transgenic male mice exhibited increased acetate oxidation in the spinal cord (p = 0.05) and cerebral cortex (p = 0.03), while females showed an increase in the spinal cord (p = 0.02) only. As acetate is transported and preferentially metabolized in the astrocytes, the finding of increased rate of acetate oxidation in the transgenic mice is suggestive of astrocytic involvement in the pathogenesis of ALS. The rates of glucose oxidation in glutamatergic (p = 0.0004) and GABAergic neurons (p = 0.0052) were increased in the cerebral cortex of male SOD1(G37R) mice when compared with the controls. The female mice showed an increase in glutamatergic (p = 0.039) neurometabolic activity only. The neurometabolic activity was unperturbed in the spinal cord of either sex. These data suggest differential changes in neurometabolic activity across the central nervous system in SOD1(G37R) mice. |
