Hypometabolism and neuronal network hyperactivity are early symptoms of Alzheimer’s disease. In fact, hippocampal neuronal hyperactivity has been linked to cognitive dysfunction in amnesic mild cognitive impairment. In this study, Zilberter and colleagues show that administration of dietary energy supplements (glucose, pyruvate and 3-beta-hydroxybutyrate) to mice, corrected detrimental changes induced by amyloid-beta(1-42).
Both normal and APPswe/PS1dE9 transgenic mice (model of Alzheimer’s disease) were studied in this report. In ex-vivo slices from transgenic mice, the authors found neuronal sub-populations with significantly depolarized resting and GABA-mediated current reversal potentials, mirroring abnormalities observed under acute amyloid-beta(1-42) application. Ex-vivo cortex of transgenic mice fed with standard diet displayed signs of impaired energy metabolism, such as abnormal NAD(P)H signaling and strongly reduced tolerance to hypoglycemia. APPswe/PS1dE9 transgenic mice also possessed brain glycogen levels twofold lower than those of normal mice.
These neuronal and metabolic dysfunctions were corrected in transgenic mice fed energy supplements (glucose, pyruvate and 3-beta-hyrdoxybutyrate) in their diet. In vivo, the dietary supplementation dampened neuronal hyperexcitability. The authors suggest that early Alzheimer-related neuronal dysfunction underlying hyperexcitability and energy metabolism deficiency may be prevented by dietary supplementation with specific energy substrates.
Zilberter M, Ivanov A, Ziyatdinova S, Mukhtarov M, Malkov A, Alpár A, Tortoriello G, Botting CH, Fülöp L, Osypov AA, Pitkänen A, Tanila H, Harkany T, Zilberter Y: Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer’s disease. J Neurochem. [Epub ahead of print, Dec. 14, 2012; doi: 10.1111/jnc.12127].