The Early Decrease in N-Acetyl Aspartate / Glutathione, a Brain Health Marker, Induced by Vitamin A Deprivation in Rat is Reversed by Retinoic Acid†

ABSTRACT

Retinoids are involved in adult brain function and in neurodegenerative diseases. Decreased expression of synaptic plasticity markers and metabolic changes induced by 14 weeks of vitamin A deprivation (VAD₁₄) were previously evidenced in rat brain. We evaluate early metabolic changes (by HRMAS proton NMR spectroscopy) on biopsies of cortex, hippocampus and striatum (i) during VAD and (ii) after all trans Retinoic Acid administration.

In 10 wk VAD (VAD₁₀), metabolic changes appeared in the cortex: (i) N-acetyl aspartate (NAA, +15%, P=0.05 vs C₁₀), a neuronal density indicator, (ii) glutathione (GSH, +30%, P=0.05 vs C₁₀), an antioxidant status marker. Concerning the impact of VAD duration, the NAA/GSH ratio in cortex, hippocampus and striatum was unchanged in all controls, whereas it decreased in striatum and hippocampus of VAD₁₀ and in striatum and cortex of VAD₁₄. ATRA had an apparent regulatory action by increasing NAA/GSH ratio in hippocampus (VAD_{10+ATRA vs} VAD₁₀: +34%, P=0.03), the striatal ratio being rescued to control level. Gene expression of BACE and APP, which are amyloidogenesis markers, were unchanged in VAD₁₀ whereas VAD₁₄ seemed to activate cortical amyloidogenesis.

Hypoexpression of retinoid signaling during a short 10 wk period has consequences on brain metabolic profile and precedes the impaired expression of both amyloidogenesis and synaptic plasticity markers. Rat nutritional VAD represents a model of accelerated aging which mimics the course of aging. The NAA/GSH ratio reflects the balance between neuronal health and protection against reactive oxygen species, and could thus serve as a marker of brain health.

Keywords:

HRMAS, vitamin A deprivation, retinoic acid, brain metabolism, antioxidant status, neuronal health.