1H-MRS characterization of metabolic changes induced by photoperiod in the sheep brain: a promising eye into in-vivo adult neurogenesis?

The hypothalamus is a central structure of the mammalian brain, which controls physiological, endocrine and metabolic brain homeostasis. Despite this essential role, little is known about the normal and altered neurochemical changes occurring within the hypothalamic structures. Here, the metabolism of the hypothalamus of ewes was investigated at 3T using proton magnetic resonance spectroscopy (1H-MRS). We used the sensitivity of these animals to photoperiod i.e. the ratio of day to night length, to investigate the hypothalamic metabolic changes and their relationship to hypothalamic adult neurogenesis. A longitudinal study involving 4 ewes per timepoint was conducted at 4 time points (P01, P02, P03 and P04) during long days (LD) and 4 time points during short days (SD). Significant metabolic changes were found between LD and SD at all time points in particular for glutamate (Glu), glutamine, myo-inositol and total N-acetyl-Aspartate (NAA). During SD, glutamate and glutamine concentrations were significantly smaller at P01 compared to all other time points while significant neurochemical changes occurred during the entire LD period. Neurochemical changes relative to P01 remained stable during LD and SD except for Glu and Gln which increased between P01 and P02 during SD. Relative metabolic changes were significantly higher on average for NAA and Glu and significantly smaller on average for total choline during SD compared to LD, respectively, paralleling the average changes in the numbers of neural stem cells and glial and oligodendrocyte progenitors found by immunohistochemistry. Despite important differences between MRS and immunohistochemistry in terms of spatial resolution, both techniques suggest complementary findings that should contribute to a better characterization of the hypothalamus during photoperiodism and adult neurogenesis. We conclude that 1H-MRS could be a promising non-invasive translational technique to investigate the existence of adult neurogenesis in-vivo in gyrencephalic brains.