Metabolic effects of light deprivation in the prefrontal cortex of rats with depression-like behavior: In vivo proton magnetic resonance spectroscopy at 7T

Abstract

Recent evidence suggests that the glutamate system plays an important role in the pathogenesis of major depressive disorder (MDD). The aim of this study was to investigate the effects of light deprivation (LD) in the prefrontal cortex (PFC) of animals with depression-like behavior, targeting the glutamate system, using in vivo proton magnetic resonance spectroscopy (1H MRS). Male Sprague-Dawley rats were housed in constant darkness for six weeks (n = 12; LD group), while controls (n = 8) were housed under normal light cycles. The animals were assessed with forced swim tests. Point-resolved spectroscopy was used to quantify metabolite levels in the PFC. To substantiate the validity of the use of in vivo1H MRS in this study, the spectra obtained in the in vivo1H MRS, parametrically matched spectral simulation, and in vitro experiments were analyzed. The results of the spectral analyses showed that the quantification of glutamate and glutamine was not significantly affected by spectral overlaps. Thus, these results suggested that in vivo1H MRS can be used to reliably investigate the glutamate system. The results of the forced swim test showed LD-induced behavioral despairs in the animals. The levels of glutamate, myo-inositol, phosphocreatine, and total creatine were found significantly (p < 0.010) increased in the PFC of the LD animals compared with the controls. These results suggested that the LD-induced metabolic changes were consistent with the previous findings in patients with MDD and that short-echo-time in vivo1H MRS can be used to effectively measure depression-induced alterations in glutamate systems.