Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

Abstract

H MRS Brain Metabolism a b s t r a c tAlterations to brain homeostasis during development are reflected in the neurochemical profile determined noninvasively by 1 H magnetic resonance spectroscopy. We determined longitudinal biochemical modifications in the cortex, hippocampus, and striatum of C57BL/6 mice aged between 3 and 24 months . The regional neurochemical profile evolution indicated that aging induces general modifications of neurotransmission processes (reduced GABA and glutamate), primary energy metabolism (altered glucose, alanine, and lactate) and turnover of lipid membranes (modification of choline-containing compounds and phosphorylethanolamine), which are all probably involved in the frequently observed age-related cognitive decline. Interestingly, the neurochemical profile was different in male and female mice, particularly in the levels of taurine that may be under the control of estrogen receptors. These neurochemical profiles constitute the basal concentrations in cortex, hippocampus, and striatum of healthy aging male and female mice.

Longitudinal monitoring of metabolic alterations in cuprizone mouse model of multiple sclerosis using 1H-magnetic resonance spectroscopy

“…In line with other longitudinal MRS studies, a significant decrease of GSH (Duarte et al, 2014) and Glu (Boumezbeur et al, 2010;Duarte et al, 2014) was observed over time in the control group. The interpretation of alterations in Glc/tCr ratio observed in this study is complicated as isoflurane anesthesia can alter glucose homeostasis Kofke et al, 1987).…”

Conditional Human Immunodeficiency Virus Transactivator of Transcription Protein Expression Induces Depression-like Effects and Oxidative Stress

“…Since GSH is the principal endogenous antioxidant molecule (70), it might be expected that the higher GSH levels we detected reflect lower rather than higher oxidative stress levels. However, postmortem and in vivo imaging studies in healthy humans and animals indicate that brain GSH levels are relatively stable in mature mice until late adulthood/senescence, at which point GSH may increase or decrease in different brain regions (71,94–98). Thus, our observation of increased GSH levels in young adult (8–13 weeks old) Tat-expressing mice over the relatively short interval studied (8 days in MRS studies) likely indicates a pathophysiological state induced by Tat protein.…”

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

“…In contrast, glial oxidative metabolism was increased probably due to astrogliosis [44]. A large longitudinal MRS study in C57Bl/6 mice over 2 years further confirmed the ageinduced impairment in amino acid homeostasis, with substantial reduction in the levels of neuro-active amino acids including the major excitatory and inhibitory neurotransmitters, respectively glutamate and GABA [43]. These metabolic modifications that occur in the brain due to cellular damage accumulated during lifespan are crucial for functional deterioration in aged subjects [45] and are further accentuated in neurodegenerative disorders [42].…”

“…In turn, defects in energy metabolism at the level of the tricarboxylic acid (TCA) cycle, electron transport chain and oxidative phosphorylation further enhance the ROS production and affects amino acid homeostasis (see [43] and references therein). Moreover, faulty mitochondrial ATP synthesis triggers higher demand from glycolysis.…”

“…In addition, Penner et al found that glutamate concentration was increased in the Aging and Disease • Volume 6, Number 5, October 2015 307 right hippocampus of AD patients after four months of galantamine treatment relative to pre-treatment levels, and those variations in glutamate levels were related to variations in N-acetylaspartate (NAA) content and cognitive performance [57]. Interestingly, it has been recurrently demonstrated that the regional levels of NAA and glutamate in the brain are positively associated since both are mainly located within neuronal cells (see [43] and references there in). NAA is believed to be produced in neuronal mitochondria and then used for myelin synthesis in olygodendrocytes [58].…”