Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, has significant health benefits. Previous studies reported decreased levels of DHA and DHA-containing phosphatidylcholines in the brain of animals suffering from Alzheimer’s disease, the most common type of dementia; furthermore, DHA supplementation has been found to improve brain DHA levels and memory efficiency in dementia. Oil extracted from the seeds of Plukenetia volubilis (green nut oil; GNO) is also expected to have DHA like effects as it contains approximately 50% α-linolenic acid, a precursor of DHA. Despite this, changes in the spatial distribution of DHA in the brain of animals with dementia following GNO or DHA supplementation remain unexplored. In this study, desorption electrospray ionization imaging mass spectrometry (DESI-IMS) was applied to observe the effects of GNO or DHA supplementation upon the distribution of DHA in the brain of male senescence-accelerated mouse-prone 8 (SAMP8) mice, a mouse model of dementia. DESI-IMS revealed that brain DHA distribution increased 1.85-fold and 3.67-fold in GNO-fed and DHA-fed SAMP8 mice, respectively, compared to corn oil-fed SAMP8 mice. Memory efficiency in SAMP8 mice was also improved by GNO or DHA supplementation. In summary, this study suggests the possibility of GNO or DHA supplementation for the prevention of dementia.

As an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like (TTLL) proteins, TTLL1 and TTLL7, which have been indicated to be important for neuronal polarity. In this study, we constructed pure lines of Ttll1 and Ttll7 knockout mice. Ttll knockout mice showed several abnormal behaviors. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analyses of these brains showed increases in glutamate, suggesting that tubulin polyglutamylation by these TTLLs acts as a pool of glutamate in neurons and modulates some other amino acids related to glutamate.