The effect of choline availability from gestation to early development on brain and retina functions and phospholipid composition in a male mouse model.

OBJECTIVES: Although choline is essential for brain development and neural function, the effect of choline on retina function is not well understood. This study examined the effects of choline on neural tissues of brain and retina, and membrane phospholipid (PL) composition during fetal development. METHODS: Pregnant C57BL/6 mice were fed one of 4 choline modified diets: i) control (Cont, 2.5g/kg), ii) choline deficient (Def, 0g/kg), iii) supplemented with choline chloride (Cho, 10g/kg) and iv) supplemented with egg phosphatidylcholine (PC, 10g/kg). At postnatal day (PD) 21, pups were weaned onto their mothers' respective diets until PD 45. Spatial memory was measured using the Morris Water Maze; retina function by electroretinogram (ERG); and PL composition with nuclear magnetic resonance spectroscopy. RESULTS: Cho and PC supplementation enhanced cued learning and spatial memory abilities, respectively (p Def > PC > Cho, with no statistically significant alterations in cone-driven responses. There were no differences in the composition of major PLs in the brain and retina. In the brain, subclasses of ether PL, alkyl acyl- phosphatidylethanolamine (PEaa) and phosphatidylcholine (PCaa) were significantly greater among the PC supplemented group in comparison to the Def group. DISCUSSION: These results indicate that while choline supplementation during gestation to an early developmental period is beneficial for spatial memory, contributions to retina function are minor. Assessment with a larger sample size of retinas could warrant the essentiality of choline for retina development.

Sex-Specific Effects of Chronic Creatine Supplementation on Hippocampal-Mediated Spatial Cognition in the 3xTg Mouse Model of Alzheimer's Disease.

The creatine (Cr) energy system has been implicated in Alzheimer's disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity- and disease-related protein levels, and mitochondrial function in the 3xTg hippocampus. Here, 3xTg mice were fed a control or Cr-supplemented (3% Cr (w/w)) diet for 8-9 weeks and tested in the Morris water maze. Mitochondrial oxygen consumption (Seahorse) and protein levels (Western blots) were measured in the hippocampus in subsets of mice. Overall, 3xTg females exhibited impaired memory as compared to males. In females, Cr supplementation decreased escape latency and was associated with increased spatial search strategy use. In males, Cr supplementation decreased the use of spatial search strategies. Pilot data indicated mitochondrial enhancements with Cr supplementation in both sexes. In females, Cr supplementation increased CREB phosphorylation and levels of IκB (NF-κB suppressor), CaMKII, PSD-95, and high-molecular-weight amyloid ß (Aß) species, whereas Aß trimers were reduced. These data suggest a beneficial preventative effect of Cr supplementation in females and warrant caution against Cr supplementation in males in the AD-like brain.

Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB.

The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting. Dietary Cr decreased escape latency/time to locate the platform (P < 0.05) and increased the time spent in the target quadrant (P < 0.01) in the Morris water maze. This was accompanied by increased coupled respiration (P < 0.05) in isolated hippocampal mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in Cr-fed mice, whereas IκB was decreased. These data demonstrate that dietary supplementation with Cr can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis.