Triheptanoin, an odd-medium-chain triglyceride, impacts brain cognitive function in young and aged mice.

ABSTRACTThe brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases.Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting.Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults.Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.

Toxicity of silver nanoparticles on different tissues in adult Danio rerio.

Although silver nanoparticles (AgNP) are among the most studied nanomaterials by virtue of their broad application in many areas, little is known about their overall toxicity to aquatic organisms after their contamination of the water environment. This study aimed to analyze the effect of the exposure (96 h) to different AgNP concentrations on Danio rerio (zebrafish) tissues. AgNP were synthesized and characterized by transmission electron microscopy (TEM), showing spherical AgNP of 30.00 ± 16.80 nm size. The effects of different AgNP concentrations (1, 3, and 5 µg L-1) on brain, muscle, gill, and liver tissues of zebrafish were investigated. The results show a significant decrease in brain and muscle acetylcholinesterase (AChE) activity. Liver and gill catalase (CAT) activity also decreased significantly. At the highest exposure concentration, muscle AChE was more inhibited (37.3%) than brain AChE (26.4%) and gill CAT was more inhibited (67.4%) than liver CAT (51.2%). D. rerio also showed gill morphological changes such as fusion of secondary lamellae, curvature, dilated marginal channel, and epithelial lifting. This study indicates that gill CAT together with morphological studies are potential biomarkers for AgNP.

Keto analogues and amino acids supplementation induces a decrease of white blood cell counts and a reduction of muscle damage during intense exercise under thermoneutral conditions.

This study evaluated the acute effect of keto analogue and amino acid (AA-KAAA) supplementation on both white blood cell counts and the established biomarkers of muscle damage during exercise under thermoneutral conditions. Sixteen male cyclists received a ketogenic diet for two days and were divided into two equal groups: a group taking AA-KAAA (KA) or a control group (PL). The athletes performed a two hour cycling session followed by a maximum incremental test until voluntary exhaustion (VExh). Blood samples were obtained at rest and during exercise for further hematological and biochemical analyses. Exercise-induced ammonemia increased in the PL group at VExh (75%) but remained unchanged in the KA group. Both groups exhibited a significant increase in leukocyte and neutrophil counts of ∼85% (∼13 × 109 L-1), but the shape of the lymphocytes and the eosinophil counts suggest that AA-KAAA supplementation helps prevent lymphocytosis. AA-KAAA supplementation induced a decrease in creatine kinase and aspartate aminotransferase levels at VExh while showing a significant decrease in lactate dehydrogenase at 120 min. We found that AA-KAAA supplementation decreases both the lymphocyte count response in blood and the established biomarkers of muscle damage after intense exercise under a low heat stress environment.

Daily changes of cytochrome oxidase activity within the suprachiasmatic nucleus of the Syrian hamster.

Cytochrome oxidase (CO) activity was studied over a 24-h period in the Syrian hamster suprachiasmatic nucleus (SCN) (site of the biological clock), anterior hypothalamic area (AHA), and motor cortex. The SCN CO activity was highest at the middle of the day (Zeitgeber time (ZT) 05), decreased at the end of the light period (ZT 10) and continued at a low level during the night (ZT 13, 16, 21.5 and 24). AHA and motor cortex showed a similar profile of CO activity and no changes of CO activity were found in animals maintained under darkness (DD). We propose that photic input plays a role in the SCN neuronal activity that modulates metabolic activity on this area.

Differential effect of changes in blood glucose levels on the velocity of propagation of cortical spreading depression in normal and malnourished rats.

The effects of intravenous glucose (1 ml, 40% solution) and insulin (1.5-3.0 U/kg in 0.2-0.4 ml Ringer solution) on the velocity of propagation (VP) of cortical spreading depression (SD) were studied in 36 well-nourished (W) and 25 malnourished (M) adult (90 days old) Wistar rats of both sexes. Blood glucose levels, measured 40-70 min after glucose, were increased by 330% in the W group (N = 18) and by 202.9% in the M rats (N = 12), when compared to the pre-injection levels. Insulin decreased it by 43.5% and 61.2% in W and M rats, respectively (N = 13). In the W rats, SD VP decreased after glucose and increased after insulin. The effect of glucose could not be attributed to increases in blood osmolarity, since iv mannitol (1 ml, 20% solution, N = 5) failed to decrease SD VP. The mean +/- SEM VP before and after the treatments were as follows (in mm/min): W rats, glucose 3.31 +/- 0.16 and 3.11 +/- 0.13; insulin 3.50 +/- 0.12 and 3.81 +/- 0.11; mannitol 3.53 +/- 0.46 and 3.92 +/- 0.48. In the M rats, the above effects on SD were not seen (SD VP: glucose 3.89 +/- 0.20 and 4.13 +/- 0.24; insulin 3.51 +/- 0.19 and 3.63 +/- 0.17). The results suggest that changes in the production of brain energy influence SD propagation.

Diferential effect of changes in blood glucose levels on the velocity of propagation of cortical spreading depression in normal and malnourished rats

The effects of intravenous glucose (1ml,40% solution) and insulin (1.5-3U/Kg in 0.2-0.4 ml Ringer solution) on the velocity of propagation (VP) of cortical spreading depression (SD) were studied in 36 well-nourished (W) and 25 malnourished (M) adult (90 days old) Wistar rats of both sexes. Blood levels, measured 40-70 min after glucose, were increased by 330% in the W group (N = 18) and by 202.9% in the M rats (N=12), when compared to the pre-injection levels. Insulin decreased it by 43.5% and 61.2% in W and M rats, respectively (N=13). In the W rats, SD VP decreased after glucose and increased after insulin. The effect of glucose could not be attributed to increases in blood osmolarity, since iv mannitol (1 ml, 20% solution, N = 5) failed to decrease SD VP. The mean ñ SEM VP before and after the treatments were as follows (in mm/min): W rats, glucose 3.31 ñ 0.16 and 3.11 ñ 0.13; insulin 3.50 ñ 0.12 and 3.81 ñ 0.11; mannitol 3.53 ñ 0.46 and 3.92 ñ 0.48. In the M rats, the above effects on SD were not seen (SD VP: glucose 3.89 ñ 0.20 and 4.13 ñ 0.24; insulin 3.51 ñ 0.19 and 3.63 ñ 0.17). The results suggest that changes in the production of brain energy influence SD propagation