Aging, Sphingolipid Metabolism, and Vitamin K

As mentioned previously sphingolipids are integral to the brain’s physiology and vitamin K has been demonstrated to correlate with sphingolipids.

In a recent study with geriatric patients, vitamin K intake was observed and subsequent behavior profiles noted [7]. The geriatric participants which had low vitamin K intake scored significantly lower in the Mini Mental State Exam, a cognitive tool for assessing mental function, than those with medium to high vitamin K intake. In a different study, seniors with high serum concentrations of phylloquinone had higher test scores in their verbal episodic memory performances than those with low levels [8], suggesting that the relationship between vitamin K and cognition can affect information processing systems such as memory.

All of the major sphingolipids (sphingomyelin, gangliosides, cerebrosides, and sulfatides) have been demonstrated to change in both animals and humans as a result of aging [3]. Due to the interaction between sphingolipids, age, and the brain, as well as the correlation between vitamin K and sphingolipids, this is a potentially fruitful area for future research.

Sphingolipids are affected by aging. Aging changes sphingolipid metabolism which in turns affects brain physiology and, ultimately, behavior and cognition.

Manipulating Sphingolipids Causes Behavioral Alterations

In an interest to see whether manipulating ceramides, a particular type of sphingolipid, would have any effect on behavior, a group of researchers designed an experiment for that purpose. The experiment involved blocking an enzyme, neutral sphingomyelinase (nSMase2), crucial for ceramide synthesis, then they would measure the animals’ behavioral profiles. Their line of reasoning stems from the fact that the neurons of the dentate gyrus and the hippocampus are remarkably high in nSMase2 concentrations, implying that this enzyme is quite important for hippocampal-related memory formation [9].

So, the researchers set out to use inhibitor GW4869 via intraperitoneal injections, a method that is able to block nSMase2 activity in animal models. The control group received saline in their intraperitoneal injections. The administration began 7 days prior to testing and lasted for an additional two weeks, making a total of 21 injections.

After creating a control and an experimental group, the researchers measured the animals’ behavior, in order to determine whether manipulating nSMase2 would have any impact on behavior and cognition.

The researchers expected to see changes in memory and learning, given the fact that nSMase2 is abundant in brain regions known to be important for learning and memory.

To test spatial learning and memory abilities, a Morris Water Maze was used. The test was given 7 days after the GS4869 treatment began. Both experimental and control groups had equal swimming speed. However, when it came to learning the location of the platform through repeated trials, the experimental group did not show a decrease in latencies as the control group did. Furthermore, the analysis showed that the GS4869 mice spent less time in the target quadrant and in the area that surrounds the platform. The researchers interpreted these behavioral findings to mean that the mice with nSMase2 inhibited had a delay in forming spatial reference memories [9].

In the Radial Arm Water Maze, a maze with more spatial complexity than the Morris Water Maze that is used to measure episodic-like working memory, the control mice again outperformed those receiving the GW4869 inhibitor, indicating further impairments associated with the blocking of ceramide synthesis. In the Radial Arm Water Maze, the location of the platform changes on a daily basis, so each time the mice have to learn a new location. The GW4869 group had increased latencies in locating the platform in the subsequent trials and they also had fewer correct arm entries than the control group, indicating they were performing at chance level. Due to these additional behavioral findings, the researchers also concluded that nSMase2 inhibition (and thus the interference with ceramide synthesis) is also associate with issues in episodic-like working memory.