A team of researchers has built a mathematical model that describes the molecular events associated with the beginning stage of learning and memory formation in the human brain.
The research, published in the journal Proceedings of the National Academy of Sciences, paves the way for understanding cognitive function and neurodegenerative diseases—at the molecular and cellular levels.
The study focuses on the dynamics of dendritic spines, which are thorny structures that allow neurons to communicate with each other. When a spine receives a signal from another neuron, it responds by rapidly expanding in volume—an event called transient spine expansion.
Transient spine expansion is one of the early events leading up to learning and memory formation. It consists of a cascade of molecular processes spanning four to five minutes, beginning when a neuron sends a signal to another neuron.
Many of the molecular processes leading up to transient spine expansion have already been identified experimentally and reported in the literature. Here, the authors built a map of many of these known processes into a computational framework.
“Spines are dynamic structures, changing in size, shape and number during development and aging. Spine dynamics have been implicated in memory, learning and various neurodegenerative and neurodevelopmental disorders, including Alzheimer’s, Parkinson’s and autism. Understanding how the different molecules can affect spine dynamics can eventually help us demystify some of these processes in the brain,” said Padmini Rangamani, a mechanical engineering professor at the University of California San Diego and first author of the study.
“This work shows that dendritic spines, which are sub-micrometer compartments within individual neurons, are the prime candidates for the initial tag of transient, millisecond synaptic activity that eventually orchestrates memory traces in the brain lasting tens of years,” said Shahid Khan, senior scientist at the Molecular Biology Consortium at Lawrence Berkeley National Laboratory and a co-author on the PNAS paper.
In this study, researchers constructed a mathematical model, based on ordinary differential equations, linking the different molecular processes associated with spine expansion together. They identified the key components (molecules and enzymes) and chemical reactions that regulate spine expansion.
As a result, they observed an interesting pattern—that the same components could both turn on and off some of the steps in the sequence—a phenomenon called paradoxical signaling. Further, they linked the chemical reactions of the different molecules to the reorganization of the actin cytoskeleton, which gives the cell its shape.
Both of these features—paradoxical signaling and linking spine expansion to actin reorganization—make this model robust, Rangamani explained. “By putting all these complicated pieces together in a simple mathematical framework, we can start to understand the underlying mechanisms of spine expansion. This is one of the benefits of combining mechanics of the cytoskeleton and biochemistry. We can bring together pieces of experimental work that are often not seen. However, we should note that we are only at the beginning stages of understanding what spines, neurons and the brain can do.”
“This work is notable for bringing together aspects from diverse disciplines (systems biology, cell signaling, actin mechanobiology and proteomics) and should motivate similar multi-disciplinary efforts for other problems in fundamental cellular neuroscience,” Khan said.
The drink is an appropriate functional beverage for the elderly
American ginseng is reported to have neurocognitive effects, and research has shown benefits in aging, central nervous system disorders, and neurodegenerative diseases. The challenges of incorporating ginseng into food are twofold: it has a bitter taste, and food processing can eliminate its healthful benefits. Reporting in the August issue of the Journal of Dairy Science®, a group of scientists has formulated low-lactose functional milk that maintained beneficial levels of American ginseng after processing. An exploratory study found the product was readily accepted by a niche group of consumers.
“Our goal was to develop low-lactose milk that could be consumed by the elderly to improve cognitive function,” reports lead investigator S. Fiszman, PhD, of the Instituto de Agroquimica y Tecnologia de Alimentos (IATA), Consejo Superior de Investigaciones Cientificas (CSIC), Patema (Valencia), Spain. “Consumers who were interested in the health benefits of ginseng rated our product quite highly.”
Because older people frequently have trouble digesting milk products, the researchers developed a low-lactose formula. American ginseng was added, and then the milk was sterilized by ultra-high temperature processing (UHT), which prolongs shelf life. Analysis found that sufficient levels of ginseng remained in the milk after treatment to improve cognitive function as reported in the literature.
To reduce the bitter taste of American ginseng, the investigators developed samples with vanilla extract and sucralose, a zero-calorie artificial sweetener. In a preliminary study, 10 tasters with a good ability to discriminate between flavors compared low lactose UHT milk without any additives (the control) to low lactose milk with ginseng extract, vanilla aroma, and sucralose added before UHT treatment. They developed a list of 10 attributes that described the sample: color, sweet odor, milk flavor, vanilla flavor, metallic/root flavor, sweetness, bitterness, aftertaste, astringency, and viscosity. They then rated the intensity of each attribute for five samples; the control; the control with ginseng extract, vanilla aroma, and sucralose added; the control with ginseng extract added; the control with vanilla and ginseng extract; and the low lactose milk with ginseng extract; vanilla aroma; and sucralose added before UHT treatment.
In a second study, 100 participants were asked, on a scale of one to five, how willing they would be to consume a “highly digestible semi-skimmed milk,” and a “highly digestible semi-skimmed milk enriched with ginseng extract that would improve cognitive function.” Then, they tasted and rated, on a scale of one to nine, the overall acceptability of the control milk and the low lactose milk with ginseng extract, vanilla aroma, and sucralose added before UHT treatment.
Both the presence of ginseng and the thermal treatment affected some sensory properties of the milk. The addition of ginseng significantly increased the perceived light brown color in the flavored and unflavored samples, and was highest in the reduced-lactose milk with ingredients added before the UHT treatment. The sweet odor was more intense in flavored samples, but decreased slightly in the samples of milk with ingredients added before UHT treatment. Bitterness was clearly perceived in the samples containing ginseng additives, but was lower in flavored samples, indicating that the vanilla aroma and sucralose masked, to some extent, the bitter taste caused by ginseng extract.
Consumer responses varied greatly, depending on interest in the product. 78% indicated that they would be likely to consume the highly digestible milk, and after tasting the product, 87% of them indicated they would buy the sample. 47% indicated they were not interested in milk enriched with ginseng, and after tasting, they gave it a low acceptability rating. However, for the 32% of consumers who did express an interest in the product, 75% declared they would buy it.
“Drinking 150 to 300 mL of this ginseng-enriched milk would provide the amount indicated to be effective for improving cognitive functions. Combined with the low levels of lactose, this makes the drink an appropriate functional beverage for the elderly,” says Dr. Fiszman. “Among consumers more likely to consume ginseng products, the newly developed milk was well accepted. The addition of more congruent flavors such as chocolate, citrus, or coffee, could be more effective in masking non-milk-related sensory attributes, Other alternatives could be investigated.”