Biology 202

2006 Second Web Paper

On Serendip

Human memory and the mechanisms of its formation are the focus of many researchers in the neuroscience field. Scientists are focusing on how the body and its hormones may regulate memory formation, as a result of external stimuli that influence hormone secretions. The research community is now focusing on diet and eating habits and their affects on chemical and hormone pathways that specifically direct human behavior. New studies support theories linking the secretion of ghrelin, in an empty stomach, to increased learning capabilities. For many years the neuropeptide hormone ghrelin was associated with appetite stimulation and function, but scientists failed to make the connection between increased ghrelin secretions and other functions. Recent discoveries have identified ghrelin's importance in increasing synaptic connections and altering neuronal morphology within the hippocampus, the neural director of memory. (1) Scientists have identified the major pathways of learning and how manipulation of these biochemical pathways can lead to improvements in memory functioning. As research continues, these new studies are linked to potential cures for memory associated diseases that can benefit from ghrelin supplements. (2) Although recent studies have found that increases in ghrelin concentration facilitate memory enhancement, the ghrelin pathways and their relationships to other hormone pathways have yet to be fully elucidated.

For many years the neuropeptide and gut hormone ghrelin has been associated with appetite and energy metabolism, but new findings support its importance in many of the body's functions. (1) Ghrelin acts as an endogenous ligand or extracellular substance that binds to receptors, primarily growth hormone secretagogue receptors (GHS). (2) Initially, ghrelin is released as a result of an empty stomach. Ghrelin is secreted from epithelial cells that line the stomach and then binds to receptors on cells located throughout the body, including the hypothalamus and the hippocampus. The release of ghrelin stimulates growth hormone release and works with the hypothalamus to illicit a hunger response. (1) Ghrelin also influences the pituitary gland, stimulation of appetite, control of energy balance, influences on sleep, gastric control, and glucose metabolism. Ghrelin's newest discovered influence lies in its ability to change synaptic connections within the hippocampal region. (3) However, ghrelin has multiple effects on metabolic and chemical pathways but how is it that these pathways interact or are interconnected? If ghrelin holds such importance in the human body, these ghrelin pathways must engage in extensive chemical communication networks, crosstalk, that involve a detailed feedback loop.
Ghrelin acts as an endogenous ligand, which binds to specific receptors located on the hippocampus that cause an increase in synaptic plasticity and the creation of new synaptic connections between neurons. (2) The biochemical effects of ghrelin induce morphological changes of the hippocampus and in turn have long lasting behavioral effects such as memory retention. These synaptic changes include underlying mechanisms such as the quantity of neurotransmitters being released into a synapse and how cells respond to those neurotransmitters. (5) The synapses are regulated by a variety of processes, which differ in the strength and enhancement of chemical signaling pathways. At those synapses that undergo repeated use, synaptic enhancement occurs, while at other less used synapses a decrease in synaptic strength can occur. (4) While memory lies within synapses of the brain, synaptic plasticity exists as a fundamental morphological function for the enhancement of the hippocampus which leads to memory retention. Perhaps the increase in synaptic plasticity within the hippocampus is a result of a dominating process that influences memory. The increase in synaptic plasticity within the hippocampus, guarantees memory efficiency and thus the body uses ghrelin to enhance the important memory process. The increase of synaptic plasticity within the hippocampus, demonstrates that the hippocampus can change synaptic form to enhance memory. This evidence introduces hope for cures for neurological diseases. However, studies have failed to discover the overlapping interplay between other ghrelin and biochemical pathways.

The increased emphasis on learning and neurodegenerative diseases by the populace, has led the scientific community to explore the underlying factors of memory. Scientists are focusing on those areas that might influence brain metabolic and synaptic capabilities. For example, scientist are considering ghrelin as a therapy for treatment in patients with Alzheimer's, a neurodegenerative disease which results in a loss of mental function due to the deterioration of brain tissue. Since Alzheimer's ultimately affects human memory retention, exogenous ghrelin supplementation could work with hippocampus receptors to increase synaptic plasticity and help memory. Further, scientists could force other tissues to express the necessary receptors for ghrelin through gene therapy and ultimately increase synapse production and function in those areas. However, many questions remain unanswered especially the complexity of the ghrelin network and its multiple roles including regulating memory, appetite, and interactions between synapses. Now that ghrelin has been identified as a major contributor to higher order brain function, total body analysis including DNA expression microarays will allow scientists to see the differences in ghrelin and ghrelin receptor expression in tissues throughout the body. With more discoveries identifying the role of ghrelin throughout the body, studies of the effectiveness of ghrelin supplementation and the negative repercussions, as a result of its interaction with other biochemical pathways, should be conducted.

The main question that remains unanswered, is how does ghrelin's effect on learning manifests itself on a larger scale? Much of the research done on ghrelin has been in mouse models, which shows their increased ability to navigate mazes, and other simple challenges. Can these findings be extrapolated to complex human learning? Further research needs to be done on human subjects, to elucidate the pathways of ghrelin and how they interact with other biochemical processes which enhance learning. It is important to remember that learning is not simply stimulated by increases in ghrelin levels and subsequent synaptic changes, but many other neurotransmitters are involved. Further, with so many pathways and more to be discovered, does ghrelin simply improve recorded memory or does the nueropeptide interact with other chemical pathways to enhance memory retention?

New challenges are arising in finding treatments for cognitive and neural degenerative disorders, and while ghrelin has a strong impact on hippocampus synaptology, ghrelin treatments themselves have not proven their medical efficacy. We cannot simply treat neurological disorders via exogenous ghrelin supplements because those ghrelin pathways have not been full characterized and therefore could interfere with other learning pathways or lead to neural pathway constrictions.

1) The Scientist: Magazine of the Life Sciences , scientific news

2) Sabrina Diano, Susan Farr, Stephen Beniot, Ewan McNay, Ivaldo Silvia, Balazs Horvath, F. Gaskin, Naoko Nonaka, Laura Jaeger, William Banks, John Morley, Shirly Pinto, Robert Sherwin, Lin Xu, Kelvin Yamada, Mark Sleeman, Matthias Tschop, Tamas L. Horvath. "Ghrelin Controls Hippocampal Spine Synapse Density and Memory Performance". Nature Neuroscience. Vol. 9, number 3 (March 2006) pg. 381-388

3) PubMed , resources about scientific research

4) arjournals.annualreview.org, Bryn Mawr College , journal reference

5) Wikipedia: References , scientific descriptions


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