| Sports-related fatigue is common in our everyday life. We know that Learning and memory are the basic requirements in whatever we do. Previous clinical and experimental studies have only proved that fatigue can affect learning and memory ability to some extents. Obvously the study still remains at the research stage, and more improvement and systematic explanation are yet to come.In this paper in-depth study of fatigue affecting the mechanism of learning and memory will be discussed boh theoretically and experimentally, in wich we will focus on the above-mentioned two parts leading to changes in learning and memory related syndromes and mechanisms of neurobiology.Previous studies showed that, PKA-CREB pathway is closely related with learning and memory. But whether the fatigue caused by changes in learning and memory is related with the pathway is not clear. Therefore, this study will clarify the role of PKA-CREB pathway for the further elaboration of fatigue which can lead to changes in learning and memory mechanism so that we can prove it with theories of the molecular biology. Also, with the intervention treatment from the Chinese proprietary medicine, we hope we can clear them of the clinical syndromes. Through a combination of the study in the animal liver, spleen, kidney on how they are connected with the relation between fatigue and memory and learning, we hope to find out the neurobiological mechanism for the syndrome research. It is expected that the study of immunohistochemistry in rat hippocampal neurons and changes in the PKA and CREB1 expression will eventually reveal the relation between the PKA-CREB pathway and the fatigue appearing in the process of learning and memory.1 TheoryThis part is mainly discussed from the clinical point of view about fatigue which results from the change in the mechanism of learning and memory. Chinese medicine has its own unique diagnosis and curing system which mainly emphasizes syndrome differentiation-different people with the same syndroms should be dealt with differently, looking for the necessary links between external factors and internal factors. Pathogenesis study is often based on human's five internal organs which in TCM is often called the study of Viscera. Rational application of the study of human's organs, blood, and other relevant Chinese meridian theory can produce a good understanding of disease mechanisms and this can help us be more aware of the pathological nature of the the disease, resulting in, of course an effective clinical function.TCM believes that the main pathogenesis of sports-related fatigue and the dysfunction of the internal organs system is a mental activity problem and can be classified as "mind" category. "Consciousness" is an important part of our life activity, and the theory of state of mind saying "there is a goddess hidden in our five internal organs " is the medical knowledge, a basic method in dealing with all kinds of diseases. Therefore we suspose fatigue led to changes in learning and memory from the relation between the body and spirit. "Mind" is, so to speak, a fine gas, a chemical and biological weapons produced by human's five internal organs. It is just through the powerful function of our organs that it can help to improve the physical performance of a person. In other words, we will be able to make a better diagnosis and treatment, improving the body organs function, thereby improving the fatigue-induced changes in learning and memory, it is provided here as a theoretical basis for clinical treatment.1.1 Understanding of the fatigue in TCMIn terms of the meaning of the word "fatigue", Traditional Chines Medicine have accumulated a lot of knowledge about it during a long period of time, knowing it mainly comes from excessive labor or overwork. From the clinical point of view, it should belong to "weary" catagory, including physical labor, stress, and too much sexual acivity. The fatigue we are talking about now is mainly the physical labor and stress. When the body does a lot of exercise, fatigue will occur in a human body, their energy will decrease, not only physically but also mentally, because physical tiredness is associated with mental stress in high tension, thus leading to a decline in learning and memory. Chinese medicine believes that when a person's physical cpndition deteriorates, their spirits, their state of mind, or their blood circulation become out of balance, resulting in tiredness, sleepiness, or a poor memory.Chinese medical theory emphasizes on "whole body treatment"wich means when treating one part of the body we should also consider other parts of the body and the syndrome differentiation, suggesting that different patients with the same symptoms should be dealt with differently. Here fatigue is a complex process, the dysfunction here can be seen as a reflection from five internal organs. To make a diagnosis, we can do it in two ways:in the first way we may look for the disorder of liver. The second we pay attention to the physical fatigue (mainiy the weariness in the patient's tendons, veins, bone, muscle, joints), or the fatigue related with their internal organs (mainly the damages done to their liver, heart, spleen, lung, kidney), or the consciousness—related fatigue (mainly about their mood changes,bad temper, or anxiety.); They can also, according to different classification, be divided into other catagories such as blood blocking, liver dysfunction and spleen. Combined with the above-mentioned classification, Chinese medicine really has the advantages of solving this problem of eliminating fatigue and recovering from physical tiredness. Learning and memory ability of the brain are advanced activities and from medical point of view, it can be classified as "spirit" or "mind" categories. "Lingshu", an ancient book about a person's life span, says:"blood and spirit has existed and, Rong Wei has been nade through, the five organs have been made, spirits and energy exist in the heart, completion of a Soul achieved, thus a human being." Also it says:"when old, the five organs are worn out, the body is running out of energy. And only the skeleton remains and eventually the last breath." Thus, spirit or mind has the ability to control, or regulate the physiological functions of the body. Whether a human's organs can function normally or not often depends on a person's state of mind and its adjustment. "Mind or spirit" is divided into broad and narrow sense. In terms of broad sense, we can say mind or spirit is the resultof all general life activities going on in the internal organs according to the general law. It is that person's vitality, and the narrow sense refers to the person's state of mind, including their feeling, consciousness, emotions, thinking and other psychological processes. Fatigue can be classified as generalized state of mind, but the process of learning and memory should go to narrow scope. Clinically, by the body language, breathing, eating, excretion, and performance of life activities, we can determine the condition of that perosn's mental performance.1.3 Understanding the relationship between fatigue amd memory according to that between a person's spirit and his/her physical appearanceChinese medicine that "soul exists in the heart, mind in lungs, sirit in the liver, will in the spleen, mood in the kidney." fully explained the relationship between the five viscera and the five emotions.Modern research has been done about the physiological fatigue including a central fatigue and peripheral fatigue which is connected with the TCM broad sense we mentioned above, and mental fatigue, which can lead to emotional changes, affecting learning and memory, and it belongs to Traditional Chinese Medicine the narrow sense. Therefore, the knowledge of the five internal organs can be used to explain the theory of a good mind set can lead to change in learning and memory affected by tiredness.2 experimental research2.1 Experiment with a rat who is tired through forced-exercisesIn the course of this study, we chose SD rats who have gone through 10 days of swimming training in the pool, establishing an animal model with exercised fatigue. This model is an ideal animal model of fatigue making rats tirerd in a short cycle doing exercise and still maintaining a higher level of exercising intensity, the rats don't have to go through the additional stress factors caused by experimental errors. This is a widely-used approach. In the modeling process, we observed the animal's weight, food intake and mental state. We found, compared with the control group,that in the the model group and the group with the Chinese Herbal Medicine, there is reduced food intake and an increase of body weight and even loss of weight at the end of experiment, This proves the model animal suffered different degrees of fatigue. After the experiment, we measured serum CK and BUN changes, and got the results that can confirm that the study a rat model of fatigue very successful.In order to study it from the perspective of Chinese medicine, we have adopted the "test with a prescription" approach, animal models were given Traditional Chinese Herbs Qi Sini which can help improve the function of liver, Sijunzitang which can improve Qi and the spleen and Jinkuishenqiwan which can help improve the function of the kidneys. We put in the intervention of Chinese medicine and observed the general condition of animals in each group and collected serum markers in different groups, so we can make sure of the fatigue related syndromes. Our results show that for more than Soothing liver, spleen, kidney, the Chinese Herbs can also have the function of improveingt different fatigue conditions. Therefore, we believe that fatigue is connected with what we TCM calls the disfunction of liver, spleen, kidney.2.2 Assessment of the rats in the fatigue affecting their learning and memoryAfter swimming training in rats with different degrees of exercise fatigue, the question of whether fatigue can surely lead to change in their learning and memory still remains to be answered in out further study. Previous theoretical studies have shown that fatigue may lead to changes in learning and memory, this change may be related to physical fatigue or mental fatigue. Our animal model in which we measured the passive avoidance response and Morris water maze test to observe changes in their memory. Through the intervention of traditional Chinese medicine for treatment of animal models, we expect to lern more about this phenomenon.Water maze test showed that the model group, when compared to normal control group, in learning and memory to swimming-out time, was significantly longer (P<0.01), error rate was significantly larger(P<0.01); the passive avoidance test showed that the model group and normal compared with the control group was significantly shorter in passive latency avoidance (P<0.01), passive avoidance failure rate was significantly increased (P<0.01). These results suggest that fatigue can lead to reduced learning and memory in rats.In the Water maze test, Traditional Chinese Medicines for liver, for spleen, for kidney, when compared with model group, their swim-out time decreased. In the passive avoidance test,the errors reduced. And the Chinese Groups of experimental animals, when compared to untreated groups, increased passive avoidance latency has increased to some extent, and in passive avoidance test the errors also decreased. The results showed that learning and memory in experimental animals treated with traditional medicines improved the most obvious. Therefore, we can infer that fatigue led to changes in learning and memory in Chinese medicine practitioners, may be closely related with liver function.2.3 Immunohistochemistry method to detect PKA, CREB1 Content Change in the model of hippocampus cellsPrevious studies showed that protein kinase A-cAMP response element binding protein (protein kinase A-cAMP response element binding protein, PKA-CREB) signaling pathway in central nervous system plays a key role, to promote nerve cell survival, regeneration, differentiation, and learning and memory are closely related. CREB is known as the memory of the "switch" in the long-term potentiation in hippocampal slices (LTP) plays the role of Chinese medicine.The formation and maintaining of the Long term memory need the synthesis of new proteins, and the first step of protein synthesis is gene transcription into mRNA. CREB as a nuclear transcription factor, regulates gene expression. CREB is a combination of the special position in the DNA, or cAMP response element (cAMP response element, CRE) of a protein. When combined with CREB and the CRE, the CRE can greatly enhance the activity of the downstream gene transcription. Regulate CREB transcription function, and phosphorylation itself will also by regulated. It is Currently known that CREB molecules is the phosphorylation of multiple protein kinase substrate. In these kinases, the first to be recognized is a protein kinase A (protein kinase A, PKA). PKA exists in the cytoplasm, consists of two identical catalytic subunit (C subunit) and two identical regulatory subunits (R subunit) component of the survival and growth of neurons and synaptic plasticity and long-term memory formation plays an important positive regulatory role.Therefore, the application of this test was determined by immunohistochemistry of hippocampal CA1 area of animal models PKA, CREB1 content changes. The results with the positive reaction of the average optical density (MOD) suggests that in order to determine whether the pathway involved in learning and memory caused fatigue changes, and to explore the associated syndromes.Experimental results show that the model group of PKA and CREB 1 positive reaction in the hippocampus than the control group were significantly lower, while training plus medicine group and model group all have different degrees of increase, in order to improve the Liver Unit more apparent.The following conclusions are made through the theoretical and experimental research1 An animal experiment showed that fatigue can lead to learning and memory decline;2 PKA-CREB signal transduction pathway involved in the fatigue caused changes in the regulation of learning and memory and learning and memory formation of the positive role of regulation;3 By improving a liver, spleen, kidney function with Chinese herbal formula (Si Ni San, Sijunzitang and Jinkuishenqiwan) to intervene in the animal models, results showed that the fatigue resulting from lower learning and memory ability and in medicine liver, spleen, kidney dysfunction, but not with liver more closely. |
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