ABSTRACT In this paper we have addressed current research regarding the effect of exercise on the brain. Future developments with regards to the treatment of mental health disorders such as depression and Parkinson’s disease have been suggested. During exercise there is a surge in Brain-Derived Neurotrophic Factor (BDNF) in the brain which promotes synaptic growth and neurogenesis in the hippocampus which can benefit the mental health of the individual. Studies suggest that BDNF is the key chemical underlying the effect of exercise on the brain. It is the stimulation of the release of BDNF which has the beneficial power; exercise is only the trigger. The brain is the hub of the human nervous system. It is made up of approximately 100 billion nerve cells which rapidly send and receive signals to and from the rest of the body. Each individual nerve cell is connected to around 10,000 other nerve cells, and it is this huge network of connections which allows signals to be transmitted through the brain so rapidly. Nerve cells are known as neurons and are made up of many dendrites leading into the cell body and one single, long axon leaving the cell body. The dendrites are thread-like branches increasing the surface area of the cell. This makes it possible for a neuron to receive many impulses at the same time. The axon is a long extension of the cell which makes it possible for an electrical signal to travel quite a long way without having to be transmitted to a new cell. It also increases the speed at which signals can travel through the brain. At the end of the axon is a collection of axon terminals, or synaptic bulbs. The spaces between the synaptic bundles and the dendrites of a second neuron are called the synapses. These are the sites where impulses are transmitted between cells. Transmission of a signal across a synapse involves the release of a chemical called a neurotransmitter, which passes from one cell to the other across the synapse. When the neurotransmitter reaches the membrane of the second cell it acts on receptor sites, changing the permeability of the membrane. In this way, the nerve impulse is transferred There are currently more than 50 known neurotransmitters, which are divided into 4 main groups. These are acetylcholine, amino acids such as gamma-aminobutyric acid (GABA), glycine and glutamate, monoamines such as noradrenaline, dopamine and serotonin, and neuropeptides such as endorphins. Different neurotransmitters have different effects on the brain and so changing levels of these chemicals can have a huge impact on brain activity. Some examples of neurotransmitters and their effects are:  Acetylcholine has an excitatory effect at the junction between nerves and muscles. As a result of this, nerve pathways which use acetylcholine as a neurotransmitter are generally involved in memory, motivation and arousal.  A shortage of the neurotransmitter dopamine can cause Parkinson’s disease, whilst increased activity of the neurons that release dopamine has been linked to schizophrenia.  Serotonin is important because it has been shown that serotonin deficiency is associated with depression, and has also been linked to other psychiatric problems such as bulimia and kleptomania. BDNF is a protein created in the brain which scientists believe causes neurogenesis in the hippocampus by promoting synaptic growth. According to Peterson’s review, “a neuron is like a tree that, instead of leaves, has synapses along its dendritic branches; eventually new branches sprout, providing more synapses to further solidify the connections. These changes are a form of cellular adaptation called synaptic plasticity, which is where BDNF takes centre stage. Early on, researchers found that if they sprinkled BDNF onto neurons in a petri dish, the cells automatically sprouted new branches, producing the same structural growth required for learning–and causing me to think of BDNF as Miracle-Gro for the brain.” It has been shown in many studies that exercise causes a surge in BDNF levels in the brain, which in turn promotes neurogenesis and improves our ability to learn and remember information. Peterson explained that researchers had participants go through intense periods of exercise, and then gave them a vocabulary learning task. They gave the same task to a control group of participants who did not exercise beforehand. Results showed that the exercise group learned new vocabulary 20 per cent faster than the control group, demonstrating a relationship between the surge in BDNF after exercise and the learning capacity of the brain. In a different study quoted by Peterson, mice were divided into four groups and each group was then allowed to run for different amounts of time. The mice were then injected with a marker that binds to BDNF to allow the researchers to monitor BDNF levels. The results of the experiment showed a direct relationship between the amount of time that the mice ran for and the levels of BDNF in their brains. Raised BDNF levels were found both in the areas of the brain associated with movement and also in the hippocampus, an area of the brain linked One theory by Reynolds is that the reason behind this lies in the fact that our ancestors had to be able to run great distances in order to survive and become more intelligent, and it is possible that because physical activity used to be so essential to our existence, it is still necessary to exercise for our brains to be able to grow and function optimally. DISCUSSION The lifelong benefits to mental and physical health from exercise have long since been known. However, recent studies have suggested that exercise has specific benefits in the brain which may lead to better memory, improved cognition and the ability to stave off diseases such as dementia, Alzheimer’s and Parkinson’s. Stem cells can be directed to differentiate into specific cell types, offering the possibility of a renewable source of replacement cells and tissues to treat diseases including patients with Alzheimer's. Embryonic stem cell research is carried out with a view to making discoveries which will bring about treatment and cures for such degenerative diseases. The use of embryonic stem cell research could lead to radical improvements in the treatment of degenerative diseases. If legal limits set on such research became less rigid, such as the 14 day limit, this could lead to more advanced discoveries of the potential use of stem cells and their regenerative and generative capacities. Perhaps stem cells gathered after 14 days would result in stem cells more capable of developing into cells which could reserve age-related degeneration. If stem cells could be produced to differentiate into neurons, they could be used to create additional pathways in the memory centre of the brain. Artificial production of BDNF could be used to stimulate this production of neurons. This may allow for increased learning and more effective memory. Research undertaken must have ethical codes in place to provide some control and any conflicts of interest must be discarded. The nature of the embryo must be considered when considering future developments of embryonic stem cell research. Issues may arise when considering the importance of the development of the primitive streak. The issue of personhood is also an important challenge to embryonic stem cell research. It is a matter of personal opinion whether one considers the embryo to be a person or potential person. The rights which should be given to the embryo are disputed by many, though it is understood that some rights should be granted as our knowledge of the activity of the brain in the early embryo is incomplete. Research conducted in 2007 has indicated that it may be possible to reverse age related macular degeneration which has caused 14 million people in Europe to become blind. Scientists believe that a treatment could be developed to cure these people of their blindness (AQA Religious Studies A2 ethics). This age related macular degeneration may also be applied to the degeneration of cells in the brain which leads to diseases such as Alzheimer’s. The neurons in the brain can become restricted in their capacity to regenerate following damage due to age related degeneration or disease. The adult brain has a limited capacity to produce new neurons. Stem cell research has the potential to lead to treatments for such degenerative diseases by replacing tissues that have little capacity for self-repair in the brain. Although adult stem cells may provide cures and treatments for diseases whilst avoiding the need for experimentation on embryos, many scientists believe that they will not offer such solutions. Embryonic stem cells are unique in that they have the ability to differentiate into almost any cell. Recent studies have shown that exercise can stimulate the production and release of hormones and proteins into the brain which can improve memory and cognition. As reported by NRPT, researchers from UC Irvine's Center for the Neurobiology of Learning & Memory studied people from 50 to 85 years old, some of whom had minor memory problems and some who did not. Volunteers viewed photographs and were then asked to ride a stationary bike at 70 percent of their maximum capacity for six minutes. Participants were given a memory test one hour after exercise which involved recalling details of the photos they had seen. There was a marked rise in memory skills in those who had exercised when compared with those who had not. This was true for cognitively impaired volunteers as well as for those who were healthy. Researchers have theorized that the improvement in memory skills may be due to norepinephrine, which is released in the brain during exercise. The studies reported by NRPT showed that inhibiting norepinephrine actually hinders memory, while raising norepinephrine levels pharmacologically can elevate memory skills. This may be due to the fact that as a stress hormone, norepinephrine affects parts of the brain such as the amygdala where attention and response are controlled. It may be that due to this increase in attention, more information can be taken in effectively and retained in the memory centre of the brain. By simulating stressful situations in a controlled environment for patients, it may be possible to stimulate the release of norepinephrine. For example, patients may be exposed to loud music and strobe lighting to stimulate the release of the stress hormone. This may be beneficial for patients with memory problems who are not able to carry out physical exercise. The improvement in memory may also help to delay the onset of some mental health disorders such as Alzheimer’s disease. However, inducing stressful situations in order to stimulate the release of norepinephrine encounters ethical issues and has drawbacks in terms of practicality. Perhaps the development of a synthetic stress hormone could be used to stimulate the same The brain starts to lose nerve tissue as we age, starting at around age 30. Aerobic exercise reinforces neural connections by increasing the number of dendrite connections between neurons, creating a denser network which is better able to process and store information. This suggests possible preventative and therapeutic effects for diseases such as Alzheimer's and Parkinson's that progress via the loss of neurons. In patients with Parkinson's disease, cells in the that contain the neurotransmitter essential for purposeful and facile muscle control, progressively die until only a small percentage remains. Studies presented by University of Pittsburgh School of Medicine researchers examined the brains of rats that had been forced to exercise for seven days before receiving a toxin that normally induces Parkinson's disease. They found that, compared to animals that had not been exercised, significantly fewer dopamine-containing neurons died. These results suggest that exercise stimulates the production of key proteins such as BDNF that are important for the survival of neurons. BDNF’s effects are not only protective, but reparative. Therefore, if a drug could be produced to stimulate the production of BDNF, it may be possible to slow down the effects of diseases such as Parkinson’s and even improve symptoms in more advanced cases. If symptoms could be reduced to the point where patients could carry out exercise it may help them to have an active part in further reducing their symptoms. Exercise classes could be introduced by the health service in communities for patient’s suffering from such diseases which would benefit from psychical exercise to help them to feel that they have more control over their illness. McGovern has established that exercise has many positive effects on our cognitive and emotional health; it is linked to lower levels of depression and anxiety and also promotes an improved ability to deal with psychological stress. Exercise has an ability to encourage neurogenesis, enhance people’s moods and reduce anxiety, and this ability stems from the way it regulates levels of neurotransmitters and other chemicals in the brain. Depression is related to low levels of neurotransmitters like serotonin and norepinephrine. Exercise stimulates the sympathetic nervous system (i.e. the fight or flight response) and so increases the concentration of these neurotransmitters. Serotonin has a reciprocal relationship with BDNF; presence of one stimulates production of the other, and since exercise also directly increases BDNF production, this reinforces the serotonin-BDNF production loop, which makes exercise a significant mood enhancer. Endorphins released during exercise have the ability to relieve both mental and physical pain, and this makes us more able to endure exercise for a longer period of time by minimising the discomfort of exercise and even causing a feeling of euphoria. The endorphins may be directly responsible for this feeling or they may just block pain and allow the pleasure associated with neurotransmitters such as serotonin to be more apparent. This link between exercise and the increased BDNF and endorphin production means that regular physical activity is strongly correlated with good mental health as people age. Exercise has such positive effects on mental health that this may become the first line of treatment for depression before the use of medication. Anti-depressant medications such as Selective Serotonin Reuptake Inhibitors like Prozac can have many mild to severe side effects. These can range from nausea and insomnia to anorexia and anxiety and in some cases treatment with Prozac has been linked to suicide. These side effects can have a severe impact on patients’ lives. Initial assessment of patients with depression to exclude an imminent suicide risk would be needed but outside this group, treatment could start with an exercise plan to follow. Exercise alone may adequately control the symptoms, thus avoiding potential side effects from medication. Drug treatment should be reserved for unresponsive cases where possible. However, motivation for exercise in those patients suffering from depressive illnesses may be lacking. CONCLUSION We are all well informed as a society on the benefits of physical exercise on our general fitness. However, many sedentary adults find it difficult to change their lifestyle or fully understand the long term benefits of consistent exercise on their mental health. Regular intervention may therefore be required as well as frequent monitoring and mentoring which may be problematic due to a lack of trained staff and funding. This problem has been highlighted by Playford (2013). She commented that `fitness instructors may lack knowledge about their conditions and how to help them participate in exercise safely`. It may be difficult to encourage frequent exercise in patients with debilitating diseases as they may feel scared or embarrassed at the prospect of engaging in physical activity. Many afflicted by the diseases discussed in this paper are over 60. It may be that the existing co-morbidities make exercise very difficult. Lateral thinking should be applied in those patients, such as arm exercises for those with knee problems. This will require funding and the expertise of individual assessments. It is important to express the benefits of exercise emphatically to patients and encourage them to engage in group exercise, ideally held by a physiotherapist or a fully trained fitness instructor used to dealing with patients with differing co-morbidities. This may be difficult to do in practice, as there is reluctance from patients to engage in group activities with strangers, and also has resource implications for primary care. We have shown that exercise is beneficial for maintenance of mental well-being. However, in practice, encouraging the group of patients who would best benefit from exercise to engage in an exercise programme remains problematic. Bowie, R. A. (2009) AQA Religious Studies A2: Ethics: Student's Book. E. D. Playford (2013) Increasing activity in patients with Parkinson’s disease. In The British Exercise and cognitive health, reported by Peterson, D. Exercise protects brains cells affected by Parkinson’s, reported by University of Pittsburgh Short Burst of Exercise Improves Memory, reported by NRPT. The Effects of Exercise on the Brain, MK McGovern Exercise and the ever-smarter human brain, reported by Gretchen Reynolds.


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Ministry Of Higher Education And Scientific Research University of Mosul College of Pharmacy Deprt. Of Pharmaceutical Science MosuL- Iraq CURRICULUM VITA PERSONAL DATA Nationality: Iraqi Current Academic Rank : Lecturer Specilization: Physical chemistry Current University : University of Mosul Current Faculty : Pharmacy Current Department : Pharmaceutical

Microsoft word - iv year.doc RAGHU College of Pharmacy IV B.PHARM. – I SEMESTER Course No. 411 – Pharmaceutical Chemistry – V (Medicinal II) 1. Physic-chemical properties of biological activity: Influence of partition coefficient, covalent bonding, hydrogen bonding, surface activity, redox potentials, chelation, enantiomerism and geometriacal isomerism on biological activity; 2. Factors

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