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| Immune, Nervous, and Reproductive Systems Part II: The Nervous System |
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In describing the nervous system and the aging process, it is easiest to divide up the nervous system in to each of its components. We will study the senses, the peripheral nervous system, and the central nervous system (brain and spinal cord). Each of these sections will discuss normal functioning, aging and age-related disease. In the final analysis we will attempt to bring it all together by discussing the interactions that occur between each component (i.e. sensation, central nervous system integration and response generation) to produce behavioral modifications associated with aging. |
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The senses are our environmental detectors. They let us know about light,
sound, odors, tastes, heat, pressure to our skin and movement of our bodies.
The detection of environmental information is mediated in each of these
senses through a specialized type of nervous system cell called a sensory
receptor. Sensory receptors behave identically to the basic cell type
of the nervous system called the neuron, except each sensory receptor
has a developed component of the cell for detecting environmental information.
We will describe each of these specialized receptors for each of the senses
below. Below we have listed the senses with the environmental information
they are specialized to detect.
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| Vision We have both black and white photoreceptors knows as rods and color receptors known as cones. The photo pigment found in rods is rhodopsin and the photo pigment found in cones is iodopsin. Absorption of this energy causes a cascade of events that leads to the activation and discharge of the visual receptor. This message is then sent through many neural links to eventually activate neurons found in the visual cortex located in the back of the head. These cells and all of the other cells are highly active and utilize huge amounts of energy (glucose) and the eye is therefore highly vascularized to enable the rapid supply of fuel to the eye. The visual receptors are located in the back of the eye in a region called the retina. The retina has both rods and cones and there is a special region of the retina called the fovea that has the highest visual acuity and is made-up almost exclusively of cones. The fovea is a specialized component of the macula which also contains a very high percentage of cones. When we focus on something, we are focussing the rays of light onto the fovea. The photoreceptors of the retina connect to a number of other neurons where a series of processing steps occur before the information ever leaves the eye. The image is focused on the fovea by a precise bending or refraction of the light by the most outer covering of the eye, the cornea, and by the lens which is made up of a protein called crystalline. The water bodies between the cornea and the lens (anterior chamber filled with aqueous humor) and the lens and the retina (vitreous humor) also contribute to some of the light refraction. Any change in the shape of the cornea or lens will displace the focus of the image. |
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The age-related changes that occur in the visual system can be divided into the optical component (i.e., the lens and cornea) and the receptive or visual component (i.e., the retina). With aging, the cornea becomes thicker and less curved with age making the eye more susceptible to astigmatism (defective curvature which results in inconsistent focusing). The other major change is in the lens. The lens tends to harden and increase in opacity with age. The increase in opacity alters light refraction causing a scattering of light. Opacity may also alter color vision slightly. When opacity becomes severe, the result is a cataract. In cataracts the scattering of light and loss of acuity can be so great as to result in functional blindness. The cataract must be removed for vision to return. The other major age-related change occurring in the lens is a loss of elasticity. The crystalline proteins in the core of the lens are produced at birth and stay with us for our entire lives. Aging causes opacity and cross-linking of these proteins to decrease their flexibility. This change is due in part to the damaging effects of ultra-violet (UV) radiation. To guard against the UV damage we are encouraged to plastic or glass lenses to help to filter out the UV rays. A loss of flexibility can limit the ability of the lens to roundup or accommodate when we try to focus on near objects. We can see images far away, but not near. We become hyperopic or farsighted. All humans experience this change and most will require reading glasses after the age of 55. This age-related loss of accommodation is called presbyopia. The optical properties of the lens can be changed through
Although not part of the sensory system, the size of the pupil (determined by the contraction of the iris) becomes smaller as we get older. The ability of the iris to contract and increase the size of the pupil in dark conditions is most affected. The consequence of this change in pupil function is less light is let into the eye in dark conditions. In addition, there are changes in the functions of rods (i.e. decrease in rhodopsin pigment) that dramatically raises the threshold for detecting light. The end result of these changes is that older people have more trouble adapting to changes in light levels (dark adaptation) and they have less acuity in the dark. Age-Related Diseases of the Eye We have already discussed the most common visual disorder of the elderly, cataracts (see above). The second most common disorder is glaucoma. Glaucoma results when the intraocular fluid pressure becomes so great that it disrupts the major nerve leaving the eye with visual information. This is followed by a cutting off of the oxygen and resulting blindness. It is cured by relieving the pressure. The most common treatment is eye drops (Miotics) containing pilocarpine or beta-blockers (i.e. Timolol). The most devastating eye disease is senile macular degeneration. The macula is responsible for our color vision and it contains the fovea which is critical for focusing images and obtaining the greatest visual acuity. Macular degeneration has a hereditary component and it occurs mostly in women. It is associated with vascular damage and some cases may be treated with laser photocoagulation. Another disease that commonly results in blindness is diabetes. The vasculature of the eye is highly sensitive to diabetic pathology and the blood vessels of the eye can either become occluded or proliferate to result in blindness.
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Sound moves through the air in waves that result from the compression and collision of adjoining air molecules. Different sounds result from the movement of the air particles at different frequencies. Ultimately the air molecule movement will reach the eardrum (tympanic membrane) of the middle ear causing a compression and movement of the eardrum. The ear drum is attached to the bones of the middle ear (hammer, anvil and stirrup) which religiously follow the frequency and depth of the movement of the ear drum. The stirrup attaches directly to the receptive organ of the ear, the cochlea, at a specialized zone called the oval window. The cochlea is filled with fluid and movement at the oval window sets the fluid into motion in a fashion that is coded for the intensity and frequency of movement experienced by the ear drum. The receptor cells of the cochlea are called hair cells for the hair like projections they send up into the gelatinous fluid filling the cochlea. There are approximately 20,000 hair cells found within the organ of corti positioned in each cochlea and they are arranged in rows of three. The receptors genetically determined to respond to high frequency sounds are located closest to the oval window and the ones designed to detect low frequency sounds are the furthest away from the window. The cochlea looks like a snail shell, with the low frequency receptors all rolled up in the center of the shell. Movement of the fluid in the cochlea causes movement of the hair-like projections which causes the hair cell to discharge (if the movement was at the correct frequency) and send its information out the auditory nerve and into the brain for processing. Aging and Hearing A loss of hearing associated with aging is referred to as presbycusis. The most common age related change in hearing is a reduced sensitivity or loss of detection of high frequency sounds. This age-related change is due mainly to the damage and loss of hair cells destined to perceive the high frequency sounds. More rarely, changes in the cochlea structure can also cause this type of hearing loss. These changes can impair our ability to localize sounds, especially if our ears are not equally effected. The loss of high frequency perception also disrupts our ability to perceive and understand speech. This decline is most marked when the person is speaking quickly or with echoes and disruptions as is often encountered in crowded rooms. Hearing loss is determined through an audiogram. Most age related hearing impairment can be treated successfully with haring aids. Over the last few decades there has been a market improvement in the quality of these devices. Most recently, digital hearing aids have been introduced which are a great improvement over analog devices. |
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Our vestibular apparatus (motion detector) which consists of the utricle and saccule (gravity detectors) operate similarly to the cochlea. They are found in the middle ear area and are located in fluid filled chambers. Movement of the fluid causes movement of the hairs projecting up from the hair cells. These hair cells discharge and send information about the direction and speed of our movement as well as the position of our head with respect to gravity. The membranes of the utricle and saccule actually have a number of small rocks called otoliths imbedded in them and they push down upon the underlying receptors to infer information about gravity. |
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Vestibular dysfunction is manifested by a feeling of unsteadiness, disequilibrium and sometimes vertigo and nausea. Like all sensory cells (except taste receptors) loss of vestibular hairs cells is final. With aging there is some loss of hair cells which impairs the message sent to the brain. These cells are also extremely vulnerable to vascular problems and will easily die if the blood supply is cut off. There are some reports of up to a 50% loss of nerve fibers leaving the vestibular organs in individuals over the age of 70. In extreme cases, some individuals will experience vertigo or dizziness with certain head positions. The only treatment is to train the patient to avoid the head positions or rotations. Diseases of Aging of the Vestibular Apparatus A common disease that occurs in the vestibular system is Meniere's disease. It usually starts with nausea, vomiting and severe loss of balance. Individuals with this condition are sometimes confined to their beds for weeks. This diseases can last for weeks and even months. However, there are medications that can be used to successfully treat this condition. |
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The sense of smell is incredibly important. It is crucial for deriving pleasure from the environment (i.e. spring time, flowers) and an essential component of the pleasure derived from eating. Problems in smell can often result in malnutrition and lead to a lack of interest in eating. The sense of smell also helps protects us from the consumption of spoiled foods and warns us when leaks in household gases exist.
Olfactory receptors located in the olfactory mucosa of our noses have specialized proteins on their exterior that function to detect different air-born molecules (smells). Every receptor is specialized in that it has a different set of protein detectors on it's surface. When one of these proteins grabs on to an odor molecule it causes the olfactory receptor to discharge and send the information to the brain (the olfactory cortex located just above the nose). |
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As we get older we lose sensitivity (we require more odor to detect it) and we also lose our ability to discriminate between odors. As early in life as when we were toddlers we begin to show changes in our olfactory epithelium. We actually lose sensory cells and they are not replaced. At age 25 we have 50,000 olfactory receptors (mitral cells), at age 60 we have 30,000 and by age 90 we are left with 15,000. This loss of sensory cells underlies the decrease in sensitivity associated with age. Environmental exposure to volatile or noxious agents can accelerate the cell loss. |
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Much like the sense of smell, we rely upon taste to tell us whether something is good or bad to eat. Taste receptors have specialized proteins on their surface (also called receptors) that detect different molecules that are dissolved in our saliva. Taste receptors are unique cells in the nervous system in that new ones are cycled in about once every eight days. No other sensory system or other component of the nervous system possesses this ability to regenerate. These taste receptor cells collect together in bunches of 40-50 cells to form flask shaped taste buds. |
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Compared to the sense of smell, aging changes in taste are minor due in part to the regenerative ability of the sensory cells. Nearly 50% of taste buds are lost between the ages of 30 to 60 resulting in a decline in taste sensitivity with age. This change can affect the nutritional status of the elderly since a big part of the drive to eat and obtain nutrition is the pleasure that comes from taste. |
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The sensation of touch, pressure, heat and cold, vibration, pain, and positioning of our limbs and muscles (proprioception) are all produced by receptors located in the skin, joints and muscles. Each modality is detected by specialized sensory cells specific to the environmental stimuli. Generally, all show some sort of decline with age. Some can be accounted for by central - perceptual changes, but much of the functional change can be attributed to loss of skin receptors. Problems with proprioception can also contribute to an increase in unsteadiness and falls. Decreases in the sensitivity to heat and pain can mean that the person will experience more tissue damage before they remove themselves from the harmful stimulus (e.g., burn). This increase in skin damage is then compounded by the slowing in healing rate of the aged skin and the increased vulnerability of the skin to infection with age. |
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Individual cells responsible for mediating communication in the nervous system are called neurons. Compared to other cells found in our bodies, neurons have an incredible complicated architecture. Like all cells, neurons have a central cell body that contains a nucleus and the biochemical machinery for making new proteins. The neuron is unique in that it has a number of very long processes emanating from the cell body, called dendrites, that serve as antennae for receiving inputs from hundreds or even thousands of other nerve cells. Each of the contacts made by other nerve cells onto the receiving nerve cell's dendrites is called a synapse. The neuron receiving all this information will integrate all the signals and, if they are important enough, they will cause the neuron to produce an electrical discharge known as an action potential. The axon acts like an output cable and links the neuron with the next neuron in the circuit to be recruited for the expression of a behavior, thought or physiological response. Axons can be as short as 1/100th of a mm or as long as a meter. For example, when you make the decision to move your foot, a group of neurons in the outer shell of your brain known as the cortex will send an electrical message (action potential) down their axons which travel out of your head and down your spinal cord to make contact (synapse) with a motor neuron located in your spinal cord at the level of about the bottom of your rib cage. This is an incredibly long distance, but the message travels quickly. When you recruit a number of neurons to produce a behavior (for example 20 cells recruited in sequence) the time it takes to produce the behavior is referred to as your reaction time. For example let's look at what it takes to react to a red light when you are driving. When you see an object in front of you when you are driving or when the signal changes from green to red, the information has to travel from your eye to a series of relays until it reaches the specialized part of the cortex called the visual cortex located at the back your brain. The neurons of the visual cortex then send this to another part of the brain to make sense of the image (associational cortex). The information is integrated and a decision is made about what to do about the image you just saw (i.e. red light). Once that decision is made a cast of neurons send their output signals to the motor neurons designated to control leg and foot movements (again in the cortex) and, if the signal is strong enough, the motor neurons send their message to the second set of motor neurons found in your spinal cord. These cells are then activated and they send their message to the muscles of the foot and leg causing the foot and leg to move and place your foot on the brake. |
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Aging and the Central Nervous System It has been demonstrated in almost every animal studied that the speed with which the signal travels down the axon of each neuron is slowed as a function of age (slowing in conduction velocity). It is estimated that the conduction velocity can decrease by as much as 30% over the life span, with reports of 10-40% decreases in conduction velocity. On an individual cell basis it may not seem like much, but when the effect is additive over many hundreds of neurons involved in a circuit it has the behavioral outcome of slowing reaction time. We have already seen that speech spoken rapidly becomes more difficult to understand with age. Part of this problem in understanding rapid speech stems from the slowing in nerve cell conduction velocity. In general, this basic change can contribute to an overall slowing in cognitive processing. To get a feel of the effect now would be a good time to refer to exercise below. When we look at the overall brain in aged individuals we that there is a steady loss in brain mass that becomes noticeable after the age of 40. Over the life span it is reported that we may lose as much as 10% of our brain mass. This change in not necessarily due to a loss of nerve cells, which appears to moderate, but rather due to a shrinking of nerve cells. Studies have demonstrated that the dendrites of nerve cells in the oldest population tend to be shorter and less complicated. The number of contacts or synapses also appears to decrease. These change indicate that there is less transfer of information between neurons experiencing these regressive changes. If we look inside the cells there is some evidence of neurofibrillary tangles and neuritic plaques in normal aging, but not to the extent seen in Alzheimer's disease. There is also an increase in the number of supportive, non-communicating cells known as glia in the brain of older people. Glial cells are crucial for eliminating waste and performing debridement. |
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Age-Related Diseases of the Brain Nerve cells of the brain do not get replaced (regenerate) if they are lost. In the case of small losses, there is enough redundancy in nerve cell function to allow for neighboring nerve cell to take over the duties and compensate for the small loss. If the nerve cell loss is extensive, however, permanent behavioral modifications will occur. Parkinson's Disease is caused by an extensive loss of a very small population of neurons located in the midbrain (just above the junction between your neck and head) which use a specific neurotransmitter, dopamine. While these neurons are not numerous, they have a widespread effect on brain function through the many axons they send throughout the brain. The neurons are located in a very specific and small band called the substantia nigra (black substance). The disease is progressive through the gradual loss of these cells. Parkinson's disease occurs in 1 of every 100 people over the age of 60, with approximately 1.5 million Americans presently diagnosed as having Parkinson's disease. It is estimated that 50,000 new patients will be diagnosed each year.
The most common treatment is SINAMET which is a combination of L-dopa and an inhibitor of the enzyme that usually digests dopamine once it has been released. The strategy behind L-dopa therapy is that dopamine neurons use L-dopa to make dopamine, so if you give them more L-dopa they will make more dopamine. Thus despite the loss of dopamine containing and releasing neurons, the remaining dopamine cells will make more and release more dopamine if given L-dopa and their increased release will compensate for the loss of neighboring cells. The problem is the disease is progressive and as more and more cells die the L-dopa therapy becomes less and less effective. Other strategies involve the blockage of an enzyme that causes oxidation with a drug called Deprenyl or Eldepryl. By reducing free radical production it slows the progression of the disease. Surgery while it cannot cure the disease, may assist in the treatment of certain symptoms. The brain often works through apposing systems, like ying and yang. With the loss of the substantia nigra, another system in the brain called pallidum becomes overactive. Surgeons have found that pallidectomy (removal of the pallidum) is quite effective in alleviating the rigidity of Parkinson's disease. |
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Alzheimer's disease is a disease of survivors affecting the oldest old except for the rare familial cases. It was estimate in 1994 that over 4 million Americans had Alzheimer's disease. There is no successful way to prevent or cure this disease, and it is estimated by the year 2020 there will be 15 million individuals with Alzheimer's disease. The prevalence increases with age with 5% over the age of 65, 10% over 75, 33% over 85 afflicted with the disease. The prevalence doubles every 5.1 years after the age of 65. An extremely rare form of Alzheimer' Disease (5% of cases) is inherited as an autosomal dominant gene. There are several environmental risk factors that may affect the risk of Alzheimer disease. It has been shown that the chronic use of anti-inflammatory drugs (for example for arthritis) reduces the risk for AD by as much as 60% if taken consistently for a period of over 2 years. This include the nonsteroidal anti-inflammatory drugs (NSAIDs) motrin, ibuprofen and aleve. Mental stimulation also appears to reduce the risk for AD with the lowest incidence of AD in those who went to college and professional schools. High risk factors include prior head injury, low levels of education and occupational exposure to glues, pesticides and fertilizers. For women, a large risk factor is lack of estrogen. Estrogen appears to protect the brain from AD and there is evidence that estrogen supplementation therapy (Premarin) reduces the risk of AD by as much as 50%. Present therapies for AD are limited. First, cognitive retraining is encouraged. The patients need to have their entire lives structured. Drugs that have had limited success include Tacrine and Aricept. The diagnosis of dementia is made through neurological and psychological testing which detect cognitive impairment. Other conditions that stimulate dementia need to be eliminated before a diagnosis of Alzheimer's Disease can be made. The ultimate diagnosis of senile dementia of the Alzheimer's type is through the postmortem identification of of neurofibrillary tangles and neuritic plaques. The following is a quick list of other causes of dementia that are not of the Alzheimer's type:
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Lastly, we would like to end with a short discussion of stroke. It is estimated that over 500,000 Americans will suffer a stroke next year. Stroke result when the oxygen supply is cut off to the brain. The most common cause is when small infarcts or occlusions occur and there may no immediate behavioral consequence. If this process continues, however, the summed effect of many small strokes can be devastating (multi-infarct dementia). Large strokes have a more immediate effect. They can cause paralysis, deafness, loss of speech, functional blindness and anything else perceived by or performed by the brain. The reason for the specific loss of select functions with stroke is the regional specialization of the brain. Distinct regions of the cortex are designated for the perception of touch, pain, sound, taste, and light. Other regions are designated for the perception of language, while others are designated for the production of language. We have provided a model of the brain illustrating the regional specialization of function in class exercise A. The warning signs of a stroke include:
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The Senses
Central Nervous System
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| Click here to go to Lecture Part III: The Reproductive System |
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The
diagnosis is based upon the behavioral consequences and the responses
to drug therapies. The acronym TRAP is used to describe Parkinson behavior
standing for - tremor, rigidity, akinesia (slowing of movement), postural
instability. Patient also show a shuffling step, a lack of facial expression
and weak voice, and some cognitive - frontal lobe dysfunction which
affects personality, consciousness, attention, and abstract thinking.
The cause is speculative at this point. Most research suggests an environmental
cause, although there is a rare early onset form that is inherited.
The suggested environmental causes include head trauma and vascular
damage, heavy metal toxicity, excess excitation leading to cell death
and free radical damage of cell molecules leading to cell death.