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A number of studies have shown that various types of stress can suppress production of new neurons in several species including humans (Lucassen et al medications major depression cheap generic chloromycetin canada. Stress is also linked to depression medicine river animal hospital discount chloromycetin 250mg fast delivery, and there is evidence of reduced hippocampus size in patients with depression, which likely reflects reduced neurogenesis (Jacobs, 2004). We noted earlier that antidepressant medication generally elevates levels of the neurotransmitter serotonin, and several studies now indicate that elevated serotonin levels increase neurogenesis. Importantly, it requires several weeks for new neurons to become integrated into functional neural pathways, and this corresponds well with the time course of antidepressant action. These drugs generally increase serotonin levels fairly rapidly, but it takes several weeks for the depression to lift, which suggests that it may be the increased birth of new neurons, rather than the elevation of serotonin per se, that is responsible for antidepressant action. If this new neurogenesis theory of depression is correct, it could lead to new and more effective treatments for this serious disorder (see Lucassen et al. When the drug wears off and monoamine activity returns to normal, these symptoms generally dissipate-a finding that further supports the link between abnormal monoamine activity and schizophrenia (see Sawa & Snyder, 2002). Although complex disorders such as schizophrenia and depression cannot be understood completely without considering a host of psychological and social factors, the biological approaches just noted have certainly improved our understanding and treatment of them. We consider the use of drugs to treat these and other disorders in more detail in Chapter 13. Unlike acetylcholine and the monoamines, these compounds were large molecules in the peptide family. Because they appeared to be, in effect, a naturally occurring morphine, they were named endorphins-a contraction of endogenous morphine. We now understand that the effects of opiate drugs are mediated through endorphinergic activity. The natural functions of the endorphins themselves are still far from clear but they certainly modulate pain relief. Glutamate is among the most abundant of the excitatory neurotransmitters and is known to be important in learning and memory processes. A thorough discussion of recent advances in neuropharmacology is beyond the scope of this text, but some developments have already had a substantial impact on our understanding of psychoactive drug actions. Indeed, many neurotransmitters have been discovered beyond those previously mentioned, and no doubt many more remain to be found. Often the discovery of a new neurotransmitter increases our understanding of drug action. For example, one neurotransmitter discovered relatively recently is a lipid called anandamide. It is of considerable interest because the active chemical in marijuana appears to act by mimicking anandamide (see Chapter 11). The Nervous System We have been focusing on a microscopic view of the nervous system as we considered how drugs might act at the level of the single neuron. We now turn to the larger picture and consider a macroscopic view of the nervous system. The sympathetic branch of the autonomic nervous system is activated during emotional arousal by a release of epinephrine and norepinephrine from the adrenal glands. This branch is responsible for the physiological changes that characterize the "fight-or-flight" reaction. During sympathetic arousal, heart rate increases, blood pressure increases, respiratory rate increases, sweating increases, pupils dilate, the mouth becomes dry, and changes occur in blood flow as blood is shunted away from the internal organs and to the brain and large muscle groups. These physiological effects are important to keep in mind because some psychoactive drugs mimic sympathetic arousal. Another group of drugs blocks a type of norepinephrine receptor in the sympathetic nervous system called "beta-noradrenergic" receptors. These beta receptors regulate blood pressure, and the so-called beta-blockers (drugs such as propranolol) are widely used in the treatment of hypertension and other vascular disorders. The other branch of the autonomic nervous system is the parasympathetic branch, which in general balances the actions of the sympathetic branch by exerting opposite effects. In contrast to sympathetic neurons, parasympathetic synapses are primarily cholinergic. Covered with tough membranes called the meninges, the brain floats within the skull in a liquid known as cerebrospinal fluid. Although weighing just a few pounds, the human brain is an extremely complex structure. The complexity of billions of neurons and more billions of synapses is absolutely staggering and almost beyond comprehension.

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Molecular biologists want to understand how the molecules within living cells contribute to cell structure and function treatment shingles buy chloromycetin with amex. Because proteins are the workhorses of cells and because they are the products of genes medicine cabinets surface mount order chloromycetin 500mg free shipping, many molecular biologists focus their attention on the structure and function of proteins or the genes that encode them. Researchers may focus their efforts on the study of just one or perhaps a few different genes or proteins. In eukaryotic species, any given cell can express thousands of different proteins, making the study of any single gene or protein akin to a "needle in a haystack" exploration. To overcome this truly formidable obstacle, researchers frequently take the approach of cloning the genes that encode their proteins of interest. The laboratory methods necessary to clone a gene were devised during the early 1970s. Since then, many technical advances have enabled gene cloning to become a widely used procedure among scientists, including geneticists, cell biologists, biochemists, plant biologists, microbiologists, evolutionary biologists, clinicians, and biotechnologists. In modern molecular biology, the diversity of uses for gene cloning is remarkable. For this reason, gene cloning has provided the foundation for critical technical advances in a variety of disciplines, including molecular biology, genetics, cell biology, biochemistry, and medicine. In this section and the following section, we will examine the two general strategies used to make copies of a gene-the insertion of a gene into a vector that is then propagated in living cells, and cloning via polymerase chain reaction. By comparison, a chromosome carries many more genes, perhaps a few hundred or thousand. Like a chromosome, a vector is replicated within a living cell; a cell that harbors a vector is called a host cell. The vectors commonly used in gene-cloning experiments were derived originally from two natural sources: plasmids or viruses. As discussed in Chapter 9, plasmids are found naturally in many strains of bacteria and occasionally in eukaryotic cells. Commercially available plasmids have been genetically engineered for effective use in cloning experiments. Another useful feature of plasmids used as vectors is they often contain resistance genes that provide host cells with the ability to grow in the presence of a toxic substance. Such a gene is called a selectable marker, because the expression of the gene selects for the growth of the host cells. However, bacteria carrying the ampR gene can grow and form visible colonies on media containing ampicillin, because they can degrade it. Viral Vectors An alternative type of vector used in cloning experiments is a viral vector. Molecular biologists may choose from hundreds of different vectors to use in their cloning experiments. This plasmid is an example of a shuttle vector, which can replicate in two different host species, E. An expression vector is designed to clone the coding sequences of genes so that they are transcribed and translated correctly. Unlike many other types of eukaryotic cells, insect cells often express large amounts of proteins that are encoded by cloned genes. When researchers want to make a large amount of a protein, they can clone the gene that encodes the protein into baculovirus and then purify the protein from insect cells. Proposed by Werner Arber in the 1960s and discovered by Hamilton Smith and Daniel Nathans in the 1970s, restriction enzymes are made naturally by many different species of bacteria. However, this interaction is not stable because it involves only a few hydrogen bonds between complementary bases. Currently, several hundred different restriction enzymes from various bacterial species have been identified and are available commercially to molecular biologists. Restriction enzymes usually recognize sequences that are palindromic; that is, the sequence in one strand is the same as that in the complementary strand when read in the opposite direction. How can an experimenter distinguish between bacterial cells that have taken up a plasmid and those that have not

This approach also results in more polyneuronal innervation oxygenating treatment order 500mg chloromycetin otc, suggesting that the pattern of activity governs which synapse will be eliminated symptoms congestive heart failure purchase 500mg chloromycetin with mastercard. Together, these experiments show that synaptic transmission can influence the process of synapse elimination. This was demonstrated by grafting two motor nerve terminals onto the same muscle in adult rats. Both nerves maintained functional connections to the muscle Use-dependent changes to adult synaptic connections occur on a regular basis, and are thought to support learning and memory (see Box 9. To take an obvious example, we speak and comprehend the language to which we were exposed as children, whether it was Tagalog, American Sign Language, or Farsi. Since direct manipulations of activity can influence synapse elimination, it is reasonable to ask whether sensory-evoked activity has an effect on the pattern of innervation. Wiesel and Hubel (1963a, 1965) performed a set of pioneering experiments that explored how visual experience impacts the maturation of connections. In these transgenic mice, motor neurons expressed either of two different fluorescent proteins. One of the motor terminals (blue) occupies a larger percentage of the postsynaptic territory at P11. It gradually withdraws from the junction (arrows) over the next 4 days, and the other terminal (green) takes over the postsynaptic site. If it was driven equivalently by each eye, then it was assigned to group four, and so forth. These histograms provide a sensitive measure of the innervation pattern in the visual cortex. This suggests that synaptic connec- tions from the nondeprived eye failed to undergo the normal process of elimination. In contrast, a greater than normal number of synapses from the deprived eye were eliminated. Reasoning that disuse must have weakened the synapses from the deprived eye, Wiesel and Hubel recorded from animals that were deprived of vision in both eyes, expecting to see a total absence of visually-evoked activity. When the synapses are close together (blue circles), synaptic elimination occurs within a few weeks. When the synapses are far apart (red circles), synaptic elimination fails to occur. At the rat nervemuscle junction, polyneuronal innervation declines between 10 and 15 days postnatal (black line). Wiesel and Hubel wrote: "It was as if the expected ill effects from closing one eye had been averted by closing the other. Taken together, these results suggest that differences in the amount of activity in the pathways from the left and right eyes determined the innervation pattern and strength of the projection from each eye. Thus, monocular deprivation creates a situation in which cortical neurons receive a set of active afferents from the open eye and a set of afferents with lowered activity from the closed eye, placing the latter at a disadvantage. In contrast, binocular deprivation evens the playing field because all afferents have a similar low level of activity. In a pivotal test of the competition hypothesis, kittens were raised with an artificial strabismus (cf. This manipulation mimics a clinical condition in humans, called amblyopia, which commonly results in the suppression of vision through one of the eyes.

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