By X. Merdarion. Saint Petersburg College.
At autopsy cheap 160mg malegra dxt plus with amex, patients with Parkinson’s disease superior cerebellar peduncles generic malegra dxt plus 160 mg amex. Input to the cerebellum show a severe loss of dopamine-containing neurons in the comes from peripheral sensory receptors buy generic malegra dxt plus 160mg on-line, the brainstem buy 160mg malegra dxt plus with visa, SNc region. The inferior, middle and, to a lesser controllable, quick, brief movements of individual limbs. The These movements are similar to what a normal individual output projections are mainly, if not totally, to other motor might show when flicking a fly off a hand or when quickly control areas of the central nervous system and are mostly reaching up to scratch an itchy nose. One theory is that the primary action is to schemes, the interposed nucleus is further divided into the inhibit undesirable movements, thereby, allowing desired emboliform and globose nuclei. Neuronal activity is increased in the appropriate areas of the basal ganglia prior to the actual ex- ecution of movement. The basal ganglia act as a brake on The Structural Divisions of the undesirable motion by the inhibitory output of the GPi Cerebellum Correlate With Function back to the cortex through the thalamus. The loss of The cerebellar surface is arranged in multiple, parallel, lon- dopamine-releasing neurons in Parkinson’s disease is gitudinal folds termed folia. Several deep fissures divide the thought to produce this type of result by reducing in- cerebellum into three main morphological components— hibitory influence on the striatum and, thereby, increasing the anterior, posterior, and flocculonodular lobes, which the excitatory action of the subthalamic nucleus on the GPi also correspond with the functional subdivisions of the through the indirect basal ganglia pathway (see Clinical cerebellum (Fig. Hyperkinetic disorders like Huntington’s vestibulocerebellum, the spinocerebellum, and the cerebro- disease are thought to result from decreased GPi output cerebellum. Loss of dopamine-producing neurons in the sub- small probe can be precisely placed into a target within stantia nigra pars compacta is the cause of the condition. Magnetic resonance imaging (MRI) of the brain Treatment with medications that stimulate an increased defines the three-dimensional location of the GPi. The production of dopamine by the surviving substantia nigra surgical probe is introduced into the brain through a neurons has revolutionized the management of Parkin- small hole made in the skull and is guided to the target son’s disease. Unfortunately, the benefit of the medica- by the surgeon using the MRI coordinates. In- positioning of the probe into the GPi can be further con- creasing difficulty in initiating movement and worsening firmed by recording the electrical activity of the GPi neu- slowness of movement are features of a declining respon- rons with an electrode located at the tip of the probe. Improved knowledge of basal gan- neurons have a continuous, high frequency firing pattern glia circuitry has enabled neurosurgeons to develop surgi- that, when amplified and presented on a loudspeaker, cal procedures to ameliorate some of the effects of the sounds like heavy rain striking a metal roof. The inhibitory outflow of the GPi is reduced and Inhibitory output of the putamen to the GPe greatly in- movement improves. This results in decreased The use of implantable stimulators to modify activity of inhibitory GPe output to the subthalamic nucleus, which, the basal ganglia nuclei is also being investigated to im- in turn, acts unrestrained to stimulate the GPi. Stimulation prove function in patients with Parkinson’s disease and of the GPi enhances its inhibitory influence on the thala- other types of movement disorders. CHAPTER 5 The Motor System 105 Intermediate fastigial and interposed nuclei contain a complete repre- Vermis zone sentation of the muscles of the body. The fastigial output Lateral system controls antigravity muscles in posture and locomo- zone tion, while the interposed nuclei, perhaps, act on stretch re- Primary flexes and other somatosensory reflexes. Input comes exclusively from the cerebral cortex, relayed through the middle cerebellar pe- duncles of the pons. The cortical areas that are prominent in motor control are the sources for most of this input. Output Posterior lobe is directed to the dentate nuclei and from there via the ven- trolateral thalamus back to the motor and premotor cortices. The Intrinsic Circuitry of the Cerebellum Is Very Regular The cerebellar cortex is composed of five types of neurons Posterolateral arranged into three layers (Fig. The molecular layer fissure Flocculonodular lobe is the outermost and consists mostly of axons and dendrites plus two types of interneurons, stellate cells and basket cells. The next layer contains the dramatic Purkinje cells, whose dendrites reach upward into the molecular layer in a IP F D fan-like array.
NEUROTRANSMITTER CHANGES IN AzD The NT most consistently implicated in AzD is ACh cheap malegra dxt plus 160 mg line. ACETYLCHOLINE It is 20 years since a 50% reduction was noted in the level of choline acetyltransferase (ChAT) buy 160 mg malegra dxt plus with mastercard, the enzyme responsible for ACh synthesis buy discount malegra dxt plus 160 mg line, in the frontal cortex and hippocampus of AzD patients (Bowen et al malegra dxt plus 160mg with amex. ACh itself was not easily measured at that time but a reduced synthesis of ACh from 14C glucose was observed in brain tissue from AzD patients. There is in fact a significant correlation between the reduction in ChAT and both the increased number of plaques and tangles at death and the severity of mental impairment six months before death (Perry et al. ACh loss is not global, no change being found in the striatum or some parts of the cortex. Recently reduced ACh levels have been reported in CSF obtained by lumbar puncture, though it is surprising that it survived degradation (Tohgi et al. Since ACh is mostly synthesised in nerve terminals, the reduction in cortical ChAT must reflect a loss of cholinergic nerve terminals and as there are few cholinergic neurons in the cortex, these must be the endings of axons that come from cholinergic neurons in the subcortical nucleus basalis (Fig. In fact there is a dramatic loss (570%) of such neurons in AzD, especially in younger patients, although there is some evidence that the loss of cortical ChAT is greater than the cell loss and that degeneration starts in the cortical terminals and proceeds retrogradely to the cell bodies. Plaques and tangles are also found in the nucleus basalis but lesion of it does not induce their formation in the cortex and their cortical location does not just coincide with cholinergic innervation. No overall reduction in cholinergic muscarinic receptors was found but recent studies with relatively specific ligands show a loss of presynaptic M2 receptors, in keeping with the loss of terminals, but no reduction in postsynaptic M1 receptors. ACh AND b-AMYLOID Low concentrations of solubilised b-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of Ab below those generally neurotoxic. Since b-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism). To what extent these events can occur in vivo, let alone with insoluble b-amyloid, which forms the plaques, is not clear but soluble b-amyloid itself is also increased significantly in AzD brain and when infused into the ventricles of rats reduces ChAT activity. MONOAMINES Of course, cholinergic neurons are not the only ones with axon terminals in the cortex and if their degeneration does originate in the cortex then other afferants and their neurons could also be affected. This contention is supported by reported reductions in the number of NA neurons in the locus coeruleus, and 5-HT neurons in dorsal raphe but these are less marked (approximately 50%) than the loss of cholinergic neurons. Accompanying reductions in cortical NA and 5-HT are also seen but are again lower than those for ChAT but 5-HT2 receptors are reduced (43%). SOMATOSTATIN Among a number of peptides studied it is only the reduction of somatostatin in the temporal, parietal and frontal cortices that correlates with the severity of dementia in AzD, although corticotrophin-releasing factor is lower. Reductions in somatostatin do not generally parallel those of ChAT, its concentration being almost normal in the hippocampus and nucleus basalis, where ChAT levels are lowest and there is no evidence that it is localised in cholinergic neurons. GLUTAMATE Despite the loss of cortical pyramidal cells no reduction in glutamate levels has been found generally in AzD, except in parts of the hippocampus where the density of glutamate nerve terminals is very high. Here the NT pool could form a sufficiently major part of the total tissue content that any reduction in that measure would indeed reflect a loss in NT glutamate. A reduction in the sodium-dependent D-[3H] aspartate binding, which is presumed to label glutamate nerve terminals, has been shown for some (e. This picture is also complicated by the binding of aspartate to glial cells that multiply to occupy lost neuronal space. Although there are some reports of a reduction in the number of glutamate NMDA receptors in the hippo- campus, this has not been found generally in the cortex. Some of the symptoms of AzD are similar to those seen in patients with cortico- cortical disconnection, i. These include difficulties in recognising known objects through sensory inputs such as touch or smell (agnosia), producing or understanding spoken or written words (aphasia), and initiating or performing familiar movements (apraxia). All these impairments show not only a loss of memory but also an inability to link (associate) the activity of different cortical functions and areas.
If weight C (to- spond to the force and shortening records during the lifting of tal weight A B C) is added to the afterload malegra dxt plus 160mg amex, the muscle those weights purchase 160mg malegra dxt plus with amex. In each case buy malegra dxt plus 160mg cheap, the adjustable platform prevents the cannot lift it order malegra dxt plus 160 mg free shipping, and the entire contraction remains isometric. If the muscle has not been stimulated, this resisting force is called passive The types of contraction described above provide a basis force or resting force. The isomet- The relationship between force and length is much dif- ric and isotonic mechanical behavior of muscle can be de- ferent in a stimulated muscle. The amount of active force or scribed in terms of two important relationships: active tension a muscle can produce during an isometric • The length-tension curve, treating isometric contraction contraction depends on the length at which the muscle is at different muscle lengths held. At a length roughly corresponding to the natural • The force-velocity curve, concerned with muscle per- length in the body, the resting length, the maximum force formance during isotonic contraction is produced. If the muscle is set to a shorter length and then stimulated, it produces less force. At an extremely short Isometric Contraction and the Length-Tension Curve. If the muscle is made Because it is made of contractile proteins and connective longer than its optimal length, it produces less force when tissue, an isolated muscle can resist being stretched at rest. This behavior is summarized in the length-ten- When it is very short, it is slack and will not resist passive sion curve (Fig. Normally a muscle is force produced by a series of twitches made over the range CHAPTER 9 Skeletal Muscle and Smooth Muscle 161 Passive Total force 5 4 3 2 1 0 0 7 8 9 Time Length Active 9 8 At length 8. Subtraction of the passive curve from the total curve Time yields the active force curve. These curves are further illus- Passive trated in the lower right corner of the figure. Everyday experience shows that the speed at which a mus- The total peak force from each twitch is related to each cle can shorten depends on the load that must be moved. The muscle length is changed only Simply stated, light loads are lifted faster than heavy ones. The difference between the into how the force and shortening of muscles are matched total force and the passive force is called the active force to the external tasks they perform, as well as how muscles (see inset; Fig. The active force results directly from function internally to liberate mechanical energy from their the active contraction of the muscle. The analysis is performed by arranging a The length-tension curve shows that when the muscle is muscle so that it can be presented with a series of afterloads either longer or shorter than optimal length, it produces (see Fig. Myofilament overlap is a primary factor in deter- stimulated, lighter loads are lifted quickly and heavier loads mining the active length-tension curve (see Chapter 8). If the applied load is greater than the maximal However, studies have demonstrated that at very short force capability of the muscle, known as Fmax, no shorten- lengths, the effectiveness of some steps in the excitation- ing will result and the contraction will be isometric. If no contraction coupling process is reduced—binding of cal- load is applied, the muscle will shorten at its greatest possi- cium to troponin is less and there is some loss of action po- ble speed, a velocity known as Vmax. The initial velocity—the speed with which the muscle The functional significance of the length-tension curve begins to shorten—is measured at various loads. Many skeletal locity is measured because the muscle soon begins to slow muscles are confined by their skeletal attachments to a rel- down; as it gets shorter, it moves down its length-tension atively short region of the curve that is near the optimal curve and is capable of less force and speed of shortening. In these cases, the lever action of the skeletal sys- When all the initial velocity measurements are related to tem, not the length-tension relationship, is of primary im- each corresponding afterload lifted, an inverse relationship portance in determining the maximal force the muscle can known as the force-velocity curve is obtained. Cardiac muscle, however, normally works at lengths steeper at low forces. When the measurements are made on significantly less than optimal for force production, but its a fully activated muscle, the force-velocity curve defines passive length-tension curve is shifted to shorter lengths the upper limits of the muscle’s isotonic capability. The length-tension relationship is, there- tice, a completely unloaded contraction is very difficult to fore, very important when considering the ability of cardiac arrange, but mathematical extrapolation provides an accu- muscle to adjust to changes in length (related to the volume rate Vmax value. The role of the length-tension curve in smooth a series of isotonic contractions. The initial velocity points muscle is less clearly understood because of the great di- (A–D) correspond to the contractions shown at the top.
With further encir- cling buy malegra dxt plus 160mg online, the inner protein layers of the cell membrane make contact as well and fuse to form the dense major period line (A5) malegra dxt plus 160 mg amex. At the end of the process buy 160mg malegra dxt plus amex, the start of the duplica- tion lies inside the myelin sheath generic malegra dxt plus 160 mg with mastercard, the inter- nal mesaxon (AB6), while the end lies out- side, the external mesaxon (7 in A, B). Development of Unmyelinated Nerve Fibers (A) Unmyelinated nerve fibers (A8) are en- veloped by sheath cells, each of which en- circles several axons. The margins of the grooves may also form a membrane dupli- cation (mesaxon) but without fusion of the membrane layers. Myelin Sheath 39 4 6 7 1 3 5 2 8 A Development of the myelin sheath (according to Hamilton, Boyd and Mossman) 9 10 7 6 12 B Central nerve fiber, electron-microscopic diagram (according to Bunge) 11 C Oligodendrocyte with myelin lamellae (according to Bunge) Kahle, Color Atlas of Human Anatomy, Vol. This mode of conduction is much borders on a basal lamina (AB2), which en- faster and requires less energy than the con- velops the entire peripheral nerve fiber. The Schmidt–Lanterman The peripheral nerve fiber is surrounded by clefts (A4) are depicted in longitudinal sec- longitudinal collagenous connective-tissue tionascytoplasmiccrevicesofthemajorpe- fibrils; together with the basal membrane, riod lines. The struction, they appear as spirals in which nerve fibers are embedded in a loose con- the cytoplasm communicates between the nective tissue, the endoneurium (D8). At the node of Ranvier able number of nerve fibers is collected into (B5), the Schwann cell processes (AB6) slide bundles or fascicles (C10) by the perineurium over the paranodal region and over the axon (CD9) which consists mainly of circular (ABD7). The innermost layer of the per- dense envelope around the node of Ranvier. The perineural endothelial cells myelin sheaths in CNS and PNS are il- possess a basal membrane at their per- lustrated in B. They represent a barrier its myelin sheath, the distance between the between nerve and surrounding tissue, sim- nodes of Ranvier, and the conduction ilarly to the endothelial cells of cerebral velocity of a nerve fiber. The mechanical cumference of an axon, the thicker the en- strength of the peripheral nerve is based on closing myelin sheath and the longer the in- its content of circular elastic fibers. When myelinated nerve fibers are nerves of the limbs, the perineurium is rein- still growing (e. The epineurium limbs), the internodes are growing in (CD11) borders on the perineurium; its length. The longer the internodes, the faster inner layers form concentric lamellae as the conduction velocity of the fiber. They change into loose connective tinguish between myelinated, poorly myeli- tissue containing fat cells (D12), blood ves- nated, and unmyelinated nerve fibers, also sels, and lymph vessels. Conductionvelocity is the slowest in the unmyelinatedCfibers (up to 2m/s); we are dealing here with a con- tinuous spread of excitation. By contrast, conduction in myelinated nerves is salta- tory, that is, it takes place in jumps. The morphological basis of saltatory conduction is the alternation of myelinated internodes and unmyelinated nodes of Ranvier; the current inside the axon jumps from one Kahle, Color Atlas of Human Anatomy, Vol. Myelin Sheath and Endoneural Sheath of Peripheral Nerves 41 2 PNS 6 7 CNS 5 B Node of Ranvier of a peripheral nerve fiber (top half) and of a cen- tral nerve fiber (bottom half) (according to Bunge) 3 2 7 6 1 4 10 A Peripheral nerve fiber, electron-microscopic diagram (according to Schröder) 13 7 8 9 11 14 C Peripheral nerve, cross section 9 11 12 12 D Detail of C Kahle, Color Atlas of Human Anatomy, Vol. In the gray matter, they and covering tissue of the CNS and has all the accompany neurons (satellitecells) (B). In the functions of connective tissue: support, white matter, they lie in rows between the metabolite exchange, and, in pathological nerve fibers (intrafascicular glia). They pro- processes, digestion of degenerating cells duce and maintain the myelin sheath (p. In response to three different types of neuroglia: astroglia tissue destruction, they phagocytose mate- (macroglia), oligodendroglia, and microglia rial (scavenger cells) and round up into (A). Astrocytes have a large, clear cell nucleus The frequently expressed view that micro- and numerous processes which give the cell gliawerenotderivedfromtheectodermbut a starlike appearance (A, C). There are proto- from the mesoderm (mesoglia) is not sup- plasmic astrocytes with few processes (usu- ported by evidence. The latter produce fibers and contain glial fila- ments in cell body and processes. Astrocytes are regarded as supporting el- ements, since they form a three-dimen- sional scaffold. On the outer surface of the brain, the scaffold thickens to form a dense fiber felt, the glial limiting membrane, which forms the outer limit of the ectodermal tissue against the mesenchymal meninges. Astrocytes extend processes to blood ves- sels and play a role in metabolite exchange (p.
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