Nerve tissue, neurotransmitters, blood-brain barrier, ALS/Lou Gehrig's, myasthenia gravis/rag doll syndrome, multiple sclerosis, neurofibromatosis, organs, types/modes of glandular secretion, cellular communication

9 Pages
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Department
Biomedical Science
Course Code
BMS 460
Professor
D.Rao Veeramachaneni

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Description
11 September Nerve Tissue Three types of neurons Sensory/Afferent From all parts of body to CNS Motor/Efferent From CNS to muscle and epithelial glands Interneurons/connecting neurons Interneurons are neither motor nor sensory. The term is also applied to brain and spinal cord neurons whose axons connect only with nearby neurons, to distinguish them from “projection” neurons, whose axons (projection fibers) project to more distant regions of brain or spinal cord. Two major mechanisms Ionotropic = stimulus-gated ion channels Metabotropic = G-protein complexes Neurotransmitters Acetylcholine: Cholinergic transmission Simple molecule neurotransmitter Acetylcholine (Ach) is used by all motor axons, autonomic preganglionic neurons, and postganglionic parasympathetic nerves and by some cells of the motor cortex and basal ganglia. Ach also functions extensively in the brain to maintain cognitive function. Depending on the postsynaptic receptor, Ach can be either stimulatory (e.g., at the neuromuscular junction by motor neurons) or inhibitory (e.g., in parasympathetic postganglionic fibers to cardiac muscle) Pathophysiology of cholinergic transmission: myasthenia gravis, Parkinson disease, Alzheimer dementia Amino acids Simple molecule neurotransmitter Glutamate: glutamatergic transmission; glutamate is the primary stimulatory neurotransmitter of the brain Gamma aminobutyric acid (GABA); GABA is the primary inhibitory neurotransmitter in the brain Pathophysiology: Huntington disease Glycine; glycine is the primary inhibitory neurotransmitter of the spinal cord Pathophysiology: Tetanus toxicity Monoamines Simple molecule neurotransmitters These neurotransmitters contain a single amine group in their chemical structure and include norepinephrine, serotonin, and dopamine. Pathophysiology: Depression Neuropeptides Exclusively metabotropic Neuropeptides alter gene expression → longer duration of action E.g., Substance P, neuropeptide Y, enkephalins, endorphins, and nitric oxide Neuropeptides may be secreted at the same time as a small-molecule neurotransmitter such as norepinephrine (co-transmission). This results in an immediate, rapid response (because of the smaller neurotransmitter) and a delayed but prolonged response caused by the neuropeptide. E.g., glutamate and substance P are co-transmitted in the pain pathway; glutamate causes immediate inhibition of pain neurotransmission whereas substance P causes changes in gene expression to produce a lasting effect. Pathophysiology: Clinical examples Huntington disease: There is progressive deterioration of the caudate nucleus, putamen, and frontal cortex, but clinical symptoms do not appear until the fourth or fifth decade, by which time many patients have already passed on the mutated autosomal dominant gene to their children. Deterioration starts with hypertonicity, incontinence, anorexia, dementia, and death. Loss of GABA- secreting neurons between the striatum and globus pallidus is one of the factors responsible for the abnormal movements. Tetanus: Glycine secretion in the spinal cord is inhibited by the tetanus toxin, exposure to which results in excessive stimulation (dis-inhibition) of the lower motor neurons, producing spastic muscle contraction (i.e., spastic paralysis). Nerves must sprout new terminals before the patient can regain normal function. Depression: The monoamine deficiency theory links depression to a deficiency in at least one of the three monoamine neurotransmitters: norepinephrine, serotonin, and dopamine. Extensive pharmacologic support for this theory has been obtained over the years, as evidenced by the efficacy of monoamine oxidase inhibitors and tricyclic antidepressants, which increase levels of monoamine neurotransmitters in brain. However, these drugs affect levels of other neurotransmitters and have numerous side effects. More recently, serotonin-specific reuptake inhibitors (SSRIs) and non-serotonin-specific reuptake inhibitors (NSRIs) have been shown to be extremely effective in the treatment of depression with minimal side effects. Nerve Tissue Cellular Components Two types of cells Neurons/nerve cells Transmit/conduct impulses Neuroglia/glial cells Connective tissue cells that support neurons Several functions Myelin production: oligodendrocytes in CNS; Schwann cells in PNS Blood-brain barrier: astrocytes Phagocytosis: microglia Neurons secrete exosomes which may influence synaptic plasticity. Microglia modulate neurotransmission via shedding microvesicles. Astrocyte-derived exosomes carry neuroprotective cargo and could contribute to neuronal survival Neuronal signals trigger exosome release from oligodendrocytes by raising intracellular 2+ Ca -levels. Upon internalization by neurons these exosomes could provide support to axons. Microglia take up and degrade oligodendroglial exosomes without changing their inflammatory properties. Under specific pathological conditions these exosomes may transfer antigens to microglial cells or other APCs and induce inflammatory responses Nucleus, ganglion and nerve bundle Nucleus – collection of neuronal cell bodies in CNS Sexually dimorphic nucleus – appears different in different sexes Nerve bundle – collection of axons Ganglia – collection of neuronal cell bodies in PNS Blood-Brain Barrier The blood-brain (CNS) barrier is a separation of circulating blood from the brain extracellular fluid in the CNS. It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. This barrier also includes a thick basement membrane of capillary endothelium and astrocytic endfeet. Endothelial cells restrict the diffusion of microscopic objects (e.g., bacteria) and large or hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of small hydrophobic molecules (O , 2O , h2rmones). Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins. Clinical Implications L-DOPA (Levodopa) crosses blood-brain barrier, whereas dopamine itself cannot. Thus, L-DOPA is used to increase dopamine concentrations in the treatment of Parkinson’s disease and dopamine-responsive dystonia. Once L-DOPA has entered the CNS, it is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase (DOC). Besides the CNS, L-DOPA is also converted into dopamine from within the peripheral nervous system. The resulting hyperdopaminergia causes many of the adverse side effects seen with sole L-DOPA administration. To bypass these effects, it is standard clinical practice to co-administer (with L-DOPA) a peripheral DOPA decarboxylase inhibitor (DOCI) to prevent the peripheral synthesis of dopamine from L-DOPA. L-DOPA (L-3,4-dihydroxyphenylalanie) is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines. L-DOPA can be manufactured and in its pure form is sold as a psychoactive drug. As a drug it is used in the clinical treatment of Parkinson’s disease and dopamine-related dystonia. Simple in concept, but challenging to make a therapeutic reality! Neurons derived from cord-blood cells may represent new therapeutic option Schwann cells that form myelin sheaths in PNS have an outer cell membrane called neurilemma, which plays an essential part in regeneration of cut and injured axons. Axons in the brain and spinal cord have no neurilemma and, therefore, the potential regeneration in the brain and spinal cord is far less than it is in the PNS. Grafting on a cure – in rats, cells from the peripheral nervous system
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