Diseases Affecting Sensation and Motor Control Nancy Long Sieber, Ph.D. September 20, 2010.

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Transcript of Diseases Affecting Sensation and Motor Control Nancy Long Sieber, Ph.D. September 20, 2010.

  • Diseases Affecting Sensation and Motor ControlNancy Long Sieber, Ph.D.September 20, 2010

  • Major Neurotransmitters

    Small MoleculesNeuropeptidesAcetylcholineNitric OxideBiogenic AminesEpinephrineNorepineprineDopamineSerotoninHistamineAmino AcidsGlutamateg-Aminobutyric Acid (GABA)GlycineAspartateHomocysteineTaurineNucleotidesAdenosineAdenosine triphosphateHypothalamic Releasing HormonesCorticotrophic Releasing HormoneGrowth Hormone Releasing HormoneThyrotrophin Releasing HormonePituitary Peptides endorphinsOxytoxinVasopressinAdrenocorticotropic Hormone (ACTH)Thyroid Stimulating Hormone (TSH)Growth HormoneGastrointestinal PeptidesSecretinSubstance PInsulinGastrinNeurotensinSomatostatinCholecystokininOthersAngiotensinBradykininNeuropeptide YCalcitonin

  • Sensory neurons can diverge (a) or converge (b) as they ascend towards the brain

  • The body is mapped onto the somatosensory cortex.

  • Lower Motor Neurons(from spinal cord to muscle) =>UpperMotor Neurons (all motor neurons withinthe CNS) =>

  • http://www.riversideonline.com/source/images/image_popup/ww5r308_big.jpgMS is characterized by demyelinization of neurons in the CNS

  • Disease of Sensory and/or Motor ControlParkinsons Disease results from death of dopamine-containing neurons in the substantia nigra. Affects ability to initiate movements.

    Multiple Sclerosis affects neurons in the CNS involved in sensation and movement. Some also experience mild cognitive effects.

    Amyotrophic Lateral Sclerosis affects motor neurons both in the CNS and in the periphery.

  • Parkinsons DiseaseSubstantia nigra cells in the basal ganglia are gradually killed off, but the mechanism of neuronal death is not knownThese cells normally synapse on cells involved in the initiation of movement. Patient experiences intention tremor, and rigidity. Movements become increasingly difficult to carry out.The disease shortens life expectancy. Patients become increasingly frail and immobilized. Some have trouble with swallowing.

  • Regions of the brain affected by Parkinsons Diseasehttp://www.newhopeforparkinsons.com/images/brainillustration2.gif

  • Multiple SclerosisAn autoimmune disease that leads to demyelinization of neurons in the CNSPatients usually present with blurred or double vision. They go on to experience abnormal sensations, and muscle weakness. 50% of patients need help with walking within 15 years of diagnosis.

  • Pathogenesis of MSIn patients with MS, T lymphocytes, which are normally excluded from the brain by the blood-brain barrier (BBB) are able to enter.

    These cells are thought to trigger the damage to myelinated neurons in the CNS.

    The cause of this opening of the BBB is unknown it the cause of the problem, or is it just a consequence of inflammation caused by something else?

  • Blood vessels in the human brainZlokovic & Apuzzo: Neurosurgery 43(4):877-878, 1998

  • http://sofija.files.wordpress.com/2007/01/ms_worldmap.jpg

  • Many factors are thought to contribute to MS:

    Intrinsic problems with immune system - probably common to all autoimmune diseases, probably genetic.

    Problems with the blood-brain barrier, allowing T cells to enter the CNS and promote production of antibodies against myelin

    A specific Infectious agent Some have proposed that a virus triggers the autoimmune response that leads to demyelinization. No specific agent has been found

    Vitamin D deficiency the geographic distribution supports this. Vitamin D is involved in regulating the immune system, as well as neural function.

  • Proposed scheme for virus-mediated autoimmunity in multiple sclerosis.

    Grigoriadis and Hadjigeorgiou Journal of Autoimmune Diseases 2006 3:1 doi:10.1186/1740-2557-3-1

  • http://content.revolutionhealth.com/contentimages/h9991221.jpgMRI Images help diagnose and monitor MS

  • Treatments for MSAnti-inflammatory agents corticosteroids, chemotherapeutic agents, etc. as used to treat lupus. Drawbacks: These drugs have many side effects. In addition, they generally increase the risk of infection, and viral and bacterial infections have been shown to speed the progression of MS.

    Supplemental vitamin D has been shown to slow the progression of MS

    Tysabri A monoclonal antibody against T cells, which blocks their entry into the CNS. Drawback: cripples brain defenses against infection. Patients are at risk of deadly brain infections, especially progressive multifocal leukoencephalopathy (PML).

  • ALS affects both upper (within the CNS) and lower (those that directly innervate muscle) motor neurons.http://len.epfl.ch/webdav/site/len/shared/import/migration/ALS1.jpg

  • Genetics and ALS5-10% of cases are strictly genetic (Familial ALS).

    Of these about 20% are due to a defect in an enzyme called superoxide dismutase 1 (SOD1), which scavenges free radicals.

    This finding has led some to speculate that free radical damage may be involved in other forms of the disease.

    The defective protein may also interfere with movement of ADP into mitochondria, interfering with ATP production.

  • Possible environmental risk factorsExposure to a dietary toxin called BMAA may account for high incidence in Guam and other places in the western Pacific.

    US military veterans from both the Pacific and the Gulf War.

    Exposure to herbicides has long been suspected, as clusters have been seen in athletes and farmers.

  • Possible Mechanisms of ALS PathogenesisOxidant injury, perhaps due to some abnormality in antioxidant systemsGlutamate toxicity, perhaps due to a defect in astroglial cells which normally remove this neurotransmitter from the synapse. The resulting excitotoxicity leads to neuronal death, causing further release of glutamate.

  • Treatments for ALSRiluzole, a drug that decreases glutamate release is the only FDA-approved drug for ALS. It is only moderately effective suggesting that other mechanisms are involved in the pathogenesis of ALS.Other drugs are used to treat symptoms of the disease, including muscle cramps, spasms, fatigue, etc.