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Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
Neuropharmacology: Acetylcholine & Alzheimer's
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Neuropharmacology: Acetylcholine & Alzheimer's

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Lecture 11 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University.

Lecture 11 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University.

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  • Transcript

    • 1. Neurochemistry III: Acetylcholine Brian J. Piper, Ph.D.
    • 2. Objectives• Synthesis• Breakdown• Receptors – nACh – M1 to M5• Neuroanatomy• Alzheimer’s Disease
    • 3. History1875-1968 • Sir Henry Dale (Dale’s law) describes 1873-1961 neuron communication as chemical involving Acectylcholine (ACh) in 1914 • Otto Loewi discovers ACh can inhibit the rate of heartbeat in frogs • Nobel Prize 1936
    • 4. 6.1 Synthesis of acetylcholine (ACh) by choline acetyltransferase • Choline: essential nutrient • Acetyl-CoA: acetyl co-enzyme A • ChAT: choline acetyl (COCH3) transferasehttp://lpi.oregonstate.edu/infocenter/othernuts/choline/
    • 5. Synthesis of acetylcholine (ACh) by choline acetyltransferase • Choline: essential nutrient • Acetyl-CoA: acetyl co-enzyme A • ChAT: choline acetyl (COCH3) transferasehttp://lpi.oregonstate.edu/infocenter/othernuts/choline/
    • 6. Choline During Development • Choline supplementation shows preclinical benefits against age related cognitive decline and against FAS. • Are there emotional benefits (open-field & FST) Glenn et al. (2012) Brain Research
    • 7. Acetylcholine Production • VAChT: vesicular Acetylcholine transporter packages ACh • Vesamicol: research drug that blocks VAChTStahl (2001). p. 468
    • 8. Acetylcholine Inactivation • AChE: acetylcholinesterase, breaks down Ach • ChT: Choline Transporter, recycles choline into presynaptic terminal Stahl (2001). p. 469.
    • 9. 6.9 Structure of the nicotinic ACh receptor• Ionotropic• Requires 2 ACh• Activated by nicotine• Blocked by curare
    • 10. 6.4 Myasthenia gravis, an autoimmune disorder Prevalence: 10/million Tx: AChE inhibitors, Upto 1:30: http://www.youtube.com/watch?v=XdpW5RMp-T0&feature=related
    • 11. Muscarinic Acetylcholine Receptors• Metabotropic• M1, M2, M3, M4, M5 Amanita muscaria• Trace amounts of muscarine isolated from Amanita muscaria in 1869• Found in brain & heart• Antagonist: Atropa Belladonna Inocybe rimosa (atropine)
    • 12. Preference?
    • 13. Preference?
    • 14. 6.7 Anatomy of cholinergic pathways in the brain• Nucleas basilis: connections to forebrain, important for cognition• Caudate-Putamen: important for motor function
    • 15. Lesson from Lesion Studies • 192 IgG-Saporin: destroys ACh neurons • Functional Deficits not shown until >70% depletions
    • 16. 6.6 Cholinergic synapses in the parasympathetic and sympathetic branches of the ANS
    • 17. Botulism• Infection causes reduced ACh and release• Infants are particularly susceptible
    • 18. Botulinum Toxin A• Botox is FDA approved for cosmetic purposes• Also used for excessive sweating
    • 19. Summary
    • 20. Aloysius ”Alois” Alzheimer• German psychiatrist• Described symptoms + pathology 1864-1913 – Neuronal loss – Plaques – Tangles• Presentation to SW German Psychiatrist meeting ignored but Emil KraeplinCipriani et al. (2011) Neurological Sciences, 32(2), 275-279. Auguste Deter, 1851-1906
    • 21. 1st, but possibly, atypical case
    • 22. Healthy Alzheimer’sDisease
    • 23. AD, external aspect
    • 24. AD, coronal cross section
    • 25. Amyloid Plaque• Amyloid Beta Peptide: 40/42 amino acids• Amyloid Plaque: clusters of Beta amyloid +• Neurofibrillary tangles
    • 26. Test of Neurocognitive Function • Mini-Mental Status Exam (MMSE) – Where are we in? – Count backwards by 7 starting with 100. – Remember 3 words. • Spatial Learning & Memory • Executive functionFolstein, Folstein, & McHugh (1975). J Psychiatric Research, 12, 189-198.
    • 27. Alzheimer’s Vaccine?• Immunization against AB42 produced antibodies• Brain versus BehaviorHolmes et al. (2008) Lancet, 372, 216-223.
    • 28. Executive Function Test: Trail Making Test: Part A
    • 29. Trail Making Test: Part B
    • 30. Executive Function Test 2: Tower of London
    • 31. Tower of London: Difficult Trial
    • 32. Genetic Risk Factors• Apolipoprotein E: Isoform 112 158 – Chromosome 19 E2 Cysteine Cysteine – 299 amino acids – E3 > E2 > E4 E3 Cysteine Arginine E4 Agrinine Agrinine
    • 33. ApoE & Alzheimer’s DiseaseCorder et al. (1993). Science, 261, 921-3.
    • 34. Hippocampus, CA1, tau IHCHigher magnification
    • 35. Current Alzheimer’s Treatments• Alzheimer’s does involve neurodegeneration of cholinergic neurons• Acetylcholinesterase inhibitors (tacrine) have resulted in only modest/brief benefits
    • 36. Summary AcetylcholineSynthetic EnzymesInactivating EnzymesVesicular TransporterMembrane TransporterWhere in brain (somas)?Ionotropic Receptor(s)Metabotropic Receptor(s)Agonist(s)Antagonist(s)Disease(s)
    • 37. Self-Test AcetylcholineSynthetic Enzymes Choline AcetyltransferaseInactivating Enzymes AcetylcholinesteraseVesicular Transporter VAChTMembrane Transporter Choline TransporterWhere in brain (somas)? Nucleus basilis, striatumIonotropic Receptor(s) nAChMetabotropic Receptor(s) M1 – M5Agonist(s) Nicotine, MuscarineAntagonist(s) AtropineDisease(s) Myasthenia Gravis, Alzheimer’s?

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