Lecture+14+Neurochemistry - Changes in Neurochemistry with...

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1 Changes in Neurochemistry with Aging Neurotransmitter systems Dopamine Acetylcholine Serotonin Blood flow and metabolism Cortical Projections of Key Systems Basal Forebrain Cerebral Cortex Raphe Nucleus Cerebral Cortex Locus Ceruleus Cerebral Cortex Acetylcholine Serotonin Norepinephrine Substantia Nigra Limbic and Frontal Cortex Dopamine Ventral Tegmentum Caudate/ Putamen nigrostriatal mesolimbic mesocortical
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2 Measuring Neurochemistry in Aging 3 methods: postmortem, PET, spinal fluid Postmortem: Generally requires rapid brain removal (in situ metabolism of neurotransmitters) PET: Quantitative methods possible, must take brain atrophy into account Spinal fluid: usually limited to metabolites of neurotransmitters Basal Forebrain Cholinergic System
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3 Acetylcholine Synthesis Action potential Acetylcholine synthethic enzyme: Choline Acetyl-transferase (ChAT) Acetylcholine degredation: Acetylcholinesterase (AChE) Measurement of Cholinergic Neurochemistry can use Vesamicol, ChAT or AChE . AChE is associated with neurons that receive cholinergic innervation (cholinoceptive) but not necessarily that use acetylcholine as a neurotransmitter so it is not as good a marker of cholinergic neurons Transport into vesicles via vesicular transporter - can be labelled with vesamicol Scopolamine effects on delayed memory in primates Scopolamine is a muscarinic cholinergic antagonist It has anti- cholinergic effects
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4 Scopolamine has similar effects in aged people Acetylcholine and Cognition Physostigmine (a cholinergic agonist) improves memory performance in old monkeys Anticholinergic drugs - scopolamine - induce transient amnesia in normal humans More recent data suggest that this effect is not specific for episodic memory - also attention, working memory frontal lobe function Controversial evidence for decreased cholinergic function in aging, more evidence for reduction in Alzheimer’s disease
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5 Mesolimbic and Mesocortical Dopamine Pathways Neuron Loss shows regional variability: Neurons are lost in the substantia nigra with age at a rate of 5-8%/decade This results in changes in the brain dopamine system with age
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Lecture+14+Neurochemistry - Changes in Neurochemistry with...

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