Morphological and functional alterations in pyramidal cells in schizophrenic prefrontal cortex.
Item
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Title
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Morphological and functional alterations in pyramidal cells in schizophrenic prefrontal cortex.
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Identifier
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AAI3231955
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identifier
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3231955
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Creator
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Broadbelt, Kevin.
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Contributor
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Adviser: Liesl Jones
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Date
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2006
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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Schizophrenia, a disease of the brain, is one of the most debilitating mental illnesses known. Studies suggest morphological and functional alterations of pyramidal cells in the prefrontal cortex (PFC). Two regions of the PFC implicated in schizophrenia are Area's 9 and 32. Examination of Area 32 in 11 schizophrenics and 11 comparison subjects using Golgi-stained material showed a decrease in primary (33%) and secondary (29%) basilar dendrites on pyramidal neurons in layer V. Layer III showed a decrease in primary (17.4%) and secondary (15%) basilar dendrites also. Area 9 of the dorsolateral PFC exhibited a similar trend. A decrease in primary (23%) and secondary (23%) basilar dendrites in layer III were seen. In layer V a decrease in primary (29%) and (31%) secondary basilar dendrites was seen. A decrease in synaptic spine number on primary (18%) and secondary (19%) basilar dendrites in layer III were also seen. Layer V exhibited a decrease in synaptic spines on primary (17%) and secondary (18%) basilar dendrites. Using Scholl analysis, basilar dendritic trees in Area 32 were less extensive in the schizophrenia group.;Neurogranin immunostaining was reduced in layers III (70%) and V (50%) in area 9 using Area Fraction Analysis. Area 32 exhibited (36%) reduction in layer III and a (40%) reduction in layer V. There was no difference in either layer in density of positively stained pyramidal cells. A schizophrenia-associated decrease in Calmodulin area fraction in Areas 9 and 32 was seen. Area 9 (58%) reduction in layer III and (44%) reduction in layer V. Area 32 (51%) reduction in layer III and (32%) reduction in laver V.;A decrease in Neurogranin could allow more Calmodulin to interact with free calcium and activate the Calcium-calmodulin signal transduction pathway inappropriately. Activating this pathway incorrectly could, alter information processing of the pyramidal cell. Neurogranin and Calmodulin are greatly reduced in the same neuron population as the loss of dendrites. This data suggests that calcium signaling is altered in prefrontal cortical areas 9 and 32 in schizophrenia and these alterations could lead to loss of dendrites, altered signaling and aberrant information processing.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
