Early mediodorsal thalamic damage induces alterations in prefrontal cortex: Potential model for schizophrenia.
Item
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Title
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Early mediodorsal thalamic damage induces alterations in prefrontal cortex: Potential model for schizophrenia.
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Identifier
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AAI3296965
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identifier
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3296965
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Creator
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Marmolejo, Naydu.
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Contributor
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Adviser: Liesl B. Jones
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Date
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2008
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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 | Biology, Anatomy
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Abstract
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One of the most consistent findings in schizophrenia is a decrease in volume and neuronal number in the medial dorsal nucleus of the thalamus (MD) (Pakkenberg 1990; Pakkenberg 1992; Popken et al., 2000; Young et al., 2000; Byne et al., 2001; Lewis et al., 2001; Byne et al., 2002). The MD is reciprocally connected to the prefrontal cortex (PFC), another region implicated in schizophrenia. Focusing on the interplay between the MD and the PFC, this study examined the hypothesis that early damage to the MD may lead to alterations in morphology of pyramidal cells in the PFC, similar to that observed in schizophrenics. Unilateral electrolytic lesions of the MD in Long-Evans rat pups were made on postnatal day 4 (P4) and animals developed to P60. We examined morphological profiles for pyramidal cells in three subregions of the PFC: prelimbic (PL), anterior cingulate 1(CG-1), and Dorsolateral anterior cingulate (DL) cortices, which receive afferents from the MD. Structural alterations were assessed by three meausures: immunostaining levels for microtubule-associated protein 2, an indicator of dendritic integrity (Caceres et al., 1992), number of basilar dendrites, as well as spine density. Lesions causing mean MD volume decreases of 12.30% led to significant decreases in MAP2 immunostaining. No difference was observed in pyramidal cell density in any of the regions in or layers, so the reduction in MAP2 staining likely occurred as a function of reduced protein levels and not due to lower cell densities in these regions. Early postnatal thalamic lesions led to significant reductions in the number of primary and secondary dendrites for pyramidal cells in the PFC, suggesting early MD damage affected the dendritic arbors. Spines on pyramidal dendrites are the predominant targets of the MD (Kuroda et al., 1995), and are induced by afferent input activity (Kossel et al., 1997). Mean nuclear volume decreases of 14.82% in the MD led to decreases in the density of spines along basilar dendrites. The data showed that early loss of cells in the MD could affect the morphology of pyramidal neurons in the PFC, and support the hypothesis that the alterations in PFC observed in schizophrenic subjects could arise as a consequence of early MD damage.
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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.
