Publications by authors named "Mark S Szczypka"

Results obtained in recent experiments suggest that bone marrow-derived cells (BMDCs) engraft into tissues and differentiate into various somatic cell types. However, it is unclear whether injury is required for the phenomenon to occur at appreciable frequencies. In this study we tested whether BMDCs engraft into kidneys and differentiate into renal cells in the absence or presence of toxic injury.

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Dopamine-deficient (DD) mice become hypophagic and die of starvation by 3 to 4 weeks of age unless dopamine is restored by daily treatment with l-3-4-dihydroxyphenylalanine (l-dopa). We demonstrate here that DD mice mount qualitatively normal counter-regulatory blood glucose responses to insulin and 2-deoxy-d-glucose (2-DG). However, unlike control mice, DD mice fail to eat in response to acute glucoprivation induced by insulin or 2-DG.

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The neuropeptide neurotensin (NT) is highly sensitive to changes in dopaminergic signaling in the striatum, and is thought to modulate dopamine-mediated behaviors. To explore the interaction of NT with the dopamine system, we utilized mice with a targeted deletion of dopamine synthesis specifically in dopaminergic neurons. Dopamine levels in dopamine-deficient (DD) mice are less than 1% of control mice, and they require daily administration of the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) for survival.

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Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders.

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Administration of amphetamine to mice evokes hyperlocomotion. Dopamine deficient (DD) mice, in which tyrosine hydroxylase (TH) has been specifically inactivated in dopaminergic neurons, have a blunted response to amphetamine, indicating that the hyperlocomotive response requires dopamine. Dopamine production can be restored to specific brain regions by using adeno-associated viruses expressing TH and GTP cyclohydrolase 1 (GTPCH1).

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Depletion of dopamine in adult rats by treatment with the neurotoxin 6-hydroxydopamine (6-OHDA) causes severe deficits in feeding, drinking, and movement that often lead to death. However, when neonatal rats are treated similarly, they survive normally, suggesting that compensatory adaptation to dopamine depletion occurs. In contrast, dopamine-deficient mice that have a selective genetic deficiency in dopamine production die 2-4 weeks after birth.

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