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Neuroimaging Of The Philadelphia Neurodevelopmental Cohort, Theodore D. Satterthwaite, Mark A. Elliott, Kosha Ruparel, James Loughead, Karthik Prabhakaran, Monica E. Calkins, Ryan Hopson, Chad Jackson, Jack Keefe, Marisa Riley, Frank D. Mentch, Patrick Sleiman, Ragini Verma, Christos Davatzikos, Hakon Hakonarson, Ruben C. Gur, Raquel E. Gur

Public Health Resources

The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8–21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, …

Deficiency Of Tnf Receptors Suppresses Microglial Activation And Alters The Susceptibility Of Brain Regions To Mptp-Induced Neurotoxicity: Role Of Tnf-Α, Krishnan Sriram, Joanna M. Matheson, Stanley A. Benkovic, Diane B. Miller, Michael I. Luster, James P. O'Callaghan

Public Health Resources

Enhanced expression of tumor necrosis

factor (TNF) -α, is associated with the neuropathological

effects underlying disease-, trauma- and chemically

induced neurodegeneration. Previously, we have shown

that deficiency of TNF receptors protects against

MPTP-induced striatal dopaminergic neurotoxicity,

findings suggestive of a role for TNF-α in neurodegeneration.

Here, we demonstrate that deficiency of TNF

receptors suppresses microglial activation and alters

the susceptibility of brain regions to MPTP. MPTPinduced

expression of microglia-derived factors,

TNF-α, MCP-1, and IL-1α, preceded the degeneration

of striatal dopaminergic nerve terminals and astrogliosis,

as assessed by loss of striatal dopamine and TH, …

Mice Deficient In Tnf Receptors Are Protected Against Dopaminergic Neurotoxicity: Implications For Parkinson’S Disease, Krishnan Sriram, Joanna M. Matheson, Stanley A. Benkovic, Diane B. Miller, Michael I. Luster, James P. O’Callaghan

Public Health Resources

The pathogenic mechanisms underlying idiopathic Parkinson’s disease (PD) remain enigmatic. Recent findings suggest that inflammatory processes are associated with several neurodegenerative disorders, including PD. Enhanced expression of the proinflammatory cytokine, tumor necrosis factor (TNF)-α, has been found in association with glial cells in the substantia nigra of patients with PD. To determine the potential role for TNF-α in PD, we examined the effects of the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), a dopaminergic neurotoxin that mimics some of the key features associated with PD, using transgenic mice lacking TNF receptors. Administration of MPTP to wild-type (+/+) mice resulted in a time-dependent expression of TNF-α …