MRI Research Today is a free monthly online journal that collates and summarizes the latest research about MRI, including details on magnetic resonance imaging, neuroimaging, brain tumors. | ||||||||
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In vivo MRI identifies cholinergic circuitry deficits in a Down syndrome model.Chen Y, Dyakin VV, Branch CA, Ardekani B, Yang D, Guilfoyle DN, Peterson J, Peterhoff C, Ginsberg SD, Cataldo AM, Nixon RA Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, United States; Center for Advanced Brain Imaging, Nathan Kline Institute, Orangeburg, NY, United States. In vivo quantitative magnetic resonance imaging (MRI) was employed to detect brain pathology and map its distribution within control, disomic mice (2N) and in Ts65Dn and Ts1Cje trisomy mice with features of human Down syndrome (DS). In Ts65Dn, but not Ts1Cje mice, transverse proton spin-spin (T(2)) relaxation time was selectively reduced in the medial septal nucleus (MSN) and in brain regions that receive cholinergic innervation from the MSN, including the hippocampus, cingulate cortex, and retrosplenial cortex. Basal forebrain cholinergic neurons (BFCNs) in the MSN, identified by choline acetyltransferase (ChAT) and nerve growth factor receptors p75(NTR) and TrkA immunolabeling were reduced in Ts65Dn brains and in situ acetylcholinesterase (AChE) activity was depleted distally along projecting cholinergic fibers, and selectively on pre- and postsynaptic profiles in these target areas. T(2) effects were negligible in Ts1Cje mice that are diploid for App and lack BFCN neuropathology, consistent with the suspected relationship of this pathology to increased App dosage. These results establish the utility of quantitative MRI in vivo for identifying Alzheimer's disease-relevant cholinergic changes in animal models of DS and characterizing the selective vulnerability of cholinergic neuron subpopulations. Published 8 January 2008 in Neurobiol Aging.
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