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Bioluminescence imaging in transgenic mice expressing firefly luciferase in Doublecortin+ (Dcx) neuroblasts might serve as a powerful tool to study the role of neurogenesis in models of brain injury and neurodegeneration using non-invasive, longitudinal in vivo imaging. Therefore, we aimed to use BLI in B6(Cg)-Tyrc-2J/J Dcx-Luc (Doublecortin-Luciferase, Dcx-Luc) mice to investigate its suitability to assess neurogenesis in a unilateral injection model of Parkinson's disease. We further aimed to assess the blood brain barrier leakage associated with the intranigral 6- OHDA injection to evaluate its impact on substrate delivery and bioluminescence signal intensity. Two weeks after lesion, we observed an increase in bioluminescence signal in the ipsilateral hippocampal region in both, 6- OHDA and vehicle injected Dcx-Luc mice. At the same time, no corresponding increase in Dcx+ neuroblast numbers could be observed in the dentate gyrus of C57Bl6 mice. Blood brain barrier leakage was observed in the hippocampal region and in the degenerating substantia nigra of C57Bl6 mice in vivo using T1 weighted Magnetic Resonance Imaging with Gadovist® and ex vivo using Evans Blue Fluorescence Reflectance Imaging and mouse Immunoglobulin G staining. Our data suggests a BLI signal dependency on blood brain barrier permeability, underlining a major pitfall of substrate/tracer dependent imaging in invasive disease models. [ABSTRACT FROM AUTHOR]

Research into the development of Alzheimer's disease (AD) provides increasing evidence that vascular risk factors, including high serum cholesterol, might influence the progression of cognitive impairment and neural degeneration. In this study, we investigated the effects of high dietary cholesterol intake and the cholesterol-lowering liver X receptor-agonist T0901317 on capillary density, amyloid-β deposition, and presynaptic boutons in the hippocampus of adult (8 months) and aged (15 months) AβPPswe-PS1dE9 and wild-type mice to elucidate how cholesterol may affect neurodegenerative processes in aging and AD. Our results show increased number of presynaptic boutons in 15-month-old AβPP-PS1 mice compared to age-matched wild-type animals, but no difference at 8 months of age. High cholesterol intake accelerated this response by increasing the amount of presynaptic boutons at 8 and 15 months of age, while T0901317 intake decreased the amount of presynaptic boutons in 15-month-old AβPP-PS1 mice. These findings suggest a synaptic compensatory response to maintain connectivity during aging. We hypothesize that high cholesterol intake may cause impaired cerebral blood flow inducing ischemia, fortifying the above mentioned hypothesis of a compensatory mechanism. Contrarily, cholesterol-lowering agents may positively influence cerebral circulation, thereby diminishing aggravation of AD-like pathology. [ABSTRACT FROM AUTHOR]