Neural oscillations during cognitive processes in an App knock-in mouse model of Alzheimer's disease pathology.

Multiple animal models have been created to gain insight into Alzheimer's disease (AD) pathology. Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid ß plaques, one of the pathological hallmarks observed in AD patients. However, recent evidence suggests that the overexpression of APP by itself can confound some of the reported observations. Therefore, we investigated in the present study the AppNL-G-Fmodel, an App knock-in (App-KI) mouse model that develops amyloidosis in the absence of APP-overexpression. Our findings at the behavioral, electrophysiological, and histopathological level confirmed an age-dependent increase in Aß1-42 levels and plaque deposition in these mice in accordance with previous reports. This had apparently no consequences on cognitive performance in a visual discrimination (VD) task, which was largely unaffected in AppNL-G-F mice at the ages tested. Additionally, we investigated neurophysiological functioning of several brain areas by phase-amplitude coupling (PAC) analysis, a measure associated with adequate cognitive functioning, during the VD task (starting at 4.5 months) and the exploration of home environment (at 5 and 8 months of age). While we did not detect age-dependent changes in PAC during home environment exploration for both the wild-type and the AppNL-G-F mice, we did observe subtle changes in PAC in the wild-type mice that were not present in the AppNL-G-F mice.

Feasibility of in utero telemetric fetal ECG monitoring in a lamb model.

OBJECTIVES: If fetal ECG (fECG) devices could be miniaturized sufficiently, one could consider their implantation at the time of fetal surgery to allow permanent monitoring of the fetus and timely intervention in the viable period. We set up an experiment to evaluate the feasibility of in utero direct fECG monitoring and telemetric transmission using a small implantable device in a lamb model. METHODS: A 2-lead miniature ECG sensor (volume 1.9 cm(3); weight 3.9 g) was subcutaneously implanted in 2 fetal lambs at 122 days gestation (range 119-125; term 145 days). The ECG sensor can continuously register and transmit fECG. The signal is captured by an external receiving antenna taped to the maternal abdominal wall. We developed dedicated software running on a commercial laptop for on-line analysis of the transmitted fECG signal. This was a noninterventional study, i.e. daily readings of the fECG signal were done without clinical consequences to the observations. RESULTS: fECG could be successfully registered, transmitted by telemetry and analyzed from the moment of implantation till term birth in one case (24 days). In the second case, unexplained in utero fetal death occurred 12 days after implantation. In this subject, agonal fECG changes were recorded. CONCLUSION: An implanted miniature (<2 ml) ECG sensor can be used to retrieve, process and transmit continuously a qualitative fECG signal in third-trimester fetal lambs. The telemetric signal could be picked up by an external antenna located within a 20-cm range. In this experiment, this was achieved through taping the external receiver to the maternal abdomen. Any acquired signal could be transmitted to a commercially available laptop that could perform on-line analysis of the signal.

Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms.

The murine VEGF gene is alternatively transcribed to yield the VEGF(120), VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF(120/120) mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF(164), was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.