16 research outputs found
Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopaty
The stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer’s disease. We recently identified a specific synaptic deficit of Nectin-3 in transgenic models for tauopathy. Here we defined cognitive impairment and electrophysiological problems in the SLM of Tau.P301L mice, which corroborated the structural defects in synapses and dendritic spines. Reduced diffusion of DiI from the ERC to the hippocampus indicated defective myelinated axonal pathways. Ultrastructurally, myelinated axons in the temporoammonic pathway (TA) that connects ERC to CA1 were damaged in Tau.P301L mice at young age. Unexpectedly, the myelin defects were even more severe in bigenic biGT mice that co-express GSK3β with Tau.P301L in neurons. Combined, our data demonstrate that neuronal expression of protein Tau profoundly affected the functional and structural organization of the entorhinal-hippocampal complex, in particular synapses and myelinated axons in the SLM. White matter pathology deserves further attention in patients suffering from tauopathy and Alzheimer’s disease
Investigation of cerebral autoregulation in the newborn piglet during anaesthesia and surgery
The relationship between cerebral autoregulation (CA) and the neurotoxic effects of anaesthesia with and without surgery is investigated. Newborn piglets were randomly assigned to receive either 6 h of anaesthesia (isoflurane) or the same with an additional hour of minor surgery. The effect of the spontaneous changes in mean arterial blood pressure (MABP) on the cerebral haemodynamics (oxy- and deoxy-haemoglobin, HbO2 and Hb) was measured using transverse broadband near-infrared spectroscopy (NIRS). A marker for impaired CA, concordance between MABP and intravascular oxygenation (HbD = HbO2 - Hb) in the ultra-low frequency domain (0.0018-0.0083 Hz), was assessed using coherence analysis. Presence of CA impairment was not significant but found to increase with surgical exacerbation. The impairment did not correlate with histological outcome (presence of cell death, apoptosis and microglial activation in the brain)
Effects on Hemostasis After Two-Year Use of Low Dose Combined Oral Contraceptives with Gestodene or Levonorgestrel
Generating an agricultural risk map based on limited ecological information: A case study using Sicyos angulatus
Wage Losses Due to Overqualification: The Role of Formal Degrees and Occupational Skills
TRAIL/DR5 Signaling Promotes Macrophage Foam Cell Formation by Modulating Scavenger Receptor Expression
Tauopathy Differentially Affects Cell Adhesion Molecules in Mouse Brain: Early Down-Regulation of Nectin-3 in Stratum Lacunosum Moleculare
Cell adhesion molecules are important structural substrates, required for synaptic plasticity and synaptogenesis. CAMs differ
widely in their expression throughout different brain regions and their specific structural and functional roles in the brain
remain to be elucidated. Here, we investigated selected cell adhesion molecules for alterations in expression levels and
neuronal localization in validated mouse models for Alzheimer’s disease that mimic the age-related progression of amyloid
accumulation and tauopathy. Among the cell adhesion molecules analyzed, Nectin-3 expression was affected most and
specifically in all mouse models with tauopathy. In particular was Nectin-3 depleted from the specific region of the
hippocampus, known as the stratum lacunosum and moleculare, in mice that express wild-type or mutant human protein
Tau, either chronically or sub-acutely. Tauopathy progresses from the entorhinal cortex to the hippocampus by unknown
mechanisms that could involve transport by the myelinated axons of the temporoammonic and perforant pathways. The
decreased expression of Nectin-3 in the stratum lacunosum moleculare is an early marker of impaired transport, and
eventual synaptic problems, caused by beginning tauopathy.peerReviewe