ABSTRACT
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease characterized by the accumulation of aggregated amyloid beta (Aß) and hyperphosphorylated tau along with a slow decline in cognitive functions. Unlike advanced AD, the initial steps of AD pathophysiology have been poorly investigated, partially due to limited availability of animal models focused on the early, plaque-free stages of the disease. The aim of this study was to evaluate the early behavioral, anatomical and molecular alterations in wild-type rats following intracerebroventricular injections of human Aß oligomers (AßOs). Bioactive human AD and nondemented control brain tissue extracts were characterized using ELISA and proteomics approaches. Following a bilateral infusion, rats underwent behavioral testing, including the elevated plus maze, social recognition test, Morris water maze and Y-maze within 6 weeks postinjection. An analysis of brain structure was performed with manganese-enhanced MRI. Collected brain tissues were analyzed using stereology, immunohistochemistry, ELISA and qPCR. No sensorimotor deficits affecting motor performance on different maze tasks were observed, nor was spatial memory disturbed in AD rats. In contrast, a significant impairment of social memory became evident at 21 days postinjection. This deficit was associated with a significantly decreased volume of the lateral entorhinal cortex and a tendency toward a decrease in the total brain volume. Significant increase of cleaved caspase-3-positive cells, microglial activation and proinflammatory responses accompanied by altered expression of synaptic markers were observed in the hippocampus of AD rats with immunohistochemical and qPCR approaches at 6 weeks postinjection. Our data suggest that the social memory impairment observed in AßO-injected rats might be determined by neuroinflammatory responses and synaptopathy. An infusion of native oligomeric Aß in the rat brain represents a feasible tool to model early plaque-free events associated with AD.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Disease Models, Animal , Hippocampus/metabolism , Humans , Maze Learning/physiology , Neurodegenerative Diseases/metabolism , Plaque, Amyloid/metabolism , RatsABSTRACT
The gray matter of the spinal cord is the seat of somata of various types of neurons devoted to the sensory and motor activities of the limbs and trunk as well as a part of the autonomic nervous system. The volume of the spinal gray matter is an indicator of the local neuronal processing, and this can decrease due to atrophy associated with degenerative diseases and injury. Nevertheless, the absolute volume of the human spinal cord has rarely been reported, if ever. Here, we use high-resolution magnetic resonance imaging, with a cross-sectional resolution of 50 × 50 µm and a voxel size of 0.0005 mm3 to estimate the total gray and white matter volume of a post mortem human female spinal cord. Segregation of gray and white matter was accomplished using deep learning image segmentation. Furthermore, we include data from a male spinal cord of a previously published study. The gray and white matter volumes were found to be 2.87 and 11.33 mL, respectively, for the female and 3.55 and 19.33 mL, respectively, for the male. The gray and white matter profiles along the vertebral axis were found to be strikingly similar, and the volumes of the cervical, thoracic, and lumbosacral sections were almost equal.NEW & NOTEWORTHY Here, we combine high-field MRI (9.4 T) and deep learning for a post mortem reconstruction of the gray and white matter in human spinal cords. We report a minuscule total gray matter volume of 2.87 mL for a female and 3.55 mL for a male. For comparison, these volumes correspond approximately to the distal digit of the little finger.
