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Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accumulate NF-L to approximately 4-fold the(More)
Hereditary canine spinal muscular atrophy (HCSMA) is an autosomally dominant disease of motor neurons that shares many pathological features with human motor neuron disease. A particularly striking feature of the affected, accelerated phenotype (homozygous HCSMA) is that profound weakness develops before appreciable motor neuron cell death occurs (Cork et(More)
Age-associated changes in cholinergic, monoaminergic and amino acid neurotransmitter systems were analyzed in 14 brain regions of 23 rhesus monkeys that ranged in age from 2 to 37 years. In the frontal pole, the levels of choline acetyltransferase (ChAT) activity, the density of [3H]ketanserin (serotonin type-2) binding sites and endogenous levels of(More)
The formation of clusters of altered axons and dendrites surrounding extracellular deposits of amyloid filaments (neuritic plaques) is a major feature of the human brain in both aging and Alzheimer's disease. A panel of antibodies against amyloid filaments and their constituent proteins from humans with Alzheimer's disease cross-reacted with neuritic plaque(More)
Rhesus monkeys (Macaca mulatta) reared during the first year of life without social contact develop persistent stereotyped movements, self-directed behaviors, and psychosocial abnormalities, but neurobiological mechanisms underlying the behaviors of socially deprived (SD) monkeys are unknown. Monkeys were reared in total social deprivation for the first 9(More)
In aged human beings and in individuals with age-associated degenerative disorders, particularly Alzheimer's disease (AD), neurons develop cytoskeletal abnormalities, including neurofibrillary tangles (NFT) and senile plaques (SP). Senile plaques occur in several nonhuman species; however, NFT, with ultrastructural or immunocytochemical similarities to(More)
The authors counted axons in one optic nerve from each of 28 juvenile and aged rhesus monkeys using an automated image analysis system. All nerves were fixed immediately after death and treated identically. Animals ranged in age from 1 1/2 to 29 yr, which correlates with a human age range of 4 1/2-87 yr. Mean axonal number for all specimens was 1,117,859.(More)
Transgenic mice containing the early region of human papovavirus JC were produced. Some of these mice exhibited a shaking disorder similar to the previously described mutant mice jimpy or quaking. Neuropathological analysis indicated a dysmyelination in the central nervous system, but not the peripheral nervous system. A high level of JCV T-antigen mRNA was(More)
Hereditary canine spinal muscular atrophy (HCSMA) features rapidly progressive muscle weakness that affects muscles in an apparent proximal-to-distal gradient. In the medial gastrocnemius (MG) muscle of homozygous HCSMA animals, motor unit tetanic failure is apparent before the appearance of muscle weakness and appears to be presynaptic in origin. We(More)
Hereditary canine spinal muscular atrophy (HCSMA), a dominantly inherited disorder of motor neurons, has three phenotypes: accelerated, intermediate, and chronic. In the accelerated and intermediate phenotypes, axonal sizes in ventral roots were smaller than in controls. Reductions in axonal size occurred primarily in large axons, and the frequency of(More)