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Biomedical subjects

R G Struble

Publications and source records attributed to R G Struble.

7 recordsLinked to original sources

Distribution of amyloid in the brainstem of patients with Alzheimer disease.

A4 protein (beta-protein, beta-amyloid) deposits were identified with silver stains in postmortem brainstem sections from 13 patients with Alzheimer disease (AD), 6 patients with mixed Alzheimer disease and Parkinson disease (AD-PD), 5 disease controls, and 2 elderly controls. A rostro-caudal gradient of A4 was found in patients with AD and AD-PD, such that A4 was most prevalent in the midbrain and least prevalent in the medulla. The brainstem of the controls contained little or no A4. The midbrain tectum and tegmentum contained the greatest densities of A4, but the red nucleus and substantia nigra pars reticulata were largely spared. This distribution of A4 suggests that A4 deposition is a function of synaptic connectivity rather than passive diffusion from vascular sources.

Adult

Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques.

To assess the contributions of the basal forebrain cholinergic nuclei to visual recognition memory in macaques, we compared the effects of lesions of (a) the nucleus basalis of Meynert, (b) the medial septal and diagonal band nuclei, and (c) all nuclei combined on performance of delayed nonmatching-to-sample with trial-unique stimuli. Whereas monkeys with the separate lesions did not differ from each other or from normal control animals, those with combined lesions showed a significant impairment. With time and extended practice, however, the performance of the animals with combined lesions recovered to normal levels. During the recovery period, these monkeys showed an initially increased sensitivity to scopolamine that later dissipated, at which time they also failed to show the improvement that follows physostigmine administration in normal animals. Postmortem assessment of cortical choline acetyltransferase activity revealed that only the group with combined lesions had significant depletion of this enzyme. The results suggest that (1) the basal forebrain cholinergic system participates in mnemonic processes in primates and that (2) extensive damage to this system is necessary before impairments in recognition memory, even transient ones, can be observed.

Acetylcholinesterase

Muscarinic cholinoceptive neurons in the frontal cortex in Alzheimer's disease.

The cellular distribution of muscarinic acetylcholine receptor protein in the frontal cortex of Alzheimer (AD) patients, age-matched and middle-aged controls was assessed quantitatively by means of immunohistochemistry using the monoclonal antibody M35. As shown previously in biopsy cortices, mainly layer II/III and V pyramidal neurons were immunolabeled. Neither distribution nor numbers of labeled cells displayed significant differences between the groups investigated. This is in accordance with the results of ligand binding studies that mostly failed to reveal different binding characteristics in AD compared to controls. Muscarinic and nicotinic receptor proteins have been shown to be colocalized in many cholinoceptive pyramidal neurons. Since nicotinic receptors--in contrast to muscarinic receptor proteins--are severely reduced in AD, this indicates a selective impairment of nicotinic receptor expression and not a significant death of cholinoceptive neurons per se.

Aged

Changes in cortical dendritic branching subsequent to partial social isolation in stumptailed monkeys.

Stumptailed monkeys were reared from 1 week after birth to 6 months of age in either a colony condition with the mother or in partial social isolation that allowed visual contact with the colony animals, but not physical contact. At 6 months of age the animals were killed and selected areas of the neocortex stained by the Golgi-Cox method. Relatively nonspiney cells of Layer IV were drawn and analyzed for complexity of dendritic branching. Isolation-reared animals had significantly decreased branching complexity in Motor I cortex when compared to the control animals. A transform of the data that related the number of branches to the number of previous branches showed a slight rearing effect in Somatosensory I cortex with the deprived animals having a lower rate of branching than the controls. We conclude that social isolation also includes a motoric deprivation that could account for these data.

Animals

Olfactory bulb lesions in Alzheimer's disease.

The olfactory bulb (OB), with its comparatively simple and well-delineated connectivity, presents an interesting system for examining cell-specific pathology in neurologic degenerative disorders such as Alzheimer's disease (AD). We have found that in AD the large, efferently projecting neurons (mitral cells) of the OB degenerate, typically without classical Alzheimer neurofibrillary changes. In some cases, with less severe neocortical pathology, the terminal arborizations of olfactory nerve appear hyperplastic and are associated with focal accumulations of A-4 (beta-amyloid) immunoreactivity that are not detectable by standard amyloid stains. These abnormalities may represent a pathologic manifestation of normally occurring plasticity in the olfactory system.

Aged