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D G Flood

Publications and source records attributed to D G Flood.

At least 37 records · Page 2Linked to original sources

Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease.

Different patterns of age-related dendritic change have been reported in different zones of the human hippocampal region in the normal and Alzheimer's disease (AD) brain. In normal aging there is an increase in average (net) dendritic extent (which we interpret as plasticity) in the parahippocampal gyrus and dentate gyrus. There is net stability of dendritic extent in CA2-3, CA1, and subiculum. In regions that show plasticity in normal aging, dendrites in AD show reduced or aberrant plasticity. In regions that show stability in normal aging, dendrites either are stable or regress in AD, depending upon how severely involved the region is with the pathology of AD.

Aged↗

Estimating the number of granule cells in the dentate gyrus with the disector.

A practical example is given of how a newly developed stereological estimator of particle number, the disector, can be used to make estimates of neuron number in the dentate gyrus of rats. The estimates are free of biases related to lost caps, overprojection and assumptions about size, shape and orientation of the objects that are counted. The disector principle and the practical considerations relating to histological preparations and sampling are presented.

Animals↗

Volumes of the components of the hippocampus in the aging F344 rat.

Much of the recent data on cells, synapses, and other structures in the dentate gyrus and hippocampus as a function of age are packing density or volume fraction data. In order to estimate total numbers, volumes, or surface areas of cells, synapses, vessels, etc., as a function of age, the total volumes of the subregions of the dentate gyrus and hippocampus must be known. The volumes of these subregions, visualized with the Timm stain, have been determined in 24 F344 rats from 4 to 37 months of age. Volumes of the various structures showed age-related increases which were statistically significant for the perforant path zone of the dentate gyrus molecular layer, as well as the total molecular layer, the hilus, and regio inferior and total mossy fiber systems. If the 4-month age group is eliminated from consideration, only the ratio of the volume of the mossy fiber zones to the volume of the perforant path zones of the dentate molecular layer increases significantly with age. Our general finding of lack of volumetric reorganization of the subdivisions of the hippocampal region between 12 and 37 months suggests that studies of the packing densities of structures in most of these zones may be considered comparable across ages, assuming comparability of sampling regions.

Aging↗

Dendritic extent in human CA2-3 hippocampal pyramidal neurons in normal aging and senile dementia.

The extent of dendritic trees of pyramidal neurons of the CA2-3 field of the hippocampus of 20 human brains obtained at autopsy was quantified in Golgi Cox-stained tissue. Fifteen cases were neurologically and psychiatrically normal and ranged in age from 43 to 95 years. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of both the apical and basal trees of CA2-3 pyramidal neurons was found to be unchanged from middle age to very old age. This finding of net stability of dendritic extent is in contrast to previous quantitative reports of either continued dendritic growth in human parahippocampal gyrus or of dendritic growth followed by regression in human dentate gyrus. This finding is consistent with the suggestion that changes in dendritic extent in normal aging are a function of the balance between regressive and proliferative influences and are region specific. In cases with SD, dendritic extent of both the apical and basal trees was found to be similar to that of the normal age-matched cases. These data are consistent with those of others suggesting relative sparing of the CA2-3 field from the degenerative changes in senile dementia.

Adult↗

Dendritic extent in human dentate gyrus granule cells in normal aging and senile dementia.

Granule cells of the hippocampal dentate gyrus of 22 human brains obtained at autopsy were studied in Golgi-Cox stained tissue. Seventeen cases were cognitively normal and ranged from 43 to 95 years of age. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of granule cells was found to increase in normal aging between middle age (fifties) and early old age (seventies). However, dendritic regression was found in the oldest old (nineties). This finding of dendritic regression following growth is in contrast to previous quantitative reports of continued dendritic growth in parahippocampal gyrus of normal aging human brain and suggests that changes in dendritic extent in normal aging are region and age specific. In cases with SD, dendritic extent was greatly reduced when compared with the normal cases of the same age (seventies) and slightly reduced when compared with middle-aged cases. The very old normal and SD cases were similar in dendritic extent, suggesting that the functional and memory deficits characteristic of SD cannot be explained solely on the basis of the static status of dendritic extent of single neurons.

Aged↗

Failed compensatory dendritic growth as a pathophysiological process in Alzheimer's disease.

In normal human aging the remaining neurons of two areas of the hippocampal region have been found to compensate for age-related neuronal loss by proliferating new dendrites. In Alzheimer's disease (AD) the layer II pyramidal neurons of the parahippocampal gyrus fail to show this compensatory response, in spite of a probable, exaggerated disease-related loss of neurons. In AD the dentate gyrus granule cells of the hippocampus also show a reduced amount of the compensatory response. This failure of the AD brain to show the normal compensatory plastic response, seen in normal aging as dendritic growth, may be viewed as one of the pathophysiological processes of the disease.

Aged↗

Age-related dendritic growth in dentate gyrus of human brain is followed by regression in the 'oldest old'.

Dendritic extent in dentate gyrus granule cells of normal aging human brain was found to increase between middle age (fifties) and early old age (seventies). However, dendritic regression was found in the oldest old (nineties). This finding of dendritic regression following growth is in contrast to previous quantitative reports of continued dendritic growth in parahippocampal gyrus of aging human brain. This new result reinforces the concept of age and region specificity in changes in dendritic extent.

Adult↗

Stability of numbers but not size of mouse forebrain cholinergic neurons to 53 months.

In normal mammalian aging there is a reduction of cholinergic markers in a variety of regions. To determine whether this reduction is related to reduced numbers of basal forebrain cholinergic neurons, we counted the number and measured the sizes of the magnocellular acetylcholinesterase-positive neurons in this region of 7, 15, and 53-month-old C57Bl/6NNIA mice. Data were collected from coded slides containing the medial septum, nucleus of the diagonal band, magnocellular preoptic nucleus, and nucleus basalis magnocellularis. There was no decline in numbers of basal forebrain acetylcholinesterase-positive neurons in any of the regions studied. However, cell sizes showed a progressive age-related decline which was greatest in the nucleus basalis magnocellularis.

Acetylcholinesterase↗

A Golgi study of hypothalamic transplants in young and old host rats.

The supraoptic nucleus of the F344 rat shows an age-related dendritic regression. In order to determine whether this previously observed dendritic regression may have been related to extrinsic (to the cell) hormonal, neurotoxic, or other circulating factors unique to the hypothalamus of older brains, we conducted a quantitative Golgi study of F344 embryonic anterior hypothalamic transplants into the third ventricle of young adult (5 months) and older (25 months) male F344 rats. Three months following transplantation there were no qualitative effects of host age on neuronal morphology, nor were there quantitative effects on transplant size, dendritic length or branching frequency within the transplanted tissue. These results suggest that either (a) there were no age-related changes in factors in the host brain which were sufficient to significantly affect dendritic extent or, (b) intrinsic connections or other properties within the transplant may be important in moderating the effect of the milieu of the aged brain on the transplanted tissue.

Aging↗

Selective damage to large cells in the cat retinogeniculate pathway by 2,5-hexanedione.

The neurotoxic hexacarbon 2,5-hexanedione (2,5-HD), which produces transport abnormalities and swellings in the large diameter fibers of the peripheral nervous system, was administered to cats in an attempt to produce similar selective effects in the optic tract. Anatomical findings indicate damage to one type of retinal ganglion cell, the large (alpha) or Y-cell class, both during dosing and after a long recovery period. This selective involvement of the large ganglion cells during dosing was shown by decreased retrograde transport of HRP in these cells relative to smaller cells. Such selectivity was not apparent in axonal swellings and neurofilament accumulations which were present in fibers of all diameters in the distal optic tract. Visual threshold studies during dosing showed a loss of flicker resolution with preservation of visual acuity, a result consistent with the different physiological properties of alpha and beta ganglion cells. In one cat, which survived dosing for a period of 8 months, there was a dramatic reduction in the number of large cells and a pronounced shrinkage of those that remained, but no observed changes in other cell types. Thus, this intoxication caused (1) axonal swellings which were not selective for fiber size; (2) a selective defect in axonal transport with later neuronal degeneration and shrinkage that were limited to large cells; and (3) a loss of flicker resolution that may reflect dysfunction of large ganglion cells.

Animals↗

The role of area centralis in the spatial vision of the cat.

Spatial contrast sensitivity was measured over a 6 log unit luminance range in two cats before and after bilateral 4-5 deg radius argon laser lesions were placed in area centralis. The lesions reduced high luminance contrast sensitivity by approximately 0.3-0.4 log units at the low and middle spatial frequencies and by 0.5-1.0 log unit at the highest spatial frequencies. The loss of visual acuity was 0.4 octave in the cat with the smaller lesions and 0.8 octave in the cat whose lesions were larger. At lower luminance, little loss in contrast sensitivity was seen and no change was detectable at scotopic luminance levels. Visual acuity, on the other hand, was decreased at higher scotopic conditions, but unaffected at the lowest luminance levels tested (16 X 10(-6) cd/m2). These data indicate that area centralis plays an important role in detecting both high and low spatial frequencies under high luminance conditions but contributes only to spatial resolution at low luminance levels. This result is consistent with known anatomical and physiological properties of the cat area centralis.

Animals↗

Species difference in circadian [14C]2-deoxyglucose uptake by suprachiasmatic nuclei.

Hamsters exhibited a circadian variation in metabolic activity determined by [14C]2-deoxyglucose uptake in the suprachiasmatic nuclei, as has been previously reported for rats. The 13-line ground squirrel, a diurnal rodent, did not show a circadian variation in metabolic activity. The data are consistent with the hypothesis that there is a basic difference in the functional organization of the suprachiasmatic nuclei in nocturnal and diurnal animals.

Animals↗

Spatial sampling by dendritic trees in visual cortex.

Kittens were reared in vertically or horizontally striped cylinders. After rearing exposures of 400-500 h, responses of single neurons were determined as a function of orientation of a square wave grating stimulus. These data suggest that the rearing environment did alter orientation preference in some of the kittens. The visual cortices of the stripe-reared kittens and of control kittens were impregnated according to a Golgi-Cox method. Dendrites of layer IV stellate cells were tracked and analyzed in three dimensions by a computer-microscope. Four methods of analyzing the spatial distribution of dendrites are described and discussed. Two methods previously described in the literature were not sufficiently sensitive to detect any differences among kittens exposed to vertical or horizontal stripes or to a control environment. Two newly developed methods were able to provide initial evidence for rearing effects on dendritic trees in visual cortex. The more detailed of these new methods describes the angular location of dendritic segments, with respect to standard brain axes, as a function of distance from the cell body. Data obtained by means of this method of dendritic angular distribution (DAD) plots suggests a number of conclusions. Rearing animals in a striped environment may influence the way in which dendrites of layer IV stellate cells of visual cortex distribute themselves in the neuropil. The effect of selective rearing on dendritic distribution does not appear to extend back to those portions of the dendritic tree closest to the cell body. This influence of rearing in a selective environment may be explained by hypothesizing that during development dendrites distribute themselves in ways that tend to maximize the effects of spatiotemporal summation for the postsynaptic neurons.

Animals↗

Stability of dendrites in cortical barrels of C57BL/6N mice between 4 and 45 months.

Qualitative and quantitative studies of dendritic parameters were conducted on Golgi-impregnated layer IV spiny stellate neurons in the posteromedial barrel subfield (PMBSF) of somatosensory cortex of the C57B1/6N mouse. Three mice each, at 4, 12, 22, 26, 30, 36 and 45 months of age were studied. No qualitative changes were observed among animals of different ages. The quantitative data indicated that dendritic length and numbers of segments remained unchanged over all ages studied.

Aging↗

Neuron numbers and dendritic extent in normal aging and Alzheimer's disease.

Factors which limit the interpretation of studies of aging brain include: secular trends, species and strain differences, effects of tissue processing, and bias which may be introduced at many levels of an experimental design. With these limitations considered, evidence is reviewed regarding neuron numbers and dendritic extent in normally aging rodent, monkey and human brain and in Alzheimer's disease. It is concluded that neuron loss and change in dendritic extent in normal aging are regionally specific, and that corresponding brain regions do not always change in similar ways in rodents and primates. It is suggested that such differences may, in part, be due to inconsistent definitions of 'aged' among species. In Alzheimer's disease there is excess neuron loss and dendritic regression in some, but not all, brain regions. Measures of the morphological substrates of brain function show appreciable overlap between AD and control groups. It is hypothesized that the static, post-mortem status of brain morphology may not adequately reflect the functional capabilities of the dynamic morphology of the living brain.

Aging↗