PubMed Health⌕ Search

Biomedical subjects

J W Hinds

Publications and source records attributed to J W Hinds.

At least 19 recordsLinked to original sources

Population dynamics of adult-formed granule neurons of the rat olfactory bulb.

The population dynamics of internal granule cells in the rat olfactory bulb during adult life were analyzed in histological sections and in autoradiograms with (1) counts of granule cells, (2) counts of labeled granule cells 1 month after injection of 3H-thymidine at various ages, and (3) counts of labeled granule cells at varying survival times (up to 18 months) after injection at 3 months and 24 months. The total number of granule cells increases linearly throughout life, approximately doubling between 3 and 31 months. Autoradiographic studies show that the rate of production of new granule cells decreases from 3 to 12 months and then is approximately constant during the rest of the life span. The number of labeled cells found 6 months after injection at 3 and 24 months is about one-fourth and one-half, respectively, that of the number at a 1-month survival, suggesting that many of the cells produced to do not survive. However, at least some granule cells labeled at 3 months survive for 18 months. A model is suggested in which granule cells are produced continuously throughout life and control of the total number of granule cells is effected chiefly through the rate of cell death.

Age Factors↗

Aging in the rat olfactory system: relative stability of piriform cortex contrasts with changes in olfactory bulb and olfactory epithelium.

Previous studies have quantified growth and atrophy of the olfactory bulb and olfactory epithelium of the Sprague-Dawley rat from maturity to senescence. Major events occurring in these structures include changes in the volume of mitral cells and changes in the number of septal olfactory receptors. These effects are large, consist of a growth phase followed by atrophy, and are temporally related in that events in the olfactory epithelium precede those in the mitral cells. A hypothesis of aging based on transneuronal effects would predict that these changes would be similarly transmitted to the next synaptic station in the olfactory pathway. Therefore, cells and synapses of the piriform cortex were studied in rats 3, 12, 18, 24, 27, 30, and 33 months of age. Alternate Vibratome sections through brains perfused with mixed aldehydes were processed for light and electron microscopy. No significant age effects were found for the volumes of cortical laminae Ia and Ib. Both numerical and surface density of synaptic apposition zones in layer Ia, formed primarily by mitral cell axons, were stable with age. A modest (18%) but significant decline in the proportion of layer Ia occupied by dendrites and spines was mirrored by an increase in the proportion of glial processes; no change in the proportion of axons and terminals was observed. Neither nuclear volume, nor soma volume, nor numerical density of layer II neurons changed with age. Thus, contacts made in the piriform cortex by mitral cell axons remain relatively stable in senescence, despite the marked volumetric changes in the mitral cell somata, changes which were confirmed again in this study. Age-related dendritic regression in layer II neurons may be attributable to functional deafferentation subsequent to reduced receptor input to mitral cells.

Age Factors↗

An autoradiographic study of the mouse olfactory epithelium: evidence for long-lived receptors.

In order to try to determine whether differentiated olfactory receptors turn over (die and are replaced by newly differentiated cells) during adult life, mice were injected with a single dose of 3H-thymidine at either 2 or 4 months of age and allowed to survive for up to 12 months; they were caged in a laminar flow unit to prevent rhinitis. Counts of labeled receptor cells detected autoradiographically after injection at 2 months of age revealed that, following an initial decrease from 1 to 3 months of survival, numbers of labeled cells remained approximately constant, at least up to 12 months of survival. Cells still labeled at 12 months of survival were confirmed as receptor cells by electron microscopic examination of reembedded sections. The hypothesis is suggested that in the absence of disease-related destruction of the olfactory epithelium, most or all receptor cell turnover represents newly formed cells that fail to establish synapses with the olfactory bulb; fully differentiated receptor cells may be quite long-lived.

Animals↗

Intranuclear inclusions in rat piriform cortex: increase with age and preferential location within superficial layer II.

Intranuclear inclusions have been observed in layer II neurons of rat piriform cortex. These inclusions have the form of a filamentous lattice and resemble those described by others previously. The frequency of lattice-containing nuclei shows a significant fourfold increase over a period of 3-33 months of age, with the largest increase occurring after 18 months. The incidence of these inclusions is highest in the superficial third of layer II and is significantly greater than what would be expected from the distribution of all neuronal nuclei in layer II. The presence of intranuclear lattices may be related to the high level of electrical activity in piriform cortex, and their increase with age may reflect a long-term cumulative effect of this activity.

Aging↗

Variation in longevity of rats: evidence for a systematic increase in lifespan over time.

Male-Sprague-Dawley rats (CrL:CD(SD)BR) were maintained under barrier conditions at Charles River Breeding Laboratories (Wilmington MA) from August, 1975, to July, 1983. Animals were provided food and water ad libitum. Survival data from 8 completed cohorts of 100 animals each and one continuing cohort reveal a highly significant linear increase in median lifespan, yielding a 26% increase in this parameter for cohorts born over a period of less than six years. The biological factors responsible for this increase are not clear at present. Nevertheless, these results in outbred rats, taken in conjunction with previous observations of a trend towards increased longevity in inbred mice, indicate that the assumption of cohort equivalence underlying many cross-sectional studies of biological aging may not be valid.

Aging↗

Effects of sensory deprivation on the developing mouse olfactory system: a light and electron microscopic, morphometric analysis.

Closure of the nostril by electrocauterization on postnatal day (PN) 1 or 2 was used to study effects of olfactory deprivation on developing olfactory epithelium (OE) and bulb (OB) in CD-1 mice. No damage was observed in OE sections 1 or 3 days after closure, and at PN 30 no difference was found in the number of OE receptors between closed and open sides. Odor deprivation and a decrease in functional activity in experimental bulbs was evident from deoxyglucose autoradiographs at PN 21 and PN 30. At PN 30 deprived bulbs appeared smaller than nondeprived bulbs. Nissl stains revealed normal cytoarchitecture, but a protargol stain demonstrated fewer intraglomerular dendrites in deprived bulbs. At PN 30, volumes of deprived bulbs were 26% smaller than nondeprived bulbs. The volume of each bulbar lamina was 13 to 35% smaller than the comparable nondeprived lamina except for the ventricular/subependymal zone which was not significantly different between bulbs. Volumes of bulbs contralateral to the closed naris and the volumes of their laminae were not significantly different from control bulbs, suggesting no hypertrophy of nondeprived laminae. Deprivation did not affect the number of mitral cells seen at PN 30, their nuclear size, or their number of nucleoli. Lateral olfactory tract cross-sectional area was also unaffected by deprivation. Mitral cell perikaryal size, however, was smaller in deprived bulbs. Soma surface areal density of deprived mitral-to-granule cell synapses in deprived bulbs was 65% of the nondeprived density, while the density of granule-to-mitral cell synapses was only 46% of the nondeprived density. It is concluded that neonatal naris closure brings about a functional deprivation of the OB without receptor degeneration. Neonatal olfactory deprivation affects the perikaryal surface area but not the number of mitral cells. Also, deprivation markedly affects the reciprocal synapses between mitral and granule cells. Olfactory sensation thus appears necessary for normal development of OB neurons and synapses.

Animals↗

Development of retinal amacrine cells in the mouse embryo: evidence for two modes of formation.

Developing amacrine and ganglion cells have been graphically reconstructed from a series of 567 consecutive thin sections of the E17 mouse retina on the first day when an obvious inner plexiform layer (IPL) is present and 2 days later than for our previous study of amacrine cell formation at E15 (Hinds and Hinds ('78). At E17 amacrine cells of the neuroblastic layer (normally placed amacrine cells), unlike those at E15, appear to develop directly from ventricular cells; intermediate elements are bipolar-shaped cells with terminal arborization in the IPL. On the other hand, the development of displaced amacrine cells and some normally placed amacrine cells at E17 appears to closely resemble that described for all amacrine cells at E15: derivation from "ganglion cells" by loss of the axon and transformation of the cell. Three lines of evidence support this conclusion. (1) Cells have been found that resemble ganglion cells except that they have only an apparent axon remnant and have somata restricted to the IPL and the immediately adjacent portion of the ganglion cell layer (GCL); amacrine cells transitional between these cells and the smaller and darker, normally placed amacrine cells also occur in the IPL. (2) Axons of two ganglion cells have been found which appeared to be in the process of breaking up and degenerating. (3) The fraction of anaxonic cells with somata in the GCL (two out of 79, or 3%) or in the GCL plus IPL (ten out of 88 or 11%) is too small to account easily for the large fraction (probably at least 45%) of displaced amacrine cells found in the adult, even with conservative assumptions (P less than 0.05). A mathematical model suggests that approximately 40% of the ganglion cells present at E17 will lose their axon, and of these around half will migrate to the neuroblastic layer, while the other half will become displaced amacrine cells. The results suggest a natural explanation for the recent finding that wide field amacrine cells are found with somata on both sides of the IPL, while narrow field amacrine cells are never displaced: the former may be derived from ganglion cells by loss of the axon, while the latter may be formed directly from ventricular cells.

Animals↗

Stability of synaptic density and spine volume in dentate gyrus of aged rats.

The number of synapses per unit volume and per granule cell and the size of dendritic spines were studied in the dentate gyrus of Sprague-Dawley rats 6, 24, and 30 months of age. Neither synaptic density nor mean spine volume showed any age-related trends. An increase in granule cell packing density at 24 months and concomitant stability of the height of the granule cell layer is consistent with the idea that postnatal generation of granule cells may continue late into life. Possible explanations for the discrepancies in the literature regarding synaptic loss in this area include differences in morphometric techniques, age of animals used, regional differences within dentate gyrus, and sampling variability. Generalized synapse loss in the senescent rodent brain remains to be established.

Aging↗

Capillaries in aging rat olfactory bulb: a quantitative light and electron microscopic analysis.

Olfactory bulbs from Charles River (Crl) rats from 3 to 36 months have been examined with light and electron microscopy. Total capillary length, surface, and volume, as well as number of endothelial cells, increases during the twofold increase in olfactory bulb volume from 3 to 18 months, but the relative density of these parameters shows no change during this time; from 18 to 36 months when neuronal cell body and dendrites are decreasing markedly in size, the relative density of capillaries shows only a modest decrease. Capillary lumen size and capillary wall thickness remain the same throughout life, but basal lamina thickness doubles from 3 to 24 months and then remains constant from 24 to 36 months. The incidence of several unusual ultrastructural features of the outer capillary basal lamina has been shown to increase with age.

Aging↗

Aging in the rat olfactory system: correlation of changes in the olfactory epithelium and olfactory bulb.

Two regions closely linked synaptically (olfactory epithelium and olfactory bulb) have been compared in an age-graded series of rats. Previous findings of growth and atrophy of constituent elements in Sprague-Dawley Wisconsin (SD) rats have now been confirmed in Charles River (Crl) rats. In the olfactory bulbs of Charles River (Crl) rats, the volume of layers, the number of olfactory axodendritic synapses in the glomeruli, the total volume of glomerular dendrites, and the size of mitral cell bodies all approximately double between 3 and 24--27 months, and then all decrease by 36 months. Unlike SD rats, however, no loss in the number of mitral cells occurs in Crl rats, and the increase in volume of the olfactory bulbs from 3 to 24 months is approximately double that of SD rats. In the olfactory epithelium the total number of septal olfactory receptors more than doubles between 3 and 18--24 months and then declines markedly, as does the volume of olfactory axons in olfactory bulb glomeruli. Comparison of the regression lines for change in number of septal receptors with that of the size of mitral cell bodies discloses that the decline in number of receptors begins several months earlier than the decline in mitral cell size. This suggests that the atrophic changes in the olfactory bulb may in part be secondary to changes in the receptors of the olfactory epithelium. Numbers of synapses in the glomeruli appear to decline less markedly with age than the number of receptors, and a significant increase in number of synapses per receptor occurs in the oldest group studied (33 months), suggesting a compensatory increase in the relative number of synapses per receptor in the surviving receptors.

Aging↗

Preservation of retinal structure in aged pigmented mice.

The effects on the retina of advancing age were studied in pigmented mouse strain (C57BL/6J). The mice range in age from 65 days to 1000 days, an age well beyond the mean life span of the population (850 days). The thickness of the neuronal and plexiform layers and the planimetric density and size of the component neurons were assessed in both central (200-500 micrometers from the optic disc) and peripheral (within 200 micrometers of the retinal margin) areas. In addition, the overall size of the retina was determined by measuring its length along the horizontal meridian. Although retinas of albino rodents degenerate extensively during aging [10, 18, 31, 32, 40], in the retinas of pigmented mice neither the central nor the peripheral locus showed either marked thinning of the retinal layers or neuronal loss with advancing age. We suggest that previous findings of severe retinal degeneration in albino rodents during aging can be attributed to their lack of pigment and that pigmented animals offer a more suitable animal model for normal retinal aging.

Aging↗

Gliogenesis of astrocytes and oligodendrocytes in the neocortical grey and white matter of the adult rat: electron microscopic analysis of light radioautographs.

The identification of newly formed glial cells in the normal adult cerebral cortex is unresolved, since the identification of cells incorporating [H3] thymidine has not been demonstrated in the adult by electron microscopy. In the present study, this problem has been studied by combining the resolution of the electron microscope with radioautography of 1-micrometer sections. Four normal male rats were injected at 90 days of age with [H3] thymidine and allowed to survive for 30 days. Labeled cells were found in 1-micrometer sections of the visual cortex of these adult rats, and electron micrographs of selected cells from these same sections demonstrated clearly two types of cells labeled, astrocytes and oligodendrocytes, in both grey and white matter. The few cells that were tentatively identified as labeled microglia in the light microscope proved to resemble oligodendrocytes when examined in the electron microscope. In 1-micrometer sections of the cortical grey matter, heavily labeled astrocytes (13 or more silver grains over the nucleus) represent about 0.08% of the total astrocytic population, and heavily labeled oligodendrocytes also were about 0.08% of their population. In the cortical white matter, about 0.03% heavily labeled astrocytes were observed, compared to about 0.07% heavily labeled oligodendrocytes. For all neuroglial cells in both white and grey matter, the average percent heavily labeled cells was 0.066%, a value large enough to suggest a slow turnover of neuroglial cells during the lifespan of the rats.

Animals↗

Differentiation of photoreceptors and horizontal cells in the embryonic mouse retina: an electron microscopic, serial section analysis.

The early differentiation of photoreceptors and horizontal cells in the mouse retina has been studied with serial thin sections and reconstructions in embryos on the fifteenth and seventeenth days of gestation (E15 and E17). The following developmental sequences have been inferred. At E15 photoreceptors develop from ventricular cells when a long vitreal process fails to develop following mitosis, and the end of the ventricular process forms a bulbous enlargement (the future inner segment) which contains a pair of centrioles and a cilium and extends into the optic ventricle. This future inner segment is considerably larger at E17, but otherwise the photoreceptors resemble those seen at E15. At E15 horizontal cells develop from ventricular cells when a long vitreal process fails to develop following mitosis, and the end of the ventricular process detaches from the junctional complex at the ventricular surface. By E17 future horizontal cells are located in the middle of the ventricular layer (neuroblastic layer) and have developed from bipolar shaped cells into cells with multiple branching processes, predominantly radially arranged but rarely with a more tangential orientation. These relatively advanced cells at E17 resemble closely the earliest stage of horizontal cell formation described previously in silver studies by Cajal. A scheme is proposed which explains the initial differentiation of several of the major cell types in the retina in terms of two key features: whether or not the call remains attached to the junctional complex and whether or not a vitreal process grows into the ganglion cell layer. By independent variations in these two features, four classes of cells are produced that, by virtue of their differing environments, differentiate into four cell types: ganglion (and amacrine) cells, horizontal cells, photoreceptors, and Müller cells.

Animals↗

Rehabilitation following early malnutrition in the rat: body weight, brain size, and cerebral cortex development.

Sprague-Dawley rats were malnourished by giving their mothers an 8% casein diet starting at day 10 of gestation, while controls were fed a 24% casein diet. Starting at postnatal day 20 (P20), rehabilitation of the malnourished animals was attempted by: (1) feeding both mother and young a 24% casein diet, (2) leaving the pups with their mothers until they were 40 days old, and (3) reducing the litter size from 8 to 4 pups. Observations were made on aldehyde-perfused tissue from animals 20, 40 and 70 days old. The somatosensory cortex from one hemisphere was embedded in Araldite, and that from the other side was processed fro Golgi staining. At 20 days of age the body weight of the malnourished animals was 21% that of the controls, but at 70 days it was no longer different. The anterior-posterior length, the width, and the height of the cerebral hemispheres were also significantly reduced at P20, but the differences had disappeared by P70. The thickness of area 3 of the cerebral cortex was measured in 1 micron sections. It was significantly reduced in the malnourished animals at P20, but at P40, following rehabilitation, the difference was no longer statistically significant. In tangential 1 micron sections the fraction of the volume of tissue occupied by neuropil was measured in layers II through IV. At P20 it was significantly reduced only in the upper half of layers II/III of the malnourished animals; at P40 this difference was no longer present. The mean volume of upper layer II/III cell bodies was estimated and found to be significantly reduced in the experimental animals at P20 but not at P40. In the Golgi preparations, pyramidal cells in upper layer II/III were studied. Their estimated volume, as well as the thickness of their basal dendrites, was significantly reduced in the 20 day malnourished animals, but not in the rehabilitated animals. These results show that animals severely malnourished until 20 days of age can reach normal body weight and attain cerebral hemispheres of normal size when proper nutrition is provided. The effects of malnutrition on the cerebral cortex of these animals are most apparent in upper layer II/III which, during the time of nutritional restriction, is the least developed of the cortical layers. However, when proper nutrition is provided, the cerebral cortex may attain normal morphology.

Animals↗

Aging in the rat olfactory bulb: quantitative changes in mitral cell organelles and somato-dendritic synapses.

Quantitative measurements of the major organelles in the mitral cell perikaryon as well as numbers of mitral somato-dendritic synapses, have been made on electron micrographs from rats aged 3 to 30 months. The volume fraction of the cisternae of rough endoplasmic reticulum (RER) is constant throughout the period studied. Hence the amount of RER per cell reflects changes in perikaryal size. Thus there is a 3-fold increase of volume of cisternae of RER per mitral cell from 3 to 27 months and a halving from 27 to 30 months. A similar pattern is seen for the volume of mitochondria per cell. The volumes of dense bodies and cisternae of the Golgi complex per cell show a different pattern, that of a linear increase throughout the period, with no suggestion of a decrease from 27 to 30 months. An interesting finding is that the volume fraction of ground substance (perikaryal cytoplasm exclusive of the measured organelles) shows a remarkably constant value from 3 to 27 months and then a highly significant decrease from 27 to 30 months. This decrease, restricted to the period from 27 to 30 months, suggests a fundamental breakdown in cellular homeostasis in the oldest animals. Numbers of somato-dendritic, mitral-to-granule synaptic junctions per mitral cell and per olfactory bulb show a significant increase from 3 to 24 and 27 months, respectively, and then a suggestive decrease from 24 and 27 to 30 months. This finding indicates that new synapse formation is possible in normal adult rats, perhaps even in quite old rats.

Aging↗