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Biomedical subjects

A P Fotheringham

Publications and source records attributed to A P Fotheringham.

12 recordsLinked to original sources
PubMed2004

The glial cell response to a viral vector in the aged brain.

The normal aged brain undergoes pro-inflammatory changes. We investigated the effect of injecting a potential inflammatory stimulus, an adenoviral vector, on the response of microglia and astroglia in the aged brain. Groups of young (4 months) and old (31 months) male C57BL/Icrfat mice received a unilateral injection into the striatum of adenoviral vector encoding the LacZ gene. After 48 h, the mice were killed and the brains analysed for numbers of activated microglia and macrophages using the biotinylated lectin Griffonia simplicifolia as a marker; astroglia were identified by immunohistochemistry for glial fibrillary acidic protein (GFAP). The cell counts were analysed using two-way analysis of variance (anova). Transgene expression was assessed by beta-galactosidase histochemistry. The numbers of activated microglia in the striatum increased in response to the adenovirus in both young [contralateral 19.5 (3.7), ipsilateral 36 (3.0)] and old [contralateral 23.1 (9.6), ipsilateral 40.8 (6.9)] mice (two-way anova; P < 0.0001), but there was no significant difference between the two age groups. There was a significant age-related increase in the number of GFAP-positive astroglia in the uninjected, contralateral striatum [4 months, 2.5 (1.4); 31 months, 29.7 (9.3)] (two-way anova; P < 0.0001). However, there was no difference in response to the adenovirus in both young [contralateral 2.5 (1.4), ipsilateral 3.2 (1.2)] and old [contralateral 29.7 (9.3), ipsilateral 28.9 (8.2)] mice. We conclude that even though it has been argued that the aged brain is in a pro-inflammatory state, under the experimental conditions used in this study, there was no difference in the nature of the immune response between young and old mice of this strain to an adenoviral load.

Adenoviridae↗
PubMed2000

Oedema and glial cell involvement in the aged mouse brain after permanent focal ischaemia.

This study examines the effect of age on oedema and brain swelling, and associated glial cell involvement on the size of the lesion in two models of permanent, focal cerebral ischaemia. Ischaemia was induced in male C57BL/Icrfat mice (4-6 and 26-31-month-old) by middle cerebral artery (MCA) occlusion using either electrocoagulation after craniotomy (MCA/craniotomy), or by an intraluminal filament through the carotid artery (MCA/icf). Twenty-four hours after inducing ischaemia, brain swelling and lesion size were measured in young and aged mice, and cerebral oedema by wet/dry brain weights. Histopathology and immunocytochemistry were performed on a separate set of perfusion fixed brains. The MCA/icf technique produced a significantly larger lesion than MCA/craniotomy in both age groups. The percentage of water taken into the brain was significantly greater after MCA/icf, with aged mice showing the greatest increase. When lesion size was corrected for brain swelling there was no age-related increase in the size of the lesion. The numbers of microglia and astroglia increased significantly in the parietal cortex of aged control animals, and there were qualitative differences in the glial response between the two stroke models. This study emphasizes the importance of age in models of permanent focal ischaemia, with oedema clearly being a significant factor. Differ-ences in the responsiveness of the glial cell population with age may be of fundamental importance in the progress of ischaemic brain damage.

Aging↗
PubMed1991

Age-associated changes in neuroaxonal transport in the hypothalamo-neurohypophysial system of the mouse.

In this study, we investigated age-associated changes in neuroaxonal transport of the hormone vasopressin (AVP) and its associated neurophysin (NPII), from the supraoptic nucleus (SON) of the hypothalamus to the neurohypophysis. C57BL/Icrfat male mice of 6 and 28 months of age were injected in the hypothalamus with L-[35S]cysteine. Animals were killed up to 2.25 h after injection and NPII and AVP from the SON and neurohypophysis were separated using HPLC, and the fractions counted for radioactivity. In the SON, radiolabelled NPII and AVP were first detected after 0.50 h in both young and old mice. There was no significant difference between the age-groups in the incorporation of radiolabel over the time course studied. Radiolabelled NPII in the neurohypophysis was significantly above background after 1.25 h in the young, and after 1.50 h in the old mice. The differences between the two age groups was significant (P = 0.05). Radiolabelled AVP followed a similar trend, but was not significantly above background until 1.50 h in the young and 1.75 h in the old. The differences between the two age groups was on the point of significance (P = 0.056). These results indicate a significant reduction of up to 25% in the rate of axonal transport of neurohypophyseal peptides with advancing age.

Aging↗
PubMed1989

Age-associated changes in the kidney of the laboratory mouse.

This paper describes a qualitative and quantitative morphological investigation of the kidneys of male laboratory mice without macroscopic pathology at 6, 12, 24 and 34 months of age. In the 6- and 12-month old adults there were no signs of microscopic pathological changes in either the kidney cortex or medulla. However, at 24 and 34 months of age minor pathology, such as focal interstitial inflammation, was detected. In both these age groups there were a few glomeruli with sclerotic changes. There were no significant differences in the total volume of the kidneys, cortex, medulla or other structures with age. There was a significant increase in the diameter of the glomeruli with age but no change in the total numbers of glomeruli. The increase in volume of the glomerulus appears to be due to cellular components rather than changes in the blood vessels. It is concluded that in animals without macroscopic pathological changes there are only minor alterations in kidney structure with age, and that any alterations which do take place occur very late in the life span.

Age Factors↗
PubMed1987

The effect of vitamin E deficiency on the induction of age pigment in various tissues of the mouse.

The effect of a dietary deficiency of vitamin E on the concentrations of lipofuscin in the hippocampus and the supraoptic nucleus (SON) of the hypothalamus, and in adrenal cortical cells was assessed in male mice. The animals were fed either a control diet or the vitamin E deficient diet after 2 months of age for a period of 6 months. There was no significant difference in the growth curves of the 2 groups of animals over the period studied. Fluorescence microscopy and transmission electron microscopy were used to assess the effect of the diet on lipofuscin in the different tissues. Quantitative morphological techniques were used to determine the relative volumes of lipofuscin in the neurons from the SON and in the adrenal cortical cells. There was no significant difference in the concentration of lipofuscin in the SON neurons after vitamin E deficiency but there was a significant increase in the adrenal cortical cells. There was a clear difference in the effect of the deficiency on mitotic and fixed post-mitotic cells over the period investigated but further studies would be necessary to determine whether or not there was a critical period in the life span where vitamin E deficiency may induce changes in all cell types.

Adrenal Cortex↗
PubMed1985

The effect of age on the control of water conservation in the laboratory mouse--metabolic studies.

Age-related changes in the intake of food and water, and the output of faeces and urine were investigated in C57BL/Icrfat mice of 6 and 24 months of age. Animals were singly housed in a metabolic cage for a period of 30 days. 14 days were allowed for acclimatization before the animals were dehydrated for 24 hours. 10 days of rehydration were allowed prior to a hyperosmotic challenge with 3% sodium chloride in the drinking water. The animals were then observed for 5 more days of rehydration. Urine was collected and analysed with regard to sodium, potassium, urea and vasopressin output/24 hours (/100g body weight), and the osmotic pressure of the urine was determined. Data were analysed by a 2 factor analysis of variance with repeated measures on one factor. Significant changes were detected in the control of body weight, potassium, sodium and urea outputs. No age-differences were detected in the intake of food or water, the output of faeces or urine, the urine osmotic pressure or the excretion of vasopressin. However, significant changes in these variables were detected in both age groups on the days of physiological challenge. The conclusion drawn is that in the mouse strain studied, and for the period of the lifespan investigated, there is no age related defect in the secretion of vasopressin. However, there are trends in the data suggesting a decreased responsiveness of the kidney with age.

Age Factors↗
PubMed1984

The effect of osmotic challenge and subsequent rehydration on the aging hypothalamo-neurohypophyseal system. A quantitative morphological study of the supraoptic nucleus.

The neurons of the supraoptic nucleus (SON) of male C57BL/Icrfat mice at 6 or 28 months of age were examined from normally hydrated, osmotically loaded and osmotically loaded/rehydrated animals. Using quantitative morphological techniques it was shown that the majority of the ultrastructural variables investigated were controlled in the same way in the SON neurons of young and old mice. The major exception was the mitochondrial compartment which although maintaining a constant proportion of the volume of the SON cell did show a significant reduction in the number of mitochondria in the old group, particularly during the osmotic challenge period of the experiment. The "lipid" body compartment of the SON neuron also behaved differently in the cells from the older age group. This study when viewed in conjunction with previous investigations suggests that these SON neuroendocrine neurons from old animals are able to produce hormone until late in the life-span. However, other aspects of cellular activity appeared to be altered when judged by morphological criteria. It is concluded that the SON neurons from these old mice are able to synthesize hormone-containing organelles to the same concentration as the cells from a younger animal. However, the efficiency of the process, or at least the efficiency of concomitant cellular processes, must be questioned in view of the alterations in the rough endoplasmic reticulum, mitochondrial and lysosomal systems.

Aging↗
PubMed1981

The influence of age on the response of the supraoptic nucleus of the hypothalamo-neurohypophyseal system I. Ultrastructural aspects.

The influence of age on the response of the supraoptic nucleus (SON) of the hypothalamo-neurohypophyseal system to physiological stress has been studied by means of the electron microscope. An osmotic load was applied to male C57BL/Icrfat mice at 6 and 28 months of age and the resulting changes in the ultrastructure of SON cells in response to this stress analysed. In the young animals the differences in morphology observed between the SON cells from control and from those of salt-loaded mice were very similar to those seen in salt-stressed rats at a similar age. Qualitative differences were noted in several sub-cellular components of old, salt-stressed mice. The mitochondria showed evidence of ultrastructural damage in cells from the old, stressed animals. The Golgi system and the rough endoplasmic reticulum both showed heterogeneity in structure when compared with cells from young salt-stressed mice. In addition, there was a decrease in the lipofuscin content of old, salt-stressed mice. These changes are discussed with respect to the overall efficiency of cellular activity in old, physiologically stressed animals.

Aging↗
PubMed1980

The influence of age on the hypothalamo-neurohypophyseal system of the mouse: a quantitative ultrastructural analysis of the supraoptic nucleus.

A quantitative study of various morphological parameters in endocrine cells of the neuroendocrine region of the laboratory mouse was carried out. The supraoptic nucleus of the hypothalamo-neurohypophyseal system synthesises the hormones vasopressin and, to a lesser extent, oxytocin, and transports them to the posterior pituitary. Female C57BL/Icrfat mice at 8 and 26 months of age, free of macroscopic pathology, were sampled when in a physiologically defined resting state. No significant differences in the volume fractions of most cell and subcellular components could be detected at the two ages studied; however, significant increases in the volume fractions of hormone-containing granules and lipofuscin (aging pigment) were demonstrated in older animals. These observations are similar to those made on rat endocrine pancreas also in the resting state. The notion that these hormone-secreting cells are "protected" to some extent from the aging process, and may have some of the qualities of "pace-maker" cells, is discussed.

Aging↗
PubMedDate not supplied

Age-related postreceptor mechanisms: changes in adenylate cyclase but not phosphodiesterase in isolated mouse renal medullary collecting ducts.

Urine concentrating ability declines with increasing age, partly due to an impaired response of kidney medullary collecting ducts to the antidiuretic hormone, vasopressin. We investigated this change in isolated mouse medullary collecting ducts by measuring the activity of adenylate cyclase and phosphodiesterase, which catalyse the formation and hydrolysis of cAMP, respectively. Adenylate cyclase activity was measured in the presence of vasopressin (which stimulates adenylate cyclase via the receptor) or forskolin (which directly stimulates the catalytic subunit). We showed an age-related decrease in the catalytic subunit of adenylate cyclase, and no difference in the activity of phosphodiesterase, indicating that a reduction in the catalytic subunit of adenylate cyclase contributes towards the age-related decrease in cyclic AMP response of kidney to vasopressin.

1-Methyl-3-isobutylxanthine↗