Search PubMedSearch

Biomedical subjects

R M Santer

Publications and source records attributed to R M Santer.

At least 19 recordsLinked to original sources

Morphological evidence for the maintenance of the cervical sympathetic system in aged rats.

Elements of the cervical part of the sympathetic nervous system have been examined quantitatively in four and twenty-four month Wistar rats. The number of unmyelinated axons in the cervical trunk had significantly (P less than 0.002) increased in the old animals and the number of myelinated axons comprised less than 4% of the total number at both ages. The number of neurons in the superior cervical ganglion and the density of noradrenergic innervation of two of its target organs, the iris and the submandibular gland, were insignificantly different at the two ages. These results are consistent with other evidence which suggests that the cervical sympathetic system is maintained throughout the adult lifespan in rats.

Aging

Development of a quantitative histochemical method for determination of succinate dehydrogenase activity in autonomic neurons and its application to the study of aging in the autonomic nervous system.

An accurately validated method was developed for quantitative determination of succinate dehydrogenase (EC 1.3.99.1; SDH) activity in individual sympathetic neuron perikarya by microdensitometric measurement of an SDH-nitroblue tetrazolium-derived formazan final reaction product. Optimal incubation medium and reaction conditions were determined for measurement of reaction product in cryostat sections of rat superior cervical and celiac-superior mesenteric ganglia. The Beer-Lambert laws were verified for the ganglion tissue, and microdensitometric measurements (expressed as mean cell density readings; MCDR/min-1), characteristic of the Michaelis-Menten equation, enabled the results to be used for enzyme kinetic determinations of SDH activity. Km and Vmax values were obtained following Hans linear transformation of the readings. Between the ages of 6-24 months no significant variations in Km values were recorded, indicating an unchanged structure for SDH (overall mean Km = 0.083 +/- 0.055 mM). However, in both ganglia there were significant decreases (ranging from 43-54%) in Vmax values for SDH at 24 months. The overall mean Vmax value at 6 months was 4.01 +/- 0.61 (MCDR) and at 24 months was 2.07 +/- 0.76 (MCDR). This suggests that an overall decrease in metabolic activity takes place with age in sympathetic neurons of the rat superior cervical and celiac-superior mesenteric ganglia.

Aging

Prenatal undernutrition permanently decreases enteric neuron number and sympathetic innervation of Auerbach's plexus in the rat.

The density of the sympathetic innervation and enteric neuron number in Auerbach's plexus has been investigated by glyoxylic acid histofluorescence and by enzyme histochemistry respectively, in the jejunum of adult rats whose mothers had undergone dietary restriction during the last two weeks of pregnancy. Enteric neuron numbers were reduced by 27% and the sympathetic innervation was more sparse, less regularly arranged and showed less fluorescence in the undernourished rats compared to control groups. These results indicate that the effects of maternal undernutrition on the sympathetic and enteric nervous systems are long lasting in the offspring and also that the terminal parts of the sympathetic neuron, as well as the cell body, are susceptible to a nutritional insult.

Animals

Isobestic wavelength determination for succinic dehydrogenase-nitroblue tetrazolium-derived formazans in autonomic neurons.

Two methods have been used to determine the isobestic (equiconcentration) wavelength of formazans derived from nitroblue tetrazolium-succinate dehydrogenase (EC 1.3.99.1) activity in cryostat sections of the rat superior cervical ganglion prior to microdensitometric measurements. Both methods indicate that maximal absorbance of the final reaction product is at a wavelength of 540-550 nm. This wavelength differs by 35-45 nm from that used to measure the same reaction product in sections of other rat tissues such as liver and implies that it may be unwise to adopt a "standard" wavelength for a particular reaction product when making microdensitometric measurements in relation to quantitative enzyme histochemistry.

Animals

Morphometric studies on the microvasculature of pre- and paravertebral sympathetic ganglia in the adult and aged rat by light and electron microscopy.

Morphometric measurements have been made by light and electron microscopy on sections of perfused sympathetic ganglia from rats of 6-24 months of age with special reference to the microvascular bed. Capillaries, postcapillary venules and small venules comprised the majority of the vessels studied but small arterioles were, in addition, included in the light microscopical part of the study. Light microscopical measurements using image analysis showed that there was a decrease in the density of the microvascular bed (number of vascular profiles/area) and in the total vascular luminal area with age in both ganglia. The ratio of neurons to microvessels remained constant in the superior cervical ganglion (SCG) but decreased with age in the coeliac-superior mesenteric ganglion (CSMG). However, the distribution of microvessels in relation to individual neurons remained unchanged throughout life in both ganglia. Ultrastructural studies revealed fenestrations in 12% of SCG microvessel profiles and in 38% of CSMG microvessels at 6 months, but the percentage of fenestrated profiles in the CSMG had declined by 24 months. There were no significant differences in the number of fenestrations per fenestrated profile. The basal lamina surrounding the microvessels increased significantly (almost doubling) in thickness with age. The range and distribution of microvessel wall thicknesses, expressed as harmonic mean wall thickness, were comparable in both ganglia at both ages and increased linearly according to the amount of pericyte covering present. No consistently significant relationships could be discerned between the microvessel wall thickness and luminal diameter or between the wall thickness and the area available to a given volume of blood for exchange of metabolites (luminal perimeter/luminal area). We conclude that the ganglionic capillary bed is similar in both ganglia and, in old age, accommodates structural changes that occur in the ganglion by maintaining its structure and relationship to individual neurons.

Age Factors

Image analysis of the sympathetic innervation of the myenteric plexus in the small intestine of mammalian species.

1. The arrangement of the sympathetic innervation of the myenteric plexus varies between mammalian species. 2. In larger mammals the density of sympathetic innervation of the myenteric plexus is significantly less than in small (less then 1 kg) species. 3. The number of varicosities on the terminal parts of sympathetic neurons innervating the gut is significantly less in larger mammals.

Animals

Morphometric studies on pre- and paravertebral sympathetic neurons in the rat: changes with age.

Morphometric measurements have been made on rat sympathetic neurons at ages between 6 and 24 months. In neurons of the coeliac-superior mesenteric ganglion there is a marked decrease in the neuronal packing density between 12 and 18 months which is accompanied by increases in the size of the neurons and their nuclei. In the superior cervical ganglion, no changes in packing density are seen until 18 months after which a decrease occurs, accompanied by slight increases in the neuronal parameters. These post-maturation changes occurring throughout adult life reveal a continued dynamism of sympathetic neurons into old age as well as revealing further differences between populations of sympathetic neurons.

Aging

A quantitative study of the effects of age on the noradrenergic innervation of Auerbach's plexus in the rat.

Noradrenergic nerves were demonstrated in stretch preparations of Auerbach's plexus and longitudinal muscle from the proximal jejunum of Wistar rats using glyoxylic acid-induced fluorescence. The density of the noradrenergic nerve plexus and the number of nerve terminal varicosities/frame area were assessed using a Quantimet 800 image analyser and the number of varicosities/unit length of nerve was measured manually with a calibrated planimeter. With increasing age, especially between 12 and 18 months there occurs a breakdown of plexus regularity and noticeably reduced levels of axonal fluorescence. Image analysis showed a decrease in the total area of the plexus of more than 50% and a decrease of almost 75% in the total number of varicosities. The frequency of varicosities per 100 micron of axon decreased from 18.79 at 12 months to 14.79 at 18 months. Significant changes in these parameters did not occur during the following 6 months. The dramatic decrease in the density of the noradrenergic innervation of Auerbach's plexus and the fall in number of varicosities with age implies a reduction in the potential of the sympathetic nervous system to influence control over motility of the jejunum in the aged rat.

Aging

Enteric neuron numbers and sizes in Auerbach's plexus in the small and large intestine of adult and aged rats.

Neurons in the myenteric plexus of Auerbach of the jejunum, ileum, colon and rectum in 6- and 24-month-old rats have been visualised by an enzyme histochemical method in laminar preparations of the muscularis externa. Neuron somata numbers and sizes were recorded in the preparations. Significant reductions, of at least 40%, in the numbers of neurons in the ganglia of the myenteric plexus of the 24-month animals were recorded in all regions of the intestine, especially in the colon where the neuron number decreased by over 60%. These figures do not take into account changes that might have occurred in the overall length of the intestine during adult life. Measurements of neuron sizes suggest that the neuronal fall-out with age affects all categories of neuron equally and implies that all the intrinsic neuronal systems of the gut could be equally affected in old age.

Aging

Effects of prenatal undernutrition on prevertebral sympathetic neurons in the rat: a morphological and fluorescence histochemical study.

The effects of maternal undernutrition during the last seven and last fourteen days of pregnancy on neurons of the rat coeliac-superior mesenteric ganglion has been investigated in neonates and in adult animals. The parameters studied were neuron diameter and the level of neuronal noradrenaline fluorescence. The morphology was more permanently affected by fourteen than by seven days undernutrition as shown by the smaller neuron diameters persisting at six months. Both periods of undernutrition affected noradrenaline levels permanently: seven days undernutrition producing a rise and fourteen days producing a depression. These changes demonstrate the permanent effects of maternal undernutrition on the development and maturation of prevertebral sympathetic neurons.

Animals

Age related heterogeneity of lipopigments in human sympathetic ganglia.

The histochemical, autofluorescence and morphological characteristics of lipopigments accumulating with age in the human sympathetic neurons were studied. The spectral characteristics of the lipopigment autofluorescence change with age suggesting the accumulation of additional components in the residual bodies. This component is electron microscopically highly osmiophilic and stains also with silver staining. These changes may indicate the gradual melanization of the lipopigments due to auto-oxidation of catecholamines. The accumulation of the melanized form of lipopigment may be a sign of more advanced cellular trauma.

Adolescent

Arterial supply of the rat superior cervical ganglion: a morphological and semiquantitative histochemical investigation.

A combination of morphological and semiquantitative techniques has been employed to characterise the arterial supply to the rat superior cervical ganglion. Microfil and ink-injected preparations indicate that the major supply is from the carotid body artery which sends several branches to the rostral part of the ganglion and a recurrent branch to its caudal part. Occlusion of the proximal part of the external carotid artery, and hence the carotid body artery (whether it be derived from the external carotid or occipital artery), produces a dramatic reduction in neuronal succinate dehydrogenase activity within 30 minutes. In contrast, section of the preganglionic trunk and vagus nerves--whose vascular beds are seen to anastomose with that of the superior cervical ganglion--results in no observable change in ganglion activity. It is concluded that the carotid body artery is the only significant artery of supply to the rat superior cervical ganglion and therefore that preganglionic neurectomies can be carried out without risk of anoxia to the neurons of the ganglion.

Animals

Long-lasting effects of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on prevertebral sympathetic neurones in the rat.

Following intraperitoneal administration of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) in rats, the irides and pieces of jejunum were treated by the glyoxylic acid method in order to reveal their adrenergic nerves. Seven days after the injection, the fluorescence of adrenergic nerves in the iris was partly restored and by 35 days was indistinguishable in density and brightness from controls. In contrast, even 118 days post-injection, the adrenergic component of Auerbach's plexus of the jejunum was still markedly affected by the DSP-4. The regeneration was incomplete, giving a patchy appearance, and less fluorescent than the controls. It is suggested that, when injected intraperitoneally, DSP-4 can have more potent effects than hitherto realised.

Adrenergic Fibers

Fluorescence histochemical evidence for decreased noradrenaline synthesis in sympathetic neurones of aged rats.

Measurements of formaldehyde-induced fluorescence of noradrenaline (NA) in sympathetic neuronal perikarya of aged (24-month) and younger (4-month) control rats revealed little or no NA fluorescence in many sympathetic neurones of aged rats: neuronal fluorescence in younger rats was substantially greater. Monoamine oxidase inhibition increased NA fluorescence in all rats, but the increase was greater in the 4-month controls. Reserpine administration caused an almost complete disappearance of NA fluorescence after 12 h. However, normal NA levels were restored in the 4-month controls after 48 h but not for 7 days in the aged rats.

Age Factors

Qualitative observations on fine structural changes with age in the ventricular myocardial cells of a teleost, Pleuronectes platessa L.

Ultrastructural studies on the ventricular myocardial cells of a sample of 10...16 year old plaice (Pleuronectes platessa L.) reveal an increase in the amount of glycogen particles, the presence of primary and secondary lysosomes and small intracellular vacuoles. Mitochondria were predominantly swollen and many were observed in different stages of degeneration and degradation by lysosomes within autophagic vacuoles. Myofilaments were not as distinctly defined as in the control group of 3...5 year old fish in which also the above features were not apparent. Such features are therefore interpreted as being age-associated.

Aging

Measurements of noradrenaline fluorescence in axons of chick embryo sympathetic ganglia grown in three day culture.

Chicken embryo sympathetic ganglion fragments, grown in culture for three days, were incubated for short periods in appropriate experimental and control media to provide information on axonal uptake of exogenous noradrenaline in the presence and absence of the uptake-blocking drugs, protriptyline and phenoxybenzamine. The cultures were dried, gassed in formaldehyde vapour and examined by fluorescence microscopy. Spot readings were taken on axon-bundles using a microspectrophotometer. Readings were corrected for the amount of tissue present in each field, using graticule and interferometric methods. Brightness was uniform along individual axon-bundles, but varied from bundle to bundle within the same culture. Despite this range in brightness the readings fell into a normal distribution about the mean. Dose-dependent increases in brightness were obtained following incubation with noradrenaline. A clear indication of the effect of the blocking drugs was observed but the range in brightness prevented reliable quantitative data on these effects from being obtained. It was concluded that the wide range of brightness within each culture reflected a lack of equivalence in the intrinsic noradrenaline-uptake properties of the axon-bundles developing in such cultures.

Animals