PubMed HealthSearch

Biomedical subjects

A Hervonen

Publications and source records attributed to A Hervonen.

At least 19 recordsLinked to original sources

Lifelong ethanol consumption enhances the age-related changes in rat sympathetic neurons.

The effects of aging and chronic ethanol administration on the histochemical and morphometric features of rat superior cervical ganglion were studied in a rat strain selected for voluntary alcohol consumption. Ethanol was administered to the experimental group ad libitum (10% v/v in drinking water) from 3 months to 28 months of age, the average ethanol intake being 6.4-5.4 g/kg per day. The sympathetic neurons of the ethanol consuming rats showed several signs of enhanced degeneration, e.g. decreased neuronal packing density, increased amount of age-pigment and decreased intensity of catecholamine histofluorescence and tyrosine hydroxylase immunoreactivity. The results may indicate a selective vulnerability of peripheral sympathetic neurons rather than a universal accelerated aging due to chronic ethanol exposure.

Aging

Effect of sialectomy on the superior cervical ganglion sympathetic neurons in young adult and aged mice.

The dependence of superior cervical ganglion (SCG) adrenergic neurons on their target organ submandibular salivary gland containing high concentrations of nerve growth factor was studied in adult and aged male mice. The submandibular salivary glands were removed (sialectomy) either uni- or bilaterally, and the SCG were studied by fluorescence microscopy and histochemically. Catecholamine fluorescence and tyrosine hydroxylase immunoreactivity decreased after sialectomy, suggesting reduced noradrenaline production. Neuronal density was lower in the aged controls than in the young controls. In both age groups, sialectomy reduced the density of catecholamine-producing neurons. In the mouse SCG, there was remarkable heterogeneity in the size of neuronal somata. In aged control mice there was a greater number of large-size neurons than in young adult control mice. Six weeks postoperatively, no large catecholamine-producing neurons could be observed in the ganglia. Yellow autofluorescent lipopigments accumulated with age in the adrenergic neurons. Sialectomy increased the accumulation of lipopigments in both young and aged neurons. Sialectomy resulted in (a) reduced catecholamine fluorescence, (b) reduced tyrosine hydroxylase immunoreactivity, (c) reduced number of catecholamine neurons, (d) increased autofluorescent lipopigment. Ageing resulted in (a) reduced number of neurons, (b) increased ratio of large to small neurons, (c) increased autofluorescent lipopigment. Alterations after sialectomy were more detrimental in the aged ganglia than in the young adult ganglia. The discontinuation of the retrograde supply of nerve growth factor may contribute to these alterations.

Aging

Interaction of aging and lifelong ethanol ingestion on ethanol-related behaviors and longevity.

The interactions of aging and long-term voluntary ethanol consumption were studied in the alcohol-preferring AA (Alko Alcohol) rats. The mean daily ethanol intake was 6.45 +/- 0.31 g/kg/day (mean +/- SE) at the beginning of the exposure at 3 months of age. The control animals were given only food and water ad libitum. There was no difference in survival or weight gain between the control and ethanol groups. When tested for voluntary ethanol intake at the age of 24 months, the rats in the ethanol group consumed significantly more ethanol than the controls. The two groups did not differ in ethanol-induced motor impairment, sleep-time, or hypothermia, nor in the rate of ethanol elimination. The 24-month-old animals, however, showed higher sensitivity to ethanol than the 3-4-month-old rats in the sleep-time test. It is concluded that the feeding regimen used in this study did not produce any detectable interactions between ethanol and the aging processes in the AA rats.

Aging

Light and electron microscopic features of peripheral ganglion cells cultured from young and aged Wistar rats.

Neurons of the dorsal root ganglion (DRG) and sympathetic superior cervical ganglion (SCG) were cultured as explants from young adult (3 months old) and aged (28 months old) Wistar rats. Both aged DRG and SCG neurons showed delayed neurite outgrowth compared to young adult neurons. Young and some aged cultured neurons had an ultrastructure similar to that found in normal uncultured cells, but most of the aged cultured neurons displayed a heavy accumulation of homogenous lipid-like inclusions in addition to classic age pigments. Occasionally, large neurofilament aggregates were seen in aged DRG neurons. They were sometimes localized perinuclearly, resembling neurofibrillary tangles. The results show that even very old peripheral neurons survive in culture. As aged cultured neurons show degenerative changes not observed in young adult neurons, it is suggested that cultured peripheral neurons of different ages could provide useful means for neuronal aging studies.

Aging

The localization of the beta-subtype of protein kinase C (PKC-beta) in rat sympathetic neurons.

The localization of PKC-beta was studied in rat sympathetic neurons using a polyclonal antibody specific for the beta 1- and beta 2-subspecies. The tissues studied included the superior cervical (SCG) and hypogastric (HGG) ganglia and the target tissues of the SCG and HGG neurons: the submandibular gland, iris, prostate and vas deferens. PKC-beta-LI was found in nerve fibers in both ganglia. A proportion of the fibers in the SCG disappeared after decentralization, suggesting that the fibers were of both pre- and postganglionic origin. The somata of the HGG and SCG neurons expressed varying amounts of PKC-beta-LI, the majority of SCG neurons being labelled only after colchicine treatment. In all target tissues there were PKC-beta-immunoreactive nerve fibers in bundles, but the most peripheral branches of the fibers were negatively labelled. The results show that PKC-beta-LI is widely present in sympathetic postganglionic neurons with mainly quantitative differences. The lack of PKC-beta in the most peripheral branches of nerve fibers might be a general feature of sympathetic postganglionic neurons, suggesting that the participation of PKC-beta in neurotransmitter release and in other functions in nerve terminals in sympathetic adrenergic neurons is unlikely.

Animals

Histochemistry of sympathetic neurons allotransplanted from young and aged mice to the submandibular gland.

Sympathetic ganglion tissue of young (3 months) and aged (24 months) NMRI mice was allotransplanted into the submandibular gland to study the influence of aging on the survival of grafted neurons. The submandibular gland (SMG) was chosen as a host tissue because of its high concentration of NGF and good blood supply. Four weeks postgrafting the viability of transplants was evaluated using the formaldehyde-induced fluorescence technique, tyrosine hydroxylase (TH) immunohistochemistry, and morphometry. The density of neurons, catecholamine fluorescence and TH immunoreactivity (TH-IR) appeared to be almost unchanged when the transplant was completely surrounded by the SMG tissue, whereas transplants located within the interlobular septum and capsule, or even outside the capsule, showed significantly reduced neuronal survival. The shape of most of the transplanted neurons was not different from those in the intact ganglia. The average diameter of the transplanted young neurons was significantly decreased; this was not the case with the aged neurons. The histograms of grouped diameter values showed a shift to smaller cells in ganglion transplants in both age groups. The transplants in mice treated with 6-OH-dopamine showed considerable regrowth of adrenergic nerve fibers. There seemed to be no marked difference in the survival of transplanted neurons between aged and young animals. The results indicate that the sympathetic neurons from both young adult and aged animals survive the allotransplantation procedure. The neurotrophic factors together with dense vascularization present in the mouse submandibular gland may be beneficial for the restoration of the integrity of mature and aged adrenergic neurons.

Aging

Histochemically demonstrable catecholamines in the sympathetic nervous system of trisomic 16 and normal fetal mice.

The formaldehyde-induced fluorescence (FIF) and micro-spectrofluorometric techniques were used to study catecholamines in the sympathetic nervous system of normal and trisomy 16 fetal mice with a gestation age of 15 days, an animal model for human trisomy 21 (Down's syndrome). FIF intensity in the stellate sympathetic ganglion of trisomic embryos did not differ from that of controls, whereas in the adrenal medulla the FIF intensity was 38% less in trisomic than in control embryos. When adrenal medullary cells from embryos with a gestational age of 15 days were maintained in culture for 7-10 days, a difference in FIF intensity between groups was still evident. The rate of noradrenaline uptake in cultured adrenal medullary cells also was significantly less in trisomic than in control fetal mice. The results suggest that the development of adrenal medulla is slowed in trisomic 16 mice and that uptake of noradrenaline by trisomic adrenal medullary cells is impaired.

Adrenal Medulla

Responses of cortical cerebral blood flow produced by stimulation of cervical sympathetic trunks are well maintained in aged rats.

Responses of cortical cerebral blood flow (CBF) in the parietal cortex following electrical stimulation of cervical sympathetic trunks (CSTs) were compared in healthy adult (4-6 months old) and healthy aged (28-32 months old) Fischer-344 rats anesthetized with urethane. The cortical CBF was continuously monitored using laser Doppler flowmetry (LDF). The electrical stimulation of CSTs with supramaximum intensity caused the frequency-dependent initial-increase and late-decrease responses of cortical CBF in both adult and aged rats. There were no significant differences in magnitude and time course of the responses of the cortical CBF with the comparable frequencies of the electrical stimulation of the CSTs between the adult and the aged rats. These evidences suggest that the neural control of the cortical CBF by the sympathetic nerves is quite well maintained in aged rats.

Aging

Viability of adrenal chromaffin cells in the superior cervical ganglion of young adult and aged rats.

Adrenal medullary tissue was autotransplanted to the superior cervical ganglion (SCG) of aged (26 months old) and young adult (3 months old) rats. Four and 20 weeks after operation, the viability of the transplants was evaluated using the formaldehyde-induced fluorescence (FIF) technique and tyrosine hydroxylase (TH) immunocytochemistry. Four weeks postgrafting, the transplant consisted of a densely-packed group of intensively fluorescent chromaffin cells in both age groups. The cells showed strong TH immunoreactivity and some of them were elongated, but only a few displayed short processes. At 20 weeks, most of the cells were spindle shaped and sent out fluorescent processes and a few of them were transformed toward ganglion-like cells. The results suggest that both young and old adrenal chromaffin cells are able to survive, produce neuronal processes and transform toward a neuronal phenotype in the rat superior cervical ganglion.

Adrenal Medulla

Administration of adrenocorticotropic hormone (ACTH) enhances Fos expression in the rat adrenal cortex.

The effect of ACTH on the expression of Fos in rat adrenal glands was investigated immunocytochemically at both light and electron microscopic levels. An approximately 4-fold increase in the number of Fos-positive cortical cells per unit area of the adrenal cortex was found 45 min following a single injection of ACTH (i.v., 2 IU/kg b.w.), as compared with the control animals. The number of immunoreactive cells reached a maximum 90 min after ACTH injection and remained high 150 min after the injection. However, 5 h following the injection it declined significantly. At the ultrastructural level, the ACTH-induced Fos-like immunoreactivity was localized in the nuclei of cortical cells, exclusively confined to the nuclear regions associated with the euchromatin. The result that ACTH enhances Fos-like immunoreactivity suggests that ACTH is involved in c-fos induction in adrenal cortical cells. The characteristic intracellular localization of Fos-like immunoreactivity implies that Fos, once synthesized, may be rapidly translocated into the nuclei of the cells, where it participates in transcriptional regulation of genetic events.

Adrenal Cortex

Immunohistochemical detection of c-fos proteins in cultured human glial cells--induction by cyclic AMP and phorbol ester.

The expression of c-fos protein in cultured human glial cells derived from the brain and spinal cord was investigated immunocytochemically. Primary cultures of fetal glial cells were maintained in culture for three weeks and deprived of animal sera for 22 h. The glial cell nature of the cells was ascertained by GFAP-immunoreactivity. Incubations with phorbol dibutyrate, 8-Br-cAMP and sodium nitroprusside representing signal transduction pathways of PKC, PKA and cyclic GMP kinase, respectively, were carried out for 60 and 120 min. The control serum-deprived cultures did not display c-fos protein immunoreactivity (c-fos-IR), whereas phorbol dibutyrate incubation for 120 min induced strong c-fos-IR in the nuclei of both brain and spinal cord derived glial cells. Semiquantitative intensity measurements revealed a slight c-fos-IR induction after 8-Br-cAMP as well, but not after sodium nitroprusside. The observations suggest that c-fos protein is involved in PKC and PKA signal transduction in cultured human glial cells.

8-Bromo Cyclic Adenosine Monophosphate

Survival of both young and aged sympathetic neurons in the adrenal cortex after autotransplantation.

Sympathetic ganglion tissue of 3-months- and 18-months-old Fischer-344 rats was autotransplanted into the adrenal gland in order to determine the effect of aging on the survival of grafted neurons. Adrenal cortex was chosen as the host tissue because it is well vascularized and has a high concentration of glucocorticoids, which stimulate the synthesis of catecholamines. At 4 weeks following the transplantation, the density of neurons was decreased in all transplants, but approximately the same proportion of remaining neurons showed tyrosine hydroxylase immunoreactivity as in intact ganglia. At 8 weeks, a subpopulation of large neurons showed an increased accumulation of age pigment. The heavily pigmented neurons were usually devoid of catecholamines, whereas small non-pigmented neurons frequently showed strong catecholamine histofluorescence and tyrosine hydroxylase immunoreactivity. There was no marked difference between old and young animals in the survival of transplanted neurons. The results show that the sympathetic neurons from both 3-months-and 18-months-old animals survived the autotransplantation procedure. The humoral environment of the adrenal cortex may be beneficial for the restoration of the integrity of sympathetic neurons.

Adrenal Cortex

Effect of vitamin E and selenium supplement on the aging peripheral neurons of the male Sprague-Dawley rat.

The effect of life-long diets containing different concentrations of selenium and vitamin E on the age pigment accumulation in the rat superior cervical ganglion, vagal ganglion and dorsal root ganglion, was studied using microspectrofluorometry. All types of ganglia showed unchanged amounts of age pigments at low or high concentrations of selenium, whereas dietary concentration of vitamin E regulated age pigment content in the dorsal root ganglion, but not in the superior cervical and vagal ganglion. Vitamin E deficiency induced a three-fold increase in age pigment content in dorsal root ganglion at 8 months of age, whereas high vitamin E concentration was associated with a lesser amount of pigments at 18 months of age. Emission spectra of age pigment recorded from the dorsal root ganglion and vagal ganglion were different from that from the superior cervical ganglion, but were independent of dietary concentrations of selenium or vitamin E. The results suggest that exogenous antioxidants may play a more crucial role in lipid peroxidation and accumulation of age pigment in dorsal root ganglion than in autonomic ganglia.

Administration, Oral

Localization of protein kinase C-beta-like immunoreactivity in the rat dorsal root ganglion.

The localization of protein kinase C-beta-like immunoreactivity (PKC-beta-LI) was studied in the rat dorsal root ganglion (DRG) using an antibody specific for a peptide sequence common to the beta 1- and beta 2-subtypes. PKC-beta-LI was seen in 45% of neuronal cell bodies and in nerve fibers, which were mostly myelinated. The PKC-beta-LI-containing cell bodies had a diameter significantly larger than the unlabeled cell bodies. The results suggest that PKC-beta is a PKC subtype involved in cell surface signal transduction in the subpopulation of large DRG neurons.

Animals

Neuronal degeneration and lipopigment formation in rat sympathetic ganglion after treatment with high-dose guanethidine.

Degenerative changes in the rat superior cervical ganglion (SCG) were studied 3 months after treatment with a high-dose of guanethidine using microspectrofluorometry and electron microscopy. The density of the SCG neurons was decreased by 30% and by 60% following 1 and 2 weeks treatment respectively with guanethidine. Intraneuronal lipopigments were increased after the treatment, whereas cytoplasmic catecholamines were decreased. Electron microscopy revealed swollen mitochondria and a novel type of lipo-pigment in surviving neurons. The number and structure of small intensely fluorescent (SIF) cells remained unchanged after the treatment. The results suggest that accelerated lipid peroxidation processes might be involved in guanethidine neurotoxicity and that intraneuronal concentrations of catecholamines may be related to this toxicity.

Animals

Organizational role of testosterone on the biochemical and morphological development of the hypogastric ganglion.

Previous reports have demonstrated that after postnatal day 10 testosterone influences hypogastric ganglion (HG) development by 'activating' morphological and biochemical indices. We now report an 'organizational' influence on the developing HG during the first 10 postnatal days. To investigate the organizational effects of testosterone, male rats were castrated within 12 h of birth. Testosterone replacement therapy initiated following castration maintained the normal number of neurons in the HG. Conversely, delayed replacement therapy starting at day 10 or vehicle treatment only, resulted in a significant decrease in neuron number. Castration also produced a significant decrease in somal and nuclear cross-sectional areas. Testosterone replacement, whether initiated immediately or if delayed until day 10, restored somal and nuclear cross-sectional areas to normal. Tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) activities were sensitive to both testosterone dosage and the time of administration. Testosterone decanoate administered subsequent to castration was not able to completely reverse the enzyme activity deficits, while delayed replacement therapy was even less effective in restoring enzyme activities. In contrast, higher doses of testosterone completely reversed enzyme activity deficits, and in fact produced a significant increase in TH activity. Again, delayed testosterone replacement did not fully restore deficits in enzyme activity. In summary, the hormonal environment during the first 10 days of life is critical for the organization of HG cell number; in contrast, nuclear and cell size appear to be dependent on testosterone for activation. TH and ChAT activities also appear to be organized during this dose- and time-dependent developmental period.

Adrenergic Fibers