Biomedical subjects

A Cintra

Publications and source records attributed to A Cintra.

At least 19 recordsLinked to original sources

PubMed2000

Gluco- and mineralocorticoid receptor-mediated regulation of neurotrophic factor gene expression in the dorsal hippocampus and the neocortex of the rat.

Gluco- and mineralocorticoid receptors (GR and MR) act via common promoter elements but may exert different effects on gene regulation in various regions of the forebrain. In order to separately analyse the role of GR and MR in the regulation of neurotrophic factor genes and their receptors, we used adrenalectomy and subsequent hormone injections in the rat as a model system. Twenty-four hours after adrenalectomy rats were injected with a single dose of corticosterone (2 and 10 mg/kg), aldosterone (0.5 mg/kg) or the synthetic glucocorticoid agonist RU 28362 (4 mg/kg). Gene expression of basic fibroblast growth factor (bFGF) and its high-affinity receptors [fibroblast growth factor receptor subtypes 1-3 (FGF-R1, FGF-R2, FGF-R3)], as well as brain-derived growth factor (BDNF) and neurotrophin-3 (NT-3) was analysed at 4 h after the hormone injection in CA1-CA4 (cornus of Ammon areas of the hippocampus) and dentate gyrus of the dorsal hippocampus and in neocortex by means of in situ hybridization. We found that bFGF is regulated in CA2, CA3 and dentate gyrus by GR and MR together, and in CA1, CA4 and neocortex by GR alone. FGF-R2 expression in the hippocampus seems to be regulated only by MR, while BDNF expression appears to depend on both receptors. FGF-R1, FGF-R3 and NT-3 were only moderately affected by the hormone activation of GR and MR acting in concert or alone in the various regions. Thus, the present findings suggest that the adrenal cortical system through GR and MR participate in the control of neurotrophic factor signalling in a highly subregion- and cellular-dependent manner.

Adrenalectomy↗

PubMed1999

A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse.

The effect of an acute administration of the vigilance-promoting drug modafinil ((+/-)(diphenyl-methyl)-sulfinyl-2 acetamide; Modiodal) on the nigrostriatal dopamine system was studied after damage induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by means of immunohistochemistry for tyrosine hydroxylase (TH) and a stereological method. MPTP (40 mg/kg) reduced from 24,380 +/- 902 to 13,501 +/- 522 and from 37,868 +/- 3300 to 20,568 +/- 1270, respectively, the number of TH immunoreactive (IR) and non-TH IR nigral neurons. Co-administration of Modafinil restored to normal the number of these neuronal populations. MPTP treatment induced also a reduction in the volume of TH IR neurons, which was counteracted by Modafinil administration. The data provide morphological evidence, based on unbiased stereological analysis, for a potential neuroprotective role of Modafinil, not only in dopaminergic neurons, but also with a similar magnitude in the non-DA nerve cell population of the substantia nigra after MPTP lesion. These results suggest that Modafinil has a neuroprotective role in the substantia nigra via a still undefined mechanism in which a crucial role of DA uptake blockade should be excluded. Modafinil may therefore have a therapeutic potential in neurodegenerative processes such as those occurring in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1999

Subchronic toluene exposure in low concentrations produces signs of reduced dysfunction in the 6-hydroxydopamine lesioned nigrostriatal dopaminergic system of the rat.

The effect of a subchronic (4-week) exposure to low concentrations of toluene (40 or 80 parts per million, ppm) on the brain dopaminergic system has been examined in a rat model of Parkinson's disease. A unilateral lesion of the substantia nigra (SN) dopamine (DA) nerve cells was performed by injection of a low dose of 6-hydroxydopamine (6-OH DA). The peak activity of contralateral rotational behavior induced by apomorphine was significantly decreased after exposure to 80 ppm toluene. Analysis of the neostriatum and SN ipsilateral to the lesion revealed that toluene (80 ppm, but not 40 ppm) counteracted the 6-OH DA-induced reductions of DA tissue levels both within the SN and the neostriatum. Also the lesion-induced reduction of immunoreactivity for tyrosine hydroxylase (TH IR) in the neostriatum was partly counteracted by the toluene exposure (80 ppm). In conclusion, a subchronic exposure to low doses of toluene (80 ppm) leads to signs of reduced dysfunction of the nigrostriatal dopaminergic system after the neurotoxic treatment.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats.

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR- has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.

Amino Acid Sequence↗

PubMed1997

Pancreatic beta cells are important targets for the diabetogenic effects of glucocorticoids.

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate that possible role of glucocorticoids in beta cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their beta cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic beta cell as an important target for the diabetogenic action of glucocorticoids.

Animals↗

PubMed1997

Increased potency of neuropeptide Y to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat.

The regulation by neuropeptide Y of alpha2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the alpha2A-adrenoceptor messenger RNA levels and the B(max) value of the alpha2-adrenoceptor agonist [3H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K(d) value of [3H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1-36) to antagonistically modulate alpha2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of alpha2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the alpha2A-adrenoceptor messenger RNA levels and the alpha2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1-36) to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1996

Subacute toluene exposure increases DA dysfunction in the 6-OH dopamine lesioned nigrostriatal dopaminergic system of the rat.

The potential neurotoxicity of the solvent toluene to the nigrostriatal dopaminergic system was assessed in a rat model of Parkinson's disease. Rats, 1 day after a unilateral injection of 6-hydroxydopamine (6-OH DA) into the substantia nigra, inhaled air or different concentrations of toluene (80, 300 or 1000 ppm), 6 h/day for 3 days. The animals were sacrificed 2 days after the last exposure and biochemical measurements of catecholamines and 3,4-dihydroxyphenylacetic acid (DOPAC) were performed in the neostriatum and substantia nigra. Toluene at 80 and 1000 ppm significantly enhanced the depletion of striatal DOPAC levels induced by the lesion and produced at 80 and 300 ppm a trend for intensifying the 6-OH DA-induced depletion of striatal DA stores. The alterations induced after the combined challenge to the dopaminergic nigrostriatal system may reflect endangering actions of toluene.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

On the role of glucocorticoid receptors in brain plasticity.

1. The mapping of glucocorticoid receptors (GR) in the rat central nervous system (CNS) has demonstrated their widespread presence in large numbers of nerve and glial cell populations also outside the classical stress regions. 2. The present paper summarizes the evidence that glucocorticoids via GR in the CNS can act as lifelong organizing signals from development to aging. The following examples are given. (a) In the prepubertal and adult offspring, prenatal corticosterone treatment can produce long-lasting changes in striatal dopaminergic communication. (b) In adulthood, the evidence suggests complex regulation by adrenocortical hormones of neurotrophic factors and their receptors in the hippocampal formation. (c) In aging, the strongly GR-immunoreactive pyramidal cell layer of the CA1 hippocampal area appears to be preferentially vulnerable to neurotoxic actions of glucocorticoids, especially in some rat strains. 3. Strong evidence suggests that each nerve cell in the CNS is supported by a trophic unit, consisting of other nerve cells and glial cells, blood vessels, and extracellular matrix molecules. Due to multiple actions on nerve and glial cell populations of the different trophic units, the glucocorticoids may exert either an overall trophic or a neurotoxic action. It seems likely that with increasing age, the endangering actions of glucocorticoids on nerve cells prevail over the neurotrophic ones, leading to reduced nerve cell survival in some trophic units.

Adrenal Cortex Hormones↗

PubMed1996

Localization of neuropeptide Y Y1 receptor-like immunoreactivity in catecholaminergic neurons of the rat medulla oblongata.

Neuropeptide Y receptors in the medulla oblongata participate in central cardiovascular control. The neuropeptide Y1 receptor subtype gene and amino acid sequence have been identified by molecular cloning studies. In this study, a C-terminal peptide representing amino acids 355-382 of the neuropeptide Y1 receptor was synthesized and cross-linked to thyroglobulin to produce an antibody against a partial sequence of the neuropeptide Y1 receptor, used to localize neuropeptide Y1 receptor-like immunoreactivity in the catecholaminergic neurons of the medulla oblongata. The double colour immunofluorescence technique with a polyclonal antibody against the neuropeptide Y1 receptor and a monoclonal antibody against tyrosine hydroxylase revealed that in the rat medulla oblongata, a weak (the C3 cell group) to moderately intense (the A1, A2, C1 and C2 cell groups), diffuse cytoplasmic neuropeptide Y1 receptor-like immunoreactivity was distributed primarily in the noradrenergic and adrenergic cell bodies and occasionally seen in the noradrenergic and adrenergic cell processes. Almost all tyrosine hydroxylase-like immunoreactive cell bodies in the A1, A2, C1, C2 and C3 cell groups showed neuropeptide Y1 receptor-like immunoreactivity. The neuropeptide Y1 receptor-like immunoreactivity in the A2 cell group was somewhat stronger. The present findings show localization of specific neuropeptide Y1 receptor-like immunoreactivity in the vast majority of the noradrenergic and adrenergic cell bodies of the A1, A2, C1, C2 and C3 cell groups, which are putative cardiovascular regions. The results support the view that neuropeptide Y1 receptors in the medulla oblongata are involved in central cardiovascular control and may coexist with another important receptor, the alpha 2A-adrenoceptor, also involved in central, cardiovascular regulation, since the alpha 2A-adrenoceptor-like immunoreactivity has been shown to exist in almost all noradrenergic and adrenergic cell bodies in the brainstem. In conclusion, centrally administered neuropeptide Y may act in part via neuropeptide Y1 receptors located on the soma and dendrites of noradrenergic and adrenergic neurons, where it may interact with alpha 2-adrenoceptors at least in the noradrenergic A2 neurons. This noradrenaline system may be involved in at least part of the vasodepressor actions of neuropeptide Y, noradrenaline and adrenaline in the nucleus tractus solitarii in view of the present findings.

Animals↗

PubMed1995

Neurotensin-like immunoreactivity in odontoblasts and their processes in rat maxillary molar teeth and the effect of pulpotomy.

A strong neurotensin-like immunoreactivity (NT-like IR) was detected in the odontoblast cells of the rat teeth. 4 h after a partial pulpotomy performed in two maxillary molar teeth a decreased NT-like IR was observed in the odontoblast layer located at the vicinity of the lesion together with edema and nuclear pyknosis. NT-like IR became further decreased after 24 h. After 7 days NT-like IR had almost fully disappeared with signs of necrosis of the dental pulp and infiltration of polymorphonuclear lymphocytes. It seems possible that NT like peptides in the odontoblast cell layer may play a role, e.g., in dentinogenesis and/or nociception.

Animals↗

PubMed1995

Counteraction of NYP-induced c-Fos expression in the nucleus tractus solitarii by alpha 2 receptor agonists.

Neuronal c-Fos protein-like immunoreactivity (c-Fos IR) in parts of the nucleus tractus solitarii (NTS)-dorsal motor nucleus of the vagus nerve (dmnX) complex of the anaesthetized rat was studied 90 min after NTS microinjections of neuropeptide Y (NPY) and/or adrenergic receptor agonists in relevant cardiovascular doses. Microinjections of NPY and l-adrenaline alone into the NTS induced neuronal c-Fos IR in parts of the NTS-dmnX complex, while clonidine had no action. No double-labelled GFAP/c-Fos immunoreactive cells were found in the NTS-dmnX complex after the microinjection of NPY into the NTS. Coinjections of NPY and l-adrenaline or clonidine into the NTS reduced the NPY-induced increase in c-Fos IR. The results emphasize that during cardiovascular regulation NPY receptors can control neuronal gene expression in the NTS-dmnX complex via c-fos and that stimulation of alpha 2-adrenoceptors can attenuate NPY receptor transduction also in terms of induction of c-Fos IR in the NTS-dmnX complex via an antagonistic alpha 2/NPY receptor interaction.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1994

On the plasticity of the cerebellar renin-angiotensin system: localization of components and effects of mechanical perturbation.

This study focuses on the renin-angiotensin system (RAS) in the cerebellar cortex and changes within this system after mechanically induced cerebellar injury. Using radioactive and non-radioactive in situ hybridization and immunocytochemistry angiotensinogen mRNA, angiotensinogen, angiotensin II and, for the first time, N-terminal angiotensin fragment (1-7) immunoreactivities, respectively, were demonstrated in the rat cerebellum. Angiotensinogen mRNA and angiotensinogen immunoreactivity (IR) were both present in glial cell populations of all layers, especially in the Purkinje and granular cell layers and within the cerebellar nuclei. Angiotensin II IR was demonstrated in glial cell populations in all layers using a monoclonal angiotensin II antibody, while with a polyclonal angiotensin II antiserum (Denise) some Purkinje cell bodies were labelled. After lesioning the cerebellar cortex mechanically by an injection cannula a strong increase in angiotensinogen gene expression as well as in angiotensin II and angiotensin (1-7) immunoreactivities were observed in the glial cell populations. Furthermore, putative Bergmann glial processes, as indicated from the morphological appearance became strongly angiotensin II and angiotensinogen immunoreactive in the region close to the mechanically induced lesion. It could inter alia be demonstrated for the first time using confocal laser microscopy of ANG II IR and GFAP IR that ANG II in vivo in the intact cerebellar cortex is present in astroglial processes in the molecular layer and presumably secreted into the extracellular space in form of small spheric bodies and/or taken up by other cell types. In contrast, the N-terminal fragment angiotensin (1-7) IR was restricted to the glial cell populations and appeared only after the lesion event. Thus, it is suggested that the cerebellar RAS shows marked changes in response to mechanically induced lesions. The expression of angiotensinogen as well as the production of angiotensinogen IR and angiotensin II like IR is even after mechanical lesion restricted to astrocytes, i.e., cerebellar astrocytes and putative Bergmann glial cells, and in case of immunoreactivities it spreads to the radially oriented Bergmann glial processes in the molecular layer.

Angiotensin I↗

PubMed1994

Glial and neuronal glucocorticoid receptor immunoreactive cell populations in developing, adult, and aging brain.

A detailed mapping of glucocorticoid receptor (GR) immunoreactivity (IR) in rat CNS was performed employing a mouse monoclonal antibody against rat liver GR. Subjective comparisons were made between the present results and the available data in the literature. A semiquantitation of GR immunostaining was found necessary and was obtained by microdensitometric and morphometric techniques, which enabled the distinction of neuronal and glial cell populations containing GR IR in various CNS regions. GR IR in the CNS was mainly found in the nuclear compartment. The GR was present in neuronal populations with classical neurotransmitters, especially monoamines and glutamate and with various neuropeptides. The degree of colocalization varied according to the function of the brain area. Functional implications were made in relation to stress sensitivity, mood and nociception/antinociception. The global control of networks by glucocorticoids may allow an optimal integration of different types of circuits. The GR is found already in the fetal rat and the development of GR mRNA and receptor protein was followed during the pre- and postnatal periods. The GR appears to be a major factor in brain maturation and in modulation of stress responses. In aged Brown Norway rat brain GR IR but not mineralocorticoid receptor (MR) IR is reduced in the hippocampal nerve cells. The intensity of GR IR but not the number of nerve cells is altered, indicating a reduced activation of the GR in aging in this rat strain. Overall GR participates in neuronal plasticity from fetal and postnatal life to adult life and aging.

Aging↗

PubMed1994

Adrenalectomy increases the number of substance P and somatostatin immunoreactive nerve cells in the rat lumbar dorsal root ganglia.

Using an immunocytochemical technique we have analyzed changes in substance P, somatostatin, calcitonin gene-related peptide, and galanin immunoreactivity pattern in the rat dorsal root ganglia. After 7 days of adrenalectomy, sham operated rats were compared with adrenalectomized animals either receiving a daily intraperitoneal injection of 10 mg/kg b.wt. corticosterone or vehicle. Three lumbar ganglia from each animal were blocked, serially cut, and immunostained for each neuropeptide by means of the biotin-avidin-peroxidase technique. A systematic sampling of immunoreactive ganglion cells was performed and the sample number of immunoreactive ganglion cells was calculated. After adrenalectomy, the number of substance P and somatostatin immunoreactive ganglion cells markedly increased ((means +/- S.E.M.): 245 +/- 68 versus 123 +/- 12 for sham operated animals, P < 0.01 (substance P) and 42 +/- 8 as compared to 22 +/- 9 for sham operated animals, P < 0.01 (somatostatin)). No significant changes were found in the number of calcitonin gene-related peptide and galanin immunoreactive cells after adrenalectomy. These results suggest that adrenal steroid hormones may reduce the synthesis of both substance P and somatostatin in the dorsal root ganglion cells. Daily treatment with a high dose of corticosterone, mimicking its serum levels after stress, failed to prevent the increase of peptide contents after adrenalectomy. These observations also indicate that a tonic action of corticosterone on mineralocorticoid receptors may be crucial for peptide regulation in the spinal ganglia. These results may be of relevance to adrenalectomy induced changes in sensory mechanisms, neurogenic inflammation and pain transmission and to a role of substance P and somatostatin in these processes.

Adrenalectomy↗

PubMed1994

Subpopulations of primary sensory neurons show coexistence of neuropeptides and glucocorticoid receptors in the rat spinal and trigeminal ganglia.

The coexistence of the neuropeptides substance P, calcitonin gene-related peptide, galanin, somatostatin and neuropeptide Y with glucocorticoid receptors was studied in neurons of the rat lumbar dorsal root and trigeminal ganglia by means of the double immunofluorescence technique. Based on analysis of microphotographs, about one-third of the populations of nerve cells (small and large) containing substance P or calcitonin gene-related peptide immunoreactivity (IR) showed nuclear glucocorticoid receptor IR. A similar pattern was observed within the dorsal root and trigeminal ganglia. Furthermore, within the lumbar dorsal root ganglia 50% of the small neurons, containing galanin IR, possessed nuclear glucocorticoid receptor IR of moderate intensity. Glucocorticoid receptor IR was not observed in the galanin immunoreactive neurons of the trigeminal ganglion neither in the somatostatin and NPY immunoreactive neurons of both the dorsal root and the trigeminal ganglia. The results provide a chemical anatomical basis for a direct regulation by glucocorticoids of distinct populations of substance P and calcitonin gene-related peptide immunoreactive nerve cells in the lumbar spinal and trigeminal ganglia and of galanin immunoreactive nerve cells of the spinal but not of the trigeminal ganglia.

Animals↗

PubMed1994

Basic fibroblast growth factor and steroid receptors in the aging hippocampus of the brown Norway rat: immunocytochemical analysis in combination with stereology.

The effect of aging on the hippocampal formation of the male Brown Norway rat was studied by immunohistochemistry and measurements of the immunoreactive hippocampal cells using stereological techniques. The total estimated number of glucocorticoid receptor (GR) immunoreactive neurons of the CA1-CA2 area did not differ in the 3- and the 36-month-old rat. However, the intensity of the GR immunoreactivity was decreased in the aged animals. A gradual decrease of the immunoreactivity for the mineralocorticoid receptor was also observed in the CA1-CA2 area. In the stratum oriens and the stratum radiatum of the CA1-CA2 area the immunoreactivity for basic fibroblast growth factor (bFGF) present in the glia was found to be reduced [20,000 +/- 2100 (n = 6)] in the 36-month-old rat vs the 3-month-old rat [28,500 +/- 4500 (n = 4) (*P = 0.05)]. However, there was no difference in the number of glial fibrillary acidic protein immunoreactive cells of this area in these two age groups. The present findings give evidence that in the Brown Norway rat there is no loss of the neuronal population containing glucocorticoid receptors of the CA1-CA2 area during aging but suggest that aging is characterized by deficits of glially derived growth factors, such as bFGF.

Aging↗

PubMed1994

Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system.

By means of a monoclonal mouse immunoglobulin G2a antibody against the rat liver glucocorticoid receptor and the indirect immunoperoxidase technique, the distribution of glucocorticoid receptors in neuronal and glial cell populations was mapped in the central nervous system of the male rat. The mapping was complemented by computer-assisted morphometric and microdensitometric evaluation of glucocorticoid receptor immunoreactivity in many brain regions. The quantitative analysis allowed us to achieve for the first time an objective characterization of glucocorticoid receptor distribution in the CNS, thus avoiding the ambiguities of previous mapping studies based on subjective evaluations. In addition, a taxonomic analysis of central nervous system regions containing glucocorticoid receptor immunoreactivity was carried out utilizing the quantitative parameters obtained in the morphometric evaluation. Nuclei of neuronal and glial cells containing glucocorticoid receptor immunoreactivity were detected in a widespread, but still highly heterogeneous, fashion in the central nervous system, underlining the view that glucocorticoids can control a large number of central nervous system target cells via effects on gene expression. Many nerve cell populations have been shown to contain substantial amounts of nuclear glucocorticoid receptor immunoreactivity, whereas only a low density of glial cells, in both gray and white matter, show nuclear glucocorticoid receptor immunoreactivity. Thus, in most brain areas, the major target for glucocorticoids appears to be the nerve cells. Interestingly, an inverse correlation was found in the regional density of glucocorticoid receptor-immunoreactive nerve and glial cells, suggesting that glucocorticoids may influence a brain area either via glial cells or, more frequently, via nerve cells. The results on mapping highlight the impact of glucocorticoids in areas both traditionally and not traditionally involved in stress responses. The distribution of glucocorticoid receptor immunoreactivity also emphasizes a role of glucocorticoids in the regulation of the afferent regions of the basal ganglia and the cerebellar cortex, and of both afferent and efferent layers of the cerebral cortex. Glucocorticoid receptor immunoreactivity is widely distributed over the thalamus, probably leading to modulation of activity in the various thalamocortical pathways transmitting inter alia specific sensory information to the cerebral cortex. Many unspecific afferents to the cerebral cortex are potentially regulated by glucocorticoid receptors such as the noradrenaline and 5-hydroxytryptamine afferents, since their nerve cells of origin contain strong glucocorticoid receptor immunoreactivity. Eight brain regions involving sensory, motor and limbic areas were shown to have a similarity with regard to glucocorticoid receptor-immunoreactive parameters at the level of 95%. The density of glucocorticoid receptor-immunoreactive nerve cells appeared to be the main factor in determining such a very high level of similarity. Overall, our results emphasize that glucocorticoids may appropriately tune networks of different areas to obtain optimal integration and in this way improve survival of the animal under challenging conditions.

Adrenalectomy↗

PubMed1993

Colocalization of Fos- and glucocorticoid receptor-immunoreactivities is present only in a very restricted population of dorsal horn neurons of the rat spinal cord after nociceptive stimulation.

Immunocytochemical techniques were used to study the colocalization of proto-oncogene c-fos protein (Fos)-like immunoreactivity and of glucocorticoid receptor immunoreactivity in the spinal cord dorsal horn of adult male rats after nociceptive stimulation. About 5-10% of the stimulus evoked Fos-immunoreactive profiles colocalized glucocorticoid receptor immunoreactivity. The results suggest the possibility of a corticosteroid action in a small neuronal population of the dorsal horn implicated in processing nociceptive inputs.

Animals↗