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Biomedical subjects

C Stenfors

Publications and source records attributed to C Stenfors.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cholecystokinin-8 regulation of NGF concentrations in adult mouse brain through a mechanism involving CCK(A) and CCK(B) receptors.

1. Nerve growth factor (NGF), a powerful agent for the growth, differentiation and regeneration of lesioned cells of the central and peripheral nervous systems, has in recent years been indicated as a potential therapeutic agent capable of reversing the processes of cell damage in neurodegenerative events in man. Since NGF does not cross the blood-brain barrier and central NGF administration requires invasive surgical procedures, the discovery of substances modulating in vivo NGF synthesis in the brain will be extremely useful for a possible clinical use of NGF. 2. The aim of the present study to analyse if the content of NGF in the brain of adult mice can be affected by peripheral administration of cholecystokinin-8 (CCK-8), a well known neuropeptide which has stimulant actions on neurons in the brain and promotes a variety of neurobehavioural effects both in man and rodents. 3. The dose-response and time course effects of an i.p. injection of CCK-8 on the NGF concentrations in the hippocampus, cortex, hypothalamus and pituitary of adult male mice were analysed by use of a sensitive immunoenzymatic assay for NGF. The effects of pretreatment with selective CCK(A) and CCK(B) receptor antagonists and atropine on the NGF response to CCK injection were also studied. 4. The effects of CCK-8 were dose- and time-dependent and the injection of 8 nmol kg(-1) resulted in a 3 fold increase of NGF levels in the hypothalamus and pituitary, and about a 60% increase in the hippocampus. No effects were observed in the cortex. Pretreatment with a selective CCK(A) receptor antagonist blocked the CCK-induced NGF increase in the hypothalamus and pituitary. In the hippocampus the same effect was obtained with a CCK(B) receptor antagonist. Pretreatment with atropine suppressed the CCK-induced effects on NGF levels in all the brain regions examined. 5. Our results showing that i.p. injection with CCK-8 can modulate NGF levels in the brain through a mechanism which seems, in part, to be mediated via the vagal afferents, indicate that this neuropeptide may represent a useful pharmacological approach to enhance endogenous NGF levels in neuropathologies associated with a neurotrophin deficit.

Animals↗
PubMed1998

Unilateral injection of calcitonin gene-related peptide (CGRP) induces bilateral oedema formation and release of CGRP-like immunoreactivity in the rat hindpaw.

The contribution of calcitonin gene-related peptide (CGRP) to bilateral oedema formation in the rat hindpaw following an unilateral challenge with CGRP was investigated. Rats were injected into the left hindpaw with either saline, CGRP or a CGRP antagonist (CGRP8-37). All injections were given in a double blind fashion and in a volume of 100 microl. CGRP and CGRP8-37 were administered in concentrations of 75, 150 or 300 pmol. Volumes of the right and left hindpaw were measured every hour for 5 h by plethysmometry. Injection of CGRP 300 pmol into the left hindpaw resulted in a bilaterally increased hindpaw volume after 5 h as compared with the groups given saline. No changes were found in hindpaw volumes following the injection of either 75 or 150 pmol of CGRP or 75, 150 or 300 pmol of CGRP8-37 as compared with saline injection. To elucidate whether or not the bilateral oedema formation was related to a release of endogenous CGRP, microdialysis of the contralateral hindpaw was carried out, and concentrations of CGRP-like immunoreactivity (-LI) were determined by radioimmunoassay and high performance liquid chromatography. Injection of CGRP 300 pmol into the left hindpaw increased the release of CGRP-LI into the right hindpaw perfusate after 4 and 5 h. No changes in CGRP-LI were detected in the right hindpaw perfusate following challenge with saline or CGRP8-37. To study the contribution of the nervous system to the contralateral release of CGRP-LI, sciatic nerve ligated and intact sham-operated rats were used. Sciatic nerve ligation but not sham-operation on the non-injected side abolished the increased release of CGRP-LI following contralateral administration of CGRP 300 pmol. To study the spinal cord mechanisms resulting in the bilateral oedema formation following unilateral challenge with 300 pmol of CGRP, intrathecal pretreatment with either 10 nmol bicuculline (GABA(A) receptor antagonist) or 10 nmol CGRP8-37 was carried out. Bicuculline but not CGRP8-37 abolished the bilateral oedema formation induced by CGRP 300 pmol. In order to study the mechanisms by which administration of CGRP 300 pmol induces oedema, CGRP 300 pmol was administered concomitantly with either 300 pmol of CGRP8-37 (CGRP receptor antagonist), or 3 nmol of promethazine (H1 receptor antagonist), or 3 nmol of s(-)-propranolol (5-HT1 receptor antagonist), or 3 nmol of cyproheptadine (5-HT2 receptor antagonist) or 3 nmol of ICS 205-930 (5-HT3 receptor antagonist). Oedema formation was measured at 1, 5, 7 and 24 h. Injection of CGRP 300 pmol into the left hindpaw induced a bilateral oedema formation which was still significant at 24 h. Concomitant administration of either CGRP8-37, ICS 205-920 or cyproheptadine blocked the oedema formation at 24 h. No effect on oedema formation was found when CGRP 300 pmol was co-administered with either promethazine or s(-)-propranolol (H1 and 5-HT1 receptor antagonists, respectively). The results of the present study show that both the nervous system and local inflammatory processes contribute to bilateral hindpaw oedema formation following unilateral challenge with CGRP 300 pmol. Our results indicate that endogenous release of CGRP following inflammatory response may play an important role in inducing oedema formation.

Animals↗
PubMed1997

Characterization of endogenous neuropeptide Y in rat hippocampus and its metabolism by nanospray mass spectrometry.

Neuropeptide Y (NPY) is a 36-residue-long neuropeptide which has been implicated in the regulation of feeding behavior and modulation of the circadian rhythm. We identified the primary structure of the endogenous NPY-immunoreactive material in the rat hippocampus using a combination of chromatographic techniques and nanospray mass spectrometry. The major component in the brain tissue corresponded to the authentic amidated form of NPY(1-36). The fate of NPY in the central nervous system was studied by subjecting pure peptide to the protease(s) present in hippocampal synaptosomes to reveal potential cleavage site(s). NPY was efficiently metabolized with a single cleavage between Leu30-Ile31. Thus, processing of NPY resulted in formation of the C-terminally truncated fragment NPY(1-30) and its counterpart NPY(31-36). The enzyme revealed properties of aspartic protease, being blocked by pepstatin and having a pH optimum between 4 and 5. The data clarify the structure of NPY and its inactivation pathway in the brain, which is different from that found in the periphery, and may have important consequences in vivo.

Animals↗
PubMed1997

High-dose anabolic androgenic steroids modulate concentrations of nerve growth factor and expression of its low affinity receptor (p75-NGFr) in male rat brain.

The effects of treatment with a high dose of nandrolone or testosterone on nerve growth factor (NGF) levels and NGF low-affinity receptor (p75-NGFr) distribution in the brain were analyzed. Nandrolone, subcutaneously injected in rats for several weeks, caused an increase of NGF levels in the hippocampus and septum and a decrease in the hypothalamus. The number of p75-NGFr-immunoreactive neurons and the p75-NGFr expression levels were reduced in the septum and vertical and horizontal Broca's bands. Testosterone injections caused an increase of NGF levels in the hippocampus, septum, and occipital cortex and induced an upregulation of p75-NGFr in the forebrain NGF target regions. This testosterone effect suggests that nandrolone and testosterone affect brain NGF target cells by a different mechanism(s). Nandrolone may interfere with NGF transport and/or utilization by forebrain neurons, causing an altered p75-NGFr expression and NGF accumulation as a consequence. Since NGF is known to maintain forebrain neurons and to regulate neurobehavioral functions, including memory, learning, and defensive behavior, it is possible to hypothesize that this neurotrophin may play a role in the mechanism of action of anabolic androgenic steroids (AAS) in the brain and be associated with endocrine and behavioral dysfunctions occurring due to AAS abuse.

Anabolic Agents↗
PubMed1997

A comparison between microwave irradiation and decapitation: basal levels of dynorphin and enkephalin and the effect of chronic morphine treatment on dynorphin peptides.

Opioid peptides were analysed in tissue extracts of various brain structures and the pituitary gland from rats sacrificed by microwave irradiation, and compared with peptide levels in tissue extracts from decapitated rats. Dynorphin A, dynorphin B and Leu-enkephalinArg6, derived from prodynorphin, and Met-enkephalinArg6Phe7 from proenkephalin, were measured. Basal immunoreactive levels of dynorphin A and B were consistently higher in extracts from microwave-irradiated rats, whereas in these extracts immunoreactive levels of Leu-enkephalinArg6, an endogenous metabolite of dynorphin peptides, were either lower than, the same as or higher than in decapitated rats. Immunoreactive levels of Met-enkephalinArg6Phe7 were higher in microwave-irradiated rats. Effects of morphine treatment on prodynorphin peptide levels were evaluated and compared with previous findings in decapitated rats. Dynorphin immunoreactive levels were higher in the nucleus accumbens and striatum of morphine-tolerant rats than in corresponding areas in saline-treated rats. These results indicate tissue-specific metabolism of prodynorphin peptides and show that metabolism of opioid peptides occurs during the dissection procedure after decapitation of the rat even though precautions are taken to minimize degradation.

Animals↗
PubMed1997

Effects of electroconvulsive stimuli and MK-801 on neuropeptide Y, neurokinin A, and calcitonin gene-related peptide in rat brain.

Rats were pretreated with 0.9% NaCl, or 0.1 or 1.0 mg/kg MK-801, an anticonvulsant and a psychotomimetic drug, and 60 minutes later given ECS or sham ECS. After six sessions the animals were sacrificed and neuropeptide Y (NPY-), neurokinin A (NKA-), and calcitonin gene-related peptide (CGRP-) like immunoreactivity (-LI) measured with radioimmunoassays. ECS increased NPY-LI in frontal cortex, striatum, occipital cortex and hippocampus, and NKA-LI in occipital cortex and hippocampus. MK-801 increased CGRP in a dose-response manner in frontal cortex, and NKA-LI in occipital cortex. Although the higher MK-801 dose reduced seizure duration by 50%, the ECS induced NPY-LI increase in striatum, occipital cortex and hippocampus, and NKA-LI in occipital cortex was not diminished. In contrast, there was a parallel decrease in seizures and NPY-LI and NKA-LI changes in frontal cortex and hippocampus, respectively. Investigation of neuropeptides in brain may contribute to understanding of the mechanisms of action of antidepressive and antipsychotic treatments and of psychotomimetic drugs.

Analysis of Variance↗
PubMed1996

Modification of lymphoid and brain nerve growth factor levels in systemic lupus erythematosus mice.

In the present work we investigated the production of nerve growth factor (NGF) in the brain and peripheral tissues of female NZB/W F1 mice, a well characterized model of murine lupus. Our results indicate that while no significant difference in the NGF content was observed in the sera and tissues of NZB/W mice and its parental strains during the first months of life, the levels of circulating NGF and the NGF content in the kidneys significantly increase in the autoimmune mice during the development of the disease. The NGF-producing brain regions showed a decrease in NGF concentration in 8 month-old NZB/W mice. Moreover, we found a modification of the NGF concentration in the spleens of autoimmune mice at 5 and 8 months. Our data support the hypothesis of a correlation between NGF and the inflammatory state of systemic lupus erythematosus (SLE) and indicate that NGF could have a role in the pathogenesis of this disease.

Aging↗
PubMed1996

Nerve growth factor stimulates production of neuropeptide Y in human lymphocytes.

The production of neuropeptide Y (NPY) in lymphocytes obtained from human tonsils was investigated using radioimmunoassay. While unstimulated lymphocytes did not produce detectable amounts of NPY, NPY synthesis was induced after cell activation. Our results show that the addition of nerve growth factor (NGF) to unstimulated lymphocytes has an effect similar to that of mitogens, both leading to production of NPY. The study of purified B and T cells confirmed that only activated cells are able to synthesize NPY. The stimulatory effect of NGF on NPY production is not a common characteristic of all lymphocytes: only unstimulated T cells respond to NGF by synthesizing NPY. No such effects is seen in purified B cells.

B-Lymphocytes↗
PubMed1996

Effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and concentrations of neuropeptides in the hippocampus in WKY and SHR rats.

The effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and on hippocampal concentrations of neuropeptide Y, neurokinin A, substance P, galanin and vasoactive intestinal peptide (VIP)-like immunoreactivities were studied in WKY (wistar-Kyoto) and SHR (spontaneously hypertensive) rats. Significantly higher concentrations of substance P-like immunoreactivity, neurokinin A-like immunoreactivity and neuropeptide Y-like immunoreactivity were found in the hippocampus immediately after 3 weeks of treatment (electro-acupuncture and running), but not 1 week after the last (tenth) changes in neuropeptide concentrations were similar in the two rat strains. Open-field behaviour was significantly reduced during the treatment period in both strains. There were significant negative correlations between behaviour and neuropeptide concentrations in SHR rats, suggesting interdependency with sympathetic activity. It is proposed that the effects of electro-acupuncture and physical exercise in rats are related to increases in neuropeptide Y, neurokinin A and substance P in the hippocampus.

Animals↗
PubMed1995

Significant changes in neuropeptide concentrations in the brain of normotensive (WKY) and spontaneously hypertensive (SHR) rats following knee joint monoarthritis.

Changes induced by chronic monoarthritis in the nervous system was studied by measuring concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities in the brain and in the knee joints of control and monoarthritic normotensive (WKY) and spontaneously hypertensive (SHR) rats on day 21 after the induction of monoarthritis. Knee joint monoarthritis was induced by intra-articular injection of Freund's adjuvant into the right knee joint. The severity of arthritis was examined by measuring knee volumes and scratching behaviour and by X-ray. The right knee of both WKY and SHR monoarthritic rats had an increased volume and osteoporosis. SHR rats had more severe arthritis and increased scratching behaviour compared to the WKY. Tachykinins were significantly decreased in the hypothalamus of arthritic rats. In the pituitary higher concentrations of tachykinins and CGRP were found in the arthritic and/or control SHR rats than in the WKY. In the occipital cortex, striatum and hippocampus NPY was increased in monoarthritic rats. No correlation was found between neuropeptide concentrations in the brain and knee joints. Decrease of tachykinins and increase of CGRP to different degree in the hypothalamus and/or pituitary of the arthritic WKY and SHR rats indicates that these changes were selectively associated with the basal level of sympathetic tone and possibly related to the greater severity seen in SHR rats. The increase of NPY in the brain, not influenced by sympathetic tone, may be part of a general defence reaction to inflammation.

Animals↗
PubMed1995

Monosodium glutamate increases NGF and NPY concentrations in rat hypothalamus and pituitary.

The effects of MSG treatment on NGF and NPY levels were analysed in the hypothalamus, pituitary, adrenal, thyroid and testis of adult rats. Daily i.v. injections of MSG (1 g kg-1 for 1 week) induced an increase of NGF in the hypothalamus (control (C) = 378 +/- 54; saline (S) = 369 +/- 36; MSG = 479 +/- 35 pg g-1 tissue; p < 0.001) and pituitary (C = 310 +/- 34; S = 376 +/- 114; MSG = 576 +/- 98 pg g-1 tissue; p < 0.01). Hypothalamic and pituitary NPY concentrations were also altered in the MSG-treated rats. Compared with saline-treated rats, the NPY concentration increased by 43% in the hypothalamus and 37.5% in the pituitary of MSG-treated rats. No significant changes in NGF and NPY content were found in the adrenal or thyroid of treated animals. These results suggest that hypothalamic and pituitary NGF and NPY levels may be involved in the control of neuroendocrine functions that are affected by MSG treatment.

Animals↗
PubMed1995

Concurrent analysis of neuropeptides and biogenic amines in brain tissue of rats treated with electroconvulsive stimuli.

We developed a method for measuring neuropeptides and monoamines in the same rat brain tissue and applied this method to study the effects of electroconvulsive stimuli (ECS) on these compounds. Rats were treated with repeated ECS or sham ECS. After sacrifice by focused microwave irradiation, brains were dissected and immediately frozen. The tissues were extracted in acetic acid. After lyophilization the samples were reconstituted in phosphate buffer and divided in three fractions: (1) was further purified on a cation-exchange column before catecholamines were measured on a high-performance liquid chromatography (HPLC) system, (2) for measuring serotonin on the HPLC system, (3) for measuring peptide concentrations by specific radioimmunoassays. Confirming our previous findings, ECS significantly increased neuropeptide Y-like immunoreactivity (-LI) in hippocampus and frontal cortex and neurokinin A-LI in the hippocampus, while no changes in substance P- and neurotensin-LI were detected. New findings were a decrease in noradrenaline concentrations in the frontal and occipital cortex and hippocampus, an increase in dopamine concentrations in the frontal and occipital cortex and no serotonin change. In summary, we have developed methods to measure both peptides and monoamines in the same brain tissue specimens, and have shown that ECS leads to changes in both neuropeptides and classical neurotransmitters in distinct brain regions.

Animals↗
PubMed1995

Region-specific effects of chronic lithium administration on neuropeptide Y and somatostatin mRNA expression in the rat brain.

The aim of this study was to examine the effects of 4-week lithium (Li+) food supplementation on neuropeptide mRNA expression in the rat brain. In situ hybridisation was used to determine the effects on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA. Increases in NPY mRNA levels were seen in the hippocampus, layers II-III of the entorhinal cortex, nucleus accumbens shell and in the medial caudate-putamen. Increases in SS mRNA expression were seen in the layers IV-VI of the entorhinal cortex and in the lateral caudate putamen. Thus, Li+ appears to affect discrete populations of NPY and SS mRNA expressing neurons, with possible relevance to beneficial effects of Li+ in affective disorders.

Animals↗
PubMed1995

Changes of neuropeptide concentrations in the brain following experimentally induced mononeuropathy in Wistar Kyoto and spontaneously hypertensive rats.

The effect of unilateral, experimentally induced, mononeuropathy on concentrations of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP), calcitonin gene-related peptide CGRP) and galanin- (GAL-) like immunoreactivities (-LI) was studied in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rat brains. Two weeks following ligation of the sciatic nerve, significantly higher concentrations of NPY-LI were found in the hippocampus, striatum and occipital cortex of both rat strains. CGRP-LI and GAL-LI were increased in the hippocampus of WKY rats. NKA-LI and SP-LI were decreased to different degrees in the pituitary of the WKY and SHR rats, indicating that the changes of the tachykinins, CGRP and GAL were selectively associated with the basal level of sympathetic tone. The increased concentrations of NPY-LI in the brain, not influenced by sympathetic tone, may be part of a general defense reaction in response to trauma.

Animals↗
PubMed1995

Chromatographic and immunochemical characterization of rat brain neuropeptide Y-like immunoreactivity (NPY-LI) following repeated electroconvulsive stimuli.

The present work investigates the possible existence of molecular heterogeneity of endogenous neuropeptide Y (NPY) in the rat brain and, if existing, whether it is affected by repeated electroconvulsive stimuli (ECS). Different column chromatographic techniques (gel-permeation chromatography, HPLC, ion-pair reverse-phase HPLC) were used combined with immunochemical methods based on antisera directed towards two different epitopes of NPY (antiserum N1, directed towards the midportion of NPY, and antiserum C1, directed towards the C-terminal end of NPY). Following repeated ECS increased concentrations of NPY were seen in the occipital cortex and hippocampus (P < 0.001) when analyzed by direct radioimmunoassays (RIA). Chromatographic characterization showed that the NPY mainly consisted of intact NPY (1-36) and sulphoxidated form of NPY, no short C-terminal homologues were found. This is of importance since it has been shown that NPY (1-36) has different biological properties compared to C-terminal homologues.

Animals↗
PubMed1995

Limbic effects of repeated electroconvulsive stimulation on neuropeptide Y and somatostatin mRNA expression in the rat brain.

The aim of this study was to determine the effect of repeated electroconvulsive stimulation (ECS) on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA in the rat brain. For that purpose, quantitative in situ hybridization histochemistry and RNA blot analysis were used. In the hippocampal formation the prevalence of NPY mRNA positive neurons increased in the hilus of the dentate gyrus and the CA3 while a decrease was seen in layers II-III of the entorhinal cortex. In contrast, SS mRNA was increased in the granule cells of the dentate gyrus and in most neurons of the outer parts of the layer III in the entorhinal cortex with cell bodies of perforant pathway projections to the hippocampal CA1 region. Both NPY and SS mRNA expressing neurons were increased in numerical density in the prefrontal cortex with similar amounts of mRNA in individual NPY positive neurons after the stimulations while SS mRNA levels decreased in hybridization positive neurons. In the striatum the only observed significant effect was an increased prevalence of NPY mRNA positive neurons in the caudal nucleus accumbens. Our results provide an outline of a complex functional anatomy of ECS in the rat brain. This type of investigations contributes to map the neuronal systems involved in the action of ECT used in the treatment of affective and schizophrenic disorders.

Animals↗
PubMed1995

Chronic dietary lithium inhibits basal c-fos mRNA expression in rat brain.

1. Lithium is the most effective prophylactic agent used in the treatment of bipolar disorder. Although the acute effects of lithium include an inhibitory action on the phosphatidylinositol (PI) system, the longer term effects on signal transduction processes linked to this system are poorly understood. 2. An important consequence of activation of receptors linked to the PI pathway is activation of protein kinase C (PKC), which is involved in the induction of the proto-oncogene, c-fos. 3. The authors hypothesized that chronic lithium treatment, by inhibiting signaling through the PI/PKC pathway, might alter the expression of fos. 4. It was found that basal expression of c-fos was significantly reduced in cortical, hippocampal and hypothalamic brain areas of rats fed dietary lithium for 4 weeks. 5. The present results suggest that some of the effects of chronic lithium treatment may be mediated by alterations in signal transduction mechanisms linked to fos expression.

Animals↗