Biomedical subjects

E M Pich

Publications and source records attributed to E M Pich.

At least 37 records · Page 2Linked to original sources

PubMed1994

IL-1 beta potentiates the acetylcholine-induced release of vasopressin from the hypothalamus in vitro, but not from the amygdala.

In addition to the magnocellular hypothalamic nuclei, arginine vasopressin (AVP)-containing neurons have also been identified in limbic structures, including the hippocampus and amygdala. In the present study, we compared the qualitative properties of the in vitro release of AVP from the dissected hypothalamus with the in vitro release from the dissected amygdala and used these release systems to evaluate the interactions with neurotransmitters and cytokines. The areas of the paraventricular nucleus and supraoptic nucleus that contain the AVP neurons and that receive cholinergic innervation are also interleukin (IL)-1 beta immunoreactive. Acetylcholine or high KCl (60 mM) induces AVP release in both regions, and the AVP release is calcium dependent. Acetylcholine-induced AVP release is antagonized by atropine or mecamylamine, indicating that both muscarinic and nicotinic receptors are mediating the cholinergic effect in these brain regions. IL-1 beta (100 U/ml) had no effect on the basal AVP release from the hypothalamus, but significantly potentiated the acetylcholine-induced AVP release, lowering the threshold from 500 to 100 nM. This effect was completely blocked in the presence of neutralizing antibodies to IL-1 beta, atropine (10 microM) or mecamylamine (10 microM). IL-6, like IL-1 beta, also potentiated acetylcholine-induced AVP release, but to a lesser extent. Neither tumor necrosis factor-alpha nor interferon-gamma had any effect on the basal or acetylcholine-induced AVP release from the hypothalamus. None of the cytokines tested had any effect on the basal or acetylcholine-induced AVP release from the amygdala. Our results suggest a hypothalamic site of action of IL-1 beta and IL-6 on the acetylcholine-induced AVP release. The stimulatory effects of IL-1 and IL-6 on adrenocorticotropin release have been ascribed to an increased release of corticotropin-releasing factor (CRF). These data further suggest that, in addition to CRF, AVP plays a role in the bidirectional communication between neuroendoc ine and immune systems. Understanding the mode of interaction between IL-1 beta and IL-6 with AVP could clarify pathophysiologic or toxic effects of high brain levels of these cytokines.

Acetylcholine↗

PubMed1993

The role of limbic and hypothalamic corticotropin-releasing factor in behavioral responses to stress.

CRF in the central nervous system appears to have activating properties on behavior and to coordinate behavioral responses to stress. These behavioral effects of CRF appear to be independent of the pituitary-adrenal axis and can be reversed by a CRF antagonist, alpha-helical CRF9-41. The CRF antagonist reverses not only decreases in behavior associated with stress, but also increases in behavior associated with stress, thus suggesting that the role of CRF is stress dependent and not intrinsic to a given behavioral response. Further, microinjection of alpha-helical CRF9-41 and immunotargeting of CRF neurons in separate brain compartments reveal a link between the anatomical sites that contain CRF and the nature of the behavioral response to stress that can be modified by suppression of endogenous CRF activity therein. Hence, consistent with the dual role of other hypothalamic-releasing factors in integrating hormonal and neural mechanisms by acting both as secretagogues for anterior pituitary hormones and as extrapituitary peptide neurotransmitters, CRF may coordinate coping responses to stress at several bodily levels (Fig. 6). Moreover, dysfunction in such a fundamental homeostatic system may be the key to a variety of pathophysiological conditions including mental disorders.

Animals↗

PubMed1993

Functional impairment of hypothalamic corticotropin-releasing factor neurons with immunotargeted toxins enhances food intake induced by neuropeptide Y.

Previous work has shown that administration of corticotropin-releasing factor (CRF) into the lateral ventricle antagonizes the orexigenic effect of neuropeptide Y (NPY), and central injection of CRF antagonist, alpha-helical CRF(9-41) enhanced NPY-induced food intake in satiated rats. The aim of the present study was to determine the effects of selective inactivation of hypothalamic CRF neurons on food intake induced by NPY injection and to delineate which hypothalamic nucleus is involved in this NPY/CRF interaction related to the regulation of food intake. Impairment of CRF neuron function by immunotargeting of a ricin A chain toxin with a monoclonal antibody to CRF (CRF-MAb) has been previously reported. Administration of CRF-MAb/toxins into the paraventricular nucleus (PVN) two weeks prior to testing produced markedly enhanced eating induced by injection of NPY into the same nucleus. This effect was accompanied by a 60% decrease in CRF content within the hypothalamus and a 43% decrease of CRF in the median eminence, a site of projection of CRF neurons from the PVN. In contrast, injection of CRF-MAb/toxins into the ventromedial nucleus of the hypothalamus (VMH) did not modify the feeding induced by NPY injection into this hypothalamic area. Systemic pretreatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the levels of CRF in the PVN also enhanced the feeding induced by intra-PVN injection of NPY. This suggests that an equilibrium between CRF and NPY neuronal function within the PVN may play an important role in the regulation of food intake. This interactive mechanism may provide some partial explanation of the eating disorders related to stress, in particular anorexia nervosa.

Animals↗

PubMed1993

Indole-pyruvic acid, a tryptophan ketoanalogue, antagonizes the endocrine but not the behavioral effects of repeated stress in a model of depression.

Increased glucocorticoid secretion is frequent in mood disorders and is normalized by long-term antidepressant therapy. Many antidepressants act by increasing central serotonin transmission. We investigated the effects of a serotonin precursor, indole-pyruvic acid (IPA), in an animal model of depression based on repeated exposure to unpredictable stress. Rats were divided in groups, and IPA (20 mg/kg), the tricyclic antidepressant imipramine (IMI) (5 mg/kg), or vehicle was administered daily during 3 weeks of repeated exposure to various stressors according to the procedure described by Katz et al [Katz RJ, Roth KA, Carroll BJ (1981): Neurosci Biobehav Rev 5:247-251]. After treatment, rats were evaluated for stress-induced exploratory behavior and killed 24 hr later. Serum corticosterone levels and glucocorticoid receptor (GR) immunoreactivity (IR) in the nuclei of neurons located in the hippocampal subregion CA1 were also measured. Rats exposed to repeated stress showed a lower exploratory behavior score (p < 0.01), higher basal corticosterone levels (p < 0.01), and stronger GR IR in the hippocampus (p < 0.05) than control rats. All of these effects were antagonized by IMI treatment. IPA administration did not affect the behavioral response induced by repeated stress (p < 0.01) but normalized serum corticosterone levels. In addition, IPA treatment produced a decrease in GR IR (p < 0.05 versus control group) that was not modified by exposure to repeated stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1993

Corticotropin-releasing factor in the paraventricular nucleus modulates feeding induced by neuropeptide Y.

Central administration of neuropeptide Y (NPY) exerts a potent orexigenic effect in rats, whereas injection of corticotropin-releasing factor (CRF) suppresses food intake. Anatomical evidence of NPY-containing terminals located in close proximity to CRF-containing neurons and terminals of the hypothalamus and amygdala suggests possible interactions of these neuropeptide systems in food-intake regulation. The present study examined the effect of local administration of the CRF antagonist, alpha-helical CRF9-41, or peripheral treatment with dexamethasone on NPY-induced hyperphagia. Injection of a 250-ng dose of alpha-hel CRF within the paraventricular nucleus (PVN) of the hypothalamus significantly potentiated the feeding induced by a 500-ng dose of NPY injected into the same locus. In contrast, feeding induced by administration of the 500-ng dose of NPY into the ventromedial hypothalamus (VMH) was not modified by intra-VMH pre-treatment with a 250-ng dose of CRF antagonist. No effects of NPY or alpha-hel CRF on feeding were observed after administration into the central nucleus of the amygdala. Systemic pre-treatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the function of CRF neurons in the PVN (100 micrograms/kg) enhanced feeding induced by intra-PVN administration of a 500-ng dose of NPY. These results suggest that hypothalamic CRF systems in the PVN exert inhibitory control over NPY-induced food intake.

Animals↗

PubMed1993

Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides.

The function of neuropeptide Y, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists. An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the rat Y1 receptor was constructed and added to cultures of rat cortical neurons. This treatment resulted in a reduced density of Y1 (but not Y2) receptors and diminished the decrease in adenosine 3',5'-monophosphate (cAMP) usually seen after Y1 receptor activation. Repeated injection of the same oligodeoxynucleotide into the lateral cerebral ventricle of rats was followed by a similar reduction of cortical Y1 (but not Y2) receptors. Such antisense-treated animals displayed behavioral signs of anxiety. Thus, specific inhibition of neurotransmitter receptor expression can be accomplished in the living brain and demonstrates that altered central neuropeptide Y transmission produces an anxiety-like state.

Animals↗

PubMed1993

Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats.

The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension.

Animals↗

PubMed1993

The role of corticotropin-releasing factor in behavioural responses to stress.

Corticotropin-releasing factor (CRF), when administered directly into the CNS, can have activating properties on behaviour and can enhance behavioural responses to stress. CRF injected intraventricularly produces a dose-dependent increase in locomotor activity and increased responsiveness to an acoustic startle stimulus. However, this profile of activation changes to enhanced suppression of behaviour in stressful situations and includes increased freezing, increased conditioned suppression, increased conflict, decreased feeding and decreased behaviour in a novel open field. These effects of CRF are independent of the pituitary-adrenal axis and can be reversed by the CRF antagonist alpha-helical CRF(9-41). More importantly, the CRF antagonist can also reverse many behavioural responses to stressors. alpha-Helical CRF(9-41) reverses stress-induced fighting behaviour, stress-induced freezing, stress-induced suppression of feeding, stress-induced decreases in exploration of an elevated plus maze, fear-potentiated startle and the development of conditioned suppression. Intracerebral microinjections suggest that the amygdala may be an important site for the anti-stress effects of alpha-helical CRF(9-41). These results suggest that endogenous CRF systems in the CNS may have a role in mediating behavioural responses to stress and further suggest that CRF in the brain may function as a fundamental behavioural activating system. This CRF system may be particularly important in situations where an organism must mobilize not only the pituitary-adrenal system but also the CNS in response to environmental challenge.

Animals↗

PubMed1993

Involvement of alpha 2-receptors in the analgesia induced by transient forebrain ischemia in rats.

Transient forebrain ischemia induced in rats by the four-vessel occlusion method produced analgesic effects in the hotplate test that persisted for 2 weeks. Ischemia-induced analgesia was attenuated by low doses of alpha 2-agonist clonidine (0.01-0.10 mg/kg, IP) and enhanced by low doses of alpha 2-antagonists yohimbine (1-2 mg/kg, IP) and idazoxan (0.25-1.00 mg/kg, IP) administration 7 days after ischemia. Ischemia-induced analgesia was not affected by methysergide, naloxone, propranolol, or phenoxybenzamine administered 7 days after ischemia, when motor control and arousal level of rats recovered to normal conditions. The enhanced response to yohimbine was antagonized by pretreatment with clonidine (0.75 mg/kg, IP) and naloxone (10 mg/kg, IP), suggesting the involvement of endogenous opioid peptides. The enhanced response to yohimbine was still present 2 months after ischemia, when preischemic hotplate threshold was restored. As alpha 2-agonists reduce and alpha 2-antagonists increase the outflow of central noradrenaline, it is suggested that activation of central noradrenergic systems is involved in the mediation of ischemia-induced analgesia.

Adrenergic alpha-Antagonists↗

PubMed1993

Corticotropin-releasing factor release from the mediobasal hypothalamus of the rat as measured by microdialysis.

Procedures were developed to permit the measurement of corticotropin-releasing factor in perfusate collected from microdialysis probes implanted in various brain areas of anesthetized and awake rats. Initially in vitro experiments were carried out to optimize the recovery of corticotropin-releasing factor and the radioimmunoassay conditions. Addition of a specific antiserum against corticotropin-releasing factor to the perfusion medium (artificial cerebrospinal fluid) increased the relative in vitro recovery over a range of different flow rates (1-10 microliters/min) using commercially available microdialysis probes with a membrane cutoff of 20,000 mol. wt. This procedure increased recovery from 3% to 6% at flow rate of 2.5 microliters/min, and from 4% to 8% at a flow rate of 5 microliters/min. In vivo experiments were performed with a flow rate of 3.3 microliters/min and 50-microliters fractions were used for radioimmunoassay. In each experiment, the standard curve of the radioimmunoassay was constructed from aliquots of the same medium used to perfuse the probe. Basal levels of corticotropin-releasing factor in dialysate collected from the mediobasal hypothalamus of anesthetized rats were estimated to be 0.75 +/- 0.07 fmol/50 microliters. Raising the concentration of potassium (60 mM) in the perfusate increased corticotropin-releasing factor levels to 2.04 +/- 0.37 fmol/50 microliters. Hypertonic stress induced by intraperitoneal injection of 1.5M NaCl (20 ml/kg) elevated the levels to 1.32 +/- 0.07 fmol/50 microliters. A marked increase of corticotropin-releasing factor levels was also produced by a 10-min pulse of the potassium-channel blocker 4-aminopyridine (10 mM) included in the perfusate. A second stimulation pulse with 4-aminopyridine, administered 2 h after the first pulse again increased the levels, with a mean ratio between the first and second pulse of 0.97. Corticotropin-releasing factor efflux produced by the second stimulation pulse was completely inhibited by perfusion with calcium-free medium containing calcium-chelating agent ethyleneglycol tetraacetic acid (10 mM). In separate experiments, microdialysis probes were implanted in several brain areas of anesthetized rats. Basal and potassium-evoked levels of corticotropin-releasing factor were measured in dialysate collected from the amygdala (1.20 +/- 0.22 and 2.05 +/- 0.48 fmol/50 microliters, respectively) and frontal cortex (0.51 +/- 0.10 and 1.64 +/- 0.15 fmol/50 microliters, respectively). Corticotropin-releasing factor levels in the dorsal part of the third ventricle and in the striatum were below the detection limits. In awake rats, corticotropin-releasing factor levels in the mediobasal hypothalamus were 0.98 +/- 0.03 fmol/50 microliters.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1993

Blockade of pituitary-adrenal axis activation induced by peripheral immunoneutralization of corticotropin-releasing factor does not affect the behavioral response to social defeat stress in rats.

Specific in vivo immunoneutralization of hypophysiotrophic corticotropin-releasing factor (CRF) and vasopressin (AVP) was used to investigate the respective roles of these circulating peptides in the hormonal response to a social stressor in Wistar rats. The effect of peripheral immunoneutralization on the behavioral response to the same social stressor was also studied. Stress was produced using social defeat in a resident-intruder paradigm, in which an intruder male rat, equipped with an indwelling IV catheter, was confronted with a dominant resident male rat. To minimize the physical component of the agonistic interaction, the intruder was protected immediately after the resident's first attack in a Plexiglas/wire-mesh enclosure. In the following time interval, the resident continued to threaten the protected intruder, which showed a significant increase in plasma immunoreactive adrenocorticotropic hormone (ACTH) and corticosterone levels compared to those measured in rats exposed to a control procedure. The hypothalamo-pituitary-adrenal (HPA) axis response to social defeat stress was totally abolished by pretreatment with an anti-CRF serum (0.3 ml IV) but not an anti-AVP serum (0.75 ml IV). An animal model for anxiety in rodents, the elevated plus-maze, was used to study the emotional response to social defeat stress in rats given anti-CRF serum or normal serum. A significant reduction of open-arm exploration was observed in defeated rats tested 10 min after the end of the agonistic interaction when compared with control animals for all antisera treatment group, indicating an "anxiogenic-like" emotional response to the social defeat stress. Pretreatment with anti-CRF serum did not affect the behavioral performance of defeated and control rats. These results suggest that: 1) social defeat stress produced an activation of the HPA axis in the rat which is mediated by hypophysiotrophic CRF but not AVP; and 2) the peripheral activation of the HPA axis induced by social defeat stress is not involved in the behavioral response to stress as measured in the elevated plus-maze.

Adrenocorticotropic Hormone↗

PubMed1993

Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure.

We evaluated plasma atrial natriuretic factor (ANF), beta-endorphin, met-enkephalin, dynorphin and noradrenaline levels in 20 healthy subjects and 20 acute congestive heart failure (CHF) patients. In all acute CHF patients plasma values of these hormones were higher than in healthy subjects. The hormonal pattern differed in patients with the more severe acute CHF (group 1) from patients with less severe acute CHF (group 2) (ANF 53.8 +/- 1.0 vs 34.6 +/- 1.5 pg.ml-1, noradrenaline 563.8 +/- 13.4 vs 202.4 +/- 10.6 pg.ml-1, met-enkephalin 41.0 +/- 3.2 vs 17.0 +/- 1.6 fmol.ml-1, dynorphin 46.8 +/- 3.7 vs 25.2 +/- 2.0 fmol.ml-1, P < 0.01; beta-endorphin 50.6 +/- 5.2 vs 41.8 +/- 4.1 fmol.ml-1,ns). Administration of an opioid antagonist (naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentration in healthy subjects. In group 1 naloxone administration significantly raised ANF (68.0 +/- 1.4 pg.ml-1), noradrenaline (776.6 +/- 18.7 pg.ml-1), blood pressure and heart rate, whereas in group 2 it significantly decreased ANF values (21.9 +/- 0.5 pg.ml-1) and did not modify the other parameters. Our findings suggest that the opioid system affects ANF release in acute CHF. In patients with severe CHF opioid peptides may attenuate ANF secretion reducing noradrenergic stimulation. On the other hand, when CHF is less severe and the sympathetic activity is moderate, opioid peptides may directly stimulate ANF secretion.

Acute Disease↗

PubMed1992

Corticotropin-releasing factor antagonist reduces emotionality in socially defeated rats via direct neurotropic action.

Introduction of a socially naive male rat into the home territory of a resident counterpart results in agonistic interactions, leading to the rapid social defeat of the intruder. Exposure to the aggressive resident produces a stress-response profile consisting of neuroendocrine activation and coping behaviors such as submission. The present studies examined the dependence of these adaptive responses on endogenous brain Corticotropin-Releasing Factor (CRF), a peptide hormone known to coordinate neuronally mediated- and pituitary-adrenal responses to stress. The Elevated Plus-Maze was employed as an animal model of emotionality in which stressors reduce subsequent exploration of open maze arms without walls in favor of enclosed maze arms. A CRF antagonist, alpha-hel CRF9-41, administered intracerebroventricularly (5 and 25 micrograms i.c.v.) immediately post-stress and 5 min prior to maze testing reversed the heightened emotionality produced by the resident exposure stressor. This action paralleled that of an anxiolytic dose of the short-acting benzodiazepine, midazolam (1.5 mg/kg i.p.). Intra-amygdaloid administration of lower doses of the CRF antagonist (125, 250 and 500 ng i.c.) also reversed, dose-dependently, the effect of exposure to an aggressive resident without altering the behavior of unstressed control animals. Further, the enhanced release of ACTH and corticosterone following social conflict was not modified over the short term by the intra-amygdaloid dose of CRF antagonist (250 ng i.c.) which was effective in reversing stress-induced hyper-emotionality. These results suggest that limbic system CRF substrates exert an anxiogenic effect on the exploratory behavior of socially defeated rats via a pituitary-adrenal-independent mechanism.

Adrenocorticotropic Hormone↗

PubMed1992

Feeding and drinking responses to neuropeptide Y injections in the paraventricular hypothalamic nucleus of aged rats.

Neuropeptide Y (NPY), a peptide of the pancreatic polypeptide family, exerts a potent stimulatory action on eating when injected into the paraventricular hypothalamic nucleus (PVN) in rats. Several NPY-containing systems are altered with advancing age, and aged rodents develop anorexia and a modified daily cycle pattern of feeding. These findings suggest that a relationship may exist between the aging-related anorexia and the reduced function of NPY-containing systems projecting to the PVN. In the present study eating and drinking behavior in satiated or fasted young (3 months) and aged (24 months) rats have been investigated over 22 h after NPY injection into the PVN. The levels of NPY immunoreactivity (IR) in PVN were also evaluated by means of semiquantitative immunocytochemistry. NPY injections into PVN increased food and water consumption in both young and aged satiated rats 30, 90 and 240 min after injection. However, the feeding and drinking responses elicited by 0.05, 0.10 and 1.0 nmol of NPY were significantly attenuated in the aged rats when compared to young rats. In aged rats, 24 h of food and water deprivation produced significant increase of food consumption measured at 30, 90 min and 22 h, which was equivalent to that induced by 1.0 nmol NPY injection. Administration of 1.0 nmol NPY in PVN did not further increase the 24 h deprivation effect on feeding in both groups of rats, but enhanced drinking in deprived young rats. This effect was not present in aged rats. In addition, aged rats showed a stronger response to 24 h deprivation than to 1.0 nmol NPY administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1992

Plasma endogenous opioid levels in acute myocardial infarction patients, with and without pain.

Plasma levels of beta-endorphin, met-enkephalin and dynorphin were assessed in acute myocardial infarction (AMI) patients, with and without pain (group I: no pain, N = 12; group II: severe pain, N = 16). Plasma opioid peptide concentration was measured on admission to hospital (between 1 and 3 h after the myocardial infarction onset), at 7, 12, 24 h and at 2, 3 and 4 days. A transient increase in plasma beta-endorphin levels was found in AMI patients with severe pain, the levels normalizing within 12-18 h when pain had ceased. No changes in beta-endorphin concentration were observed in AMI patients without pain. Compared with healthy subjects, low levels of met-enkephalin were found in both groups of AMI patients throughout the study. Low levels of dynorphin were observed in patients with no pain while in the other patients initial low levels of dynorphin normalized when pain ceased. Blood pressure, heart rate and central venous pressure values were normal and did not correlate with plasma opioid levels. The results suggest that endogenous opioids do not affect pain in the early phase of myocardial infarction. The rise in beta-endorphin concentration observed in patients with severe pain seems to be induced by pain stress.

Aged↗

PubMed1991

Changes in striatal mu and delta opioid receptors after transient forebrain ischemia: a quantitative autoradiographic study.

Transient forebrain ischemia induces specific changes in several neurochemical markers in the dorsolateral striatum. In the present paper, the density and distribution of mu and delta opioid receptors were analyzed in rat striatum 7 days after 30 min forebrain ischemia using the 4-vessel occlusion model. A marked (about 70%) decrease in the density of both opioid receptor subtypes was found in the dorsolateral striatum overlapping the areas of histological damage and of D1 dopamine receptor disappearance. Moreover, the density of delta opioid receptors and of the diffuse mu opioid receptors was also affected (30% decrease) in the ventromedial striatum, an area which is substantially spared by the ischemic lesion. In contrast, the striatal patches of mu opioid receptors were not affected in the ventro-medial striatum and were preserved to a large extent in the area of lesion, although their area and receptor density resulted markedly reduced. The impairment of both opioid receptor subtypes suggests that opiate systems, like dopaminergic systems, are involved in the neurochemical changes observed in the striatum after transient forebrain ischemia.

Animals↗

PubMed1990

Evidence for a role of neosynthetized putrescine in the increase of glial fibrillary acidic protein immunoreactivity induced by a mechanical lesion in the rat brain.

The effect of alpha-difluoromethylornithine (alpha-DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) the rate limiting enzyme of polyamine biosynthesis, was studied on the astroglial reaction in a model of mechanical brain injury. alpha-DFMO markedly decreased the astroglial activation induced by the microdialysis probe implantation in the striatum of the male rat, as studied by glial fibrillary acidic protein (GFAP) immunocytochemistry. This response was restored by putrescine (20 nmol/ml) administered via the microdialysis probe. These results suggest that the astroglial reaction and the polyamine biosynthesis activation induced by a localized mechanical lesion are causally linked phenomena.

Animals↗

PubMed1990

Morphometrical and microdensitometrical studies on peptide- and tyrosine hydroxylase-like immunoreactivities in the forebrain of rats prenatally exposed to methylazoxymethanol acetate.

Methylazoxymethanol acetate (MAM Ac) injected into pregnant rats at a dose of 25 mg/kg at gestational day 15 causes microcephaly due to an atrophy of various telencephalic areas, mainly neocortex, hippocampus and basal ganglia. Previous studies demonstrated alterations in various neurochemical markers of classical transmitter systems in these regions. The present paper deals with changes in peptide and tyrosine hydroxylase (TH)-containing neurons in MAM Ac-induced microcephaly using immunocytochemistry coupled with computer-assisted morphometry and microdensitometry. No change in the number of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in the neocortex and neuropeptide Y (NPY)-immunoreactive neurons in the nucleus caudatus-putamen was found whereas cholecystokinin (CCK)-and NPY-immunoreactive neurons in the neocortex and CCK- and VIP-immunoreactive neurons in the hippocampus were decreased. The reduction of the latter peptide containing neuronal populations led to a maintained density of cells in MAM Ac-exposed rats, due to the parallel reduction of the overall mass of these regions. TH immunoreactivity was found to be unchanged in the basal ganglia, and increased in the cerebral cortex in agreement with previous reports on noradrenaline cortical system after MAM Ac exposure. The present results show a heterogenous vulnerability of different peptide immunoreactive neuronal populations to MAM Ac exposure. The sparing of VIP- and NPY-immunoreactive neurons may be due to their late development in the neocortex and striatum, respectively. The hypothesis is introduced that cortical VIP interneurons can develop independent of marked alterations in the intrinsic circuitry of the cortical region.

Animals↗