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M Iadarola

Publications and source records attributed to M Iadarola.

16 recordsLinked to original sources
PubMed2004

CNS activation by noxious heat to the hand or foot: site-dependent delay in sensory but not emotion circuitry.

Recently, functional magnetic resonance imaging has been used as a novel method of evaluating the CNS response to noxious stimuli. In a previous study, a prolonged noxious thermal stimulus applied to the dorsum of the hand produced more than one hemodynamic response that was temporally segregated. The two major responses displayed activation in primary sensory regions (classic pain circuitry) and regions involved in emotion (reward/aversion circuitry), respectively. In the current study, we applied the same thermal stimulus separately to the dorsum of the left foot and the dorsum of the left hand in the same subjects and compared the hemodynamic responses to evaluate the effects of conduction distance on CNS activation within these two segregated systems. After stimulus delivery to the foot, the hemodynamic response in primary sensory networks occurs after a delay of 3.6 +/- 1.3 s as compared with the response after hand stimulation. The relative delay of the hemodynamic response in reward/aversion regions is not significantly different between hand and foot stimulation (0.6 +/- 2.1 s). These results within the primary sensory system are consistent with the greater conduction distance of the peripheral nerves from the hand versus the foot. The observation that the response within the reward/aversion pathways occurs with the same rapid temporal characteristics after either hand or foot stimulation supports the notion that the circuitry involved in the evaluation of aversive stimuli is rapid in onset and probably represents a major protective mechanism for survival.

Adult↗
PubMed2002

Local circuit neurons in the striatum regulate neural and behavioral responses to dopaminergic stimulation.

Interneurons are critical for shaping neuronal circuit activity in many parts of the central nervous system. To study interneuron function in the basal ganglia, we tested and characterized an NK-1 receptor-based method for targeted ablation of specific classes of interneuron in the striatum. Our findings demonstrate that the neurotoxin SP-PE35, a substance P-Pseudomonas exotoxin conjugate, selectively targets striatal cholinergic and nitric oxide synthase/somatostatinergic interneurons when injected locally into the striatum. The effects of this selective cell targeting encompassed alterations in both behavioral and neural responses to dopaminergic stimulation, including altered patterns of early-gene response in striosomes and matrix. We conclude that NK-1-bearing local circuit neurons of the striatum regulate the differential responses of striatal projection neurons to dopamine-mediated signaling.

Animals↗
PubMed2000

Cloning and expression of MP13 gene from rat hippocampus, a new factor related to guanosine triphosphate regulation.

C-Fos and the Fos-related antigens (FRA) are induced by various stimuli. A novel 35-37 kDa FRA was induced much longer after the treatment using kainic acid (KA) and may be very important for neuronal survival after brain damage. To identify this long-term FRA, we have constructed a cDNA library derived from hippocampus after KA treatment and screened it with an antibody highly conserved M-peptide region of FRAs. One gene, MP13, was cloned with a 1662 bp open reading frame and coded for a 554-amino acid protein. MP13 has a leucine zipper region, a glutamine repeat region, and has high similarity to the activator of the small guanosine triphosphate (GTP)ase Rab5. Gel retardation analysis revealed that MP13 functions as a GTP regulation related factor.

Amino Acid Sequence↗
PubMed1996

Long-term expression of the 35,000 mol. wt fos-related antigen in rat brain after kainic acid treatment.

Systemic injection of kainic acid, a rigid analogue of glutamate, induces both the short-term and the long-term expression of activator protein-1 transcription factors. The short-term responses of activator protein-1 factors such as c-fos and fos-related antigens have been well studied. However, the long-term expression of activator protein-1 factor(s) induced by kainic acid is poorly understood. The present study was designed to document the long-term expression (up to seven months) of the fos-related antigens and to map their distributions in the rat brain after systemic treatment with kainic acid. A single dose of kainic acid (8 mg/kg) was injected i.p. into Fischer 344 rats and their epileptic seizure behaviour was monitored. The rats with full limbic seizures were chosen for long-term study. By using immunocytochemistry with an antibody that cross-reacts with all known fos-related antigens, western blot analysis and a gel mobility-shift assay, we have now shown that a 35,000 mol. wt fos-related antigen was induced by kainic acid treatment and expressed at high levels for up to five months. This fos-related antigen still maintains the activator protein-1 DNA binding activity in the rat brain seven months after kainic acid treatment. The fos-related antigens and activator protein-1 binding activity were continuously expressed at high levels throughout the experimental period in the dentate granule cells where mossy fibre collateral sprouting occurred after kainic acid treatment. Our results suggested that long-term expression of fos-related antigen may reflect the pathophysiological changes after kainic acid administration.

Animals↗
PubMed1996

Expression of Fos-related antigens, oxytocin, dynorphin and galanin in the paraventricular and supraoptic nuclei of lactating rats.

The magnocellular oxytocin neurons within the paraventricular and supraoptic nuclei (PVN and SON) of the hypothalamus are important relays in the milk ejection reflex in lactating animals, and are activated by suckling. It has been suggested that proto-oncogene transcription factors such as Fos/Jun act as early nuclear transducers of sensory stimuli in neurons. Therefore, we have studied with immunohistochemistry Fos-related antigens (FRAs) as a marker for neuronal activity in the PVN and SON during suckling in lactating rats. In nonlactating rats, only few cells exhibiting FRAs were observed in these nuclei. Also in lactating rats subjected to continuous suckling Fos-like activity was low. In contrast, lactating rats separated from their pups for 4 h and then exposed to suckling for 1 h expressed strong Fos-like immunoreactivity, both in vasopressin and oxytocin neurons. Using in situ hybridization and immunohistochemistry we have also investigated the expression of the mRNAs for oxytocin, dynorphin, galanin and galanin message-associated peptide and of oxytocin and dynorphin in the PVN of lactating and nonlactating rats. In lactating rats, an increase in oxytocin and dynorphin and their mRNAs was observed, whereas mRNAs for galanin and galanin message-associated peptide were downregulated. With the help of immunohistochemistry and double-staining methods, a substantial coexistence between oxytocin- and dynorphin-like immunoreactivities was shown in magnocellular neurons. These results indicate that FRAs are activated in the PVN in the beginning of a suckling period, while this response cannot be seen after continuous stimulation. Furthermore, in the PVN of lactating rats, an upregulation of oxytocin and dynorphin occurs while galanin expression decreases. Finally, the coexistence between oxytocin and dynorphin is more pronounced in lactating rats and nonlactating female rats than has previously been described in male rats.

Animals↗
PubMed1995

Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens.

Previous work has demonstrated that chronic administration of cocaine induces apparently novel Fos-like transcription factors, termed chronic Fras (Fos-related antigens), in the rat striatum and nucleus accumbens. Induction of these proteins is associated with prolonged increases in AP-1 DNA binding activity that parallel the long half-life of the chronic Fras in brain. The goal of the present study was to characterize pharmacologically the regulation of chronic Fra induction by cocaine. Chronic Fra induction was examined with respect to the cocaine dose, time course and administration intervals used. Cocaine was found to induce the chronic Fras over widely differing treatment regimens in the striatum and nucleus accumbens, although clear differences between the two brain regions were observed. In general, maximal induction occurred with moderate treatment conditions, with more or less intensive treatments resulting in lower levels of chronic Fras. The pharmacological mechanisms underlying cocaine induction of the chronic Fras were also investigated. Pretreatment with a D1 receptor antagonist, which did not affect chronic Fra levels by itself, attenuated cocaine induction of the chronic Fras in striatum and nucleus accumbens. In contrast, treatment with a D2 receptor antagonist alone greatly induced chronic Fra levels, with no further increase seen in response to combined treatment with cocaine. Combined treatment with D1 and D2 receptor agonists, or with amphetamine, led to a strong induction of chronic Fras. Similarly, repeated treatment with a specific dopamine transporter inhibitor increased chronic Fra levels, whereas treatment with a specific serotonin or norepinephrine transporter inhibitor failed to produce this effect. These results support an important role for dopaminergic neurotransmission in the induction of chronic Fras by cocaine. Taken together, the results of the present study provide a more complete understanding of the pharmacological properties underlying cocaine regulation of the chronic Fras, which will assist in identifying the functional role played by these proteins in cocaine action.

Animals↗
PubMed1992

Fos-like immunoreactivity in the rat hypothalamic-pituitary axis after immobilization stress.

The effect of immobilization stress on the expression of the protooncogene c-fos in the rat pituitary and hypothalamus was investigated immunohistochemically using different polyclonal antibodies raised against the c-fos protein (Fos). After a 4 h immobilization, Fos-like immunoreactivity (Fos-LI) increased substantially in the parvocellular part of the paraventricular nucleus and in the intermediate and anterior lobe of the pituitary. The majority of the Fos-immunoreactive cells in the pituitary contained corticotropin, which was demonstrated by immunohistochemical double-staining. Since the paraventricular nucleus contains a large number of glucocorticoid receptor immunoreactive cells, the effect of a synthetic glucocorticoid, dexamethasone, on the induction of Fos-LI was studied. Dexamethasone treatment before immobilization considerably reduced the stress-induced expression of Fos-LI in the anterior and intermediate lobe of the pituitary but did not alter the induction of Fos-LI in the paraventricular nucleus. The present results demonstrate that immobilization stress induces Fos-LI both in the hypothalamus and in the pituitary, suggesting that Fos may be involved in regulating the synthesis of different mediators of stress response, such as CRF- and POMC-derived peptides. Apparently glucocorticoids do not directly repress c-fos expression, since dexamethasone did not affect the induction of Fos-LI in the paraventricular nucleus. The reduction of stress-induced Fos-LI in the pituitary by dexamethasone is possibly due to the diminished release of CRF factor from the paraventricular neurons.

Adrenocorticotropic Hormone↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Photic regulation of c-fos expression in neural components governing the entrainment of circadian rhythms.

The rapid and transient induction of the proto-oncogene c-fos in mature neurons within the brain occurs in response to a variety of extracellular stimuli. To determine whether lighting conditions influence c-fos gene expression in the primary neural structures mediating the photoentrainment and generation of mammalian circadian rhythms, the expression of the c-fos protein (Fos) and related proteins in the retina and suprachiasmatic nuclei (SCN) of the anterior hypothalamus was examined immunohistochemically in rats exposed to a light-dark cycle of 12 h of light and 12 h of darkness (LD 12:12), constant light (LL), or constant dark (DD). The retina exhibited clear light-dark differences in the expression of Fos protein(s), such that immunopositive nuclei were readily evident during exposure to light (i.e., during the day of diurnal lighting or in LL), but were absent during exposure to darkness. In the SCN, the distribution of Fos immunoreactivity within specific subfields was differentially affected by photic conditions. Following exposure to light, a dense population of Fos-immunopositive cells was found in close association with the immunohistochemically distinct cell and fiber populations distinguishing the ventrolateral subfield of the SCN. In dark-exposed animals, Fos-immuno-reactive profiles were distributed throughout the SCN in areas coextensive with the immunohistochemical localization of peptidergic neural elements in both the ventrolateral and dorsomedial subfields. As a consequence of this light-dark difference in the distribution of Fos immunoreactivity, the density of labeled cells was increased within the ventrolateral SCN, but was decreased within the dorsomedial subfield, as a result of exposure to light versus darkness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Distinct factors bind the AP-1 consensus sites in gibbon ape leukemia virus and simian virus 40 enhancers.

We have demonstrated that the gibbon ape leukemia virus (GALV) enhancer AP-1 element and the simian virus 40 AP-1 enhancer element bind different factors in HeLa nuclear extracts. A 39-kilodalton HeLa nuclear protein and the c-fos protein bind to the GALV element. Antibodies to c-fos abolish binding to the GALV AP-1 site. In contrast, anti-c-fos immunoglobulin fails to inhibit formation of the simian virus 40-specific complex from extracts of HeLa cells. Thus, AP-1-binding complexes are subject to compositional variation at different binding sites.

Animals↗
PubMed1988

Prefrontal cortical blood flow and cognitive function in Huntington's disease.

To examine the relationship between cortical physiology and dementia in Huntington's disease, rCBF during three different behavioural conditions, one of which emphasised prefrontal cognition, was determined by xenon-133 inhalation in 14 patients with Huntington's disease and in matched controls. Cortical rCBF was not reduced in Huntington's disease patients even while they manifested overt prefrontal-type cognitive deficits. Caudate atrophy on CT and rCBF were significantly correlated, but only during the prefrontal behaviour where the correlation was positive. These results suggest a qualification of the subcortical dementia concept as applied to Huntington's disease and implicate an interaction between pathology that is subcortical and cognitive function that is cortical.

Adult↗
PubMed1985

Neuropeptides in human brain--postmortem studies.

Four neuropeptides (substance P, methionine-enkephalin, neurotensin and cholecystokinin) were measured by radioimmunoassays in a number of brain regions of deceased patients with mental illnesses and controls. The most striking finding in these studies was that methionine-enkephalin concentrations in caudate nuclei of chronic paranoid schizophrenic patients were reduced relative to several control groups. Neuroleptics had no obvious effects on any of the four measured neuropeptides. These findings are not inconsistent with the hypothesis that methionine-enkephalin may be involved in some of the pathology of the schizophrenic syndrome.

Adult↗
PubMed1985

Are Phe-Met-Arg-Phe-NH2 immunoreactive peptides endacoids modulating opiate antinociception?

Phe-Met-Arg-Phe-NH2 (FMRF-NH2) was initially isolated from the macrocallista nimbosa clam and subsequently existence of FMRF-NH2-like immunoreactivity (FMRF-NH2-IR) was detected in mammalian CNS. Due to the structural similarity between FMRF-NH2 and the C-terminal extended form of met5-enkephalin, met5-enkephalin-arg6-phe7 (YGGFMRF), a possible interaction between these two peptides was explored. FMRF-NH2 injected intrathecally decreases the antinociceptive action of YGGFMRF or morphine. However, the FMRF-NH2-IR present in rat and bovine brains differs from FMRF-NH2. Intrathecally injected FMRF-NH2-IR partially purified from bovine brain reduces YGGFMRF antinociception. The antagonism elicited by FMRF-NH2 can be reversed by proglumide, which was reported to act as a CCK antagonist. In order to characterize the biological profile of FMRF-NH2-IR, the effect of proglumide and of the FMRF-NH2 antibody on morphine analgesia was tested. Both the IgG isolated from FMRF-NH2 antiserum and proglumide were found to potentiate the morphine analgesia. The results taken together suggest that endogenous FMRF-NH2-IR modulates opioid antinociception; perhaps by acting as an endogenous naloxone.

Animals↗
PubMed1984

Proglumide prevents and curtails acute tolerance to morphine in rats.

The antagonism of the antinociceptive action of morphine elicited by CCK-8-SO4 can be counteracted by proglumide, a CCK antagonist. The addition of morphine (10(-6)M) to the artificial spinal fluid perfusing the subarachnoidal space of rat spinal cord increases the CCK content of the perfusate. Proglumide can potentiate morphine analgesia without changing the half life of morphine. After seven to eight subcutaneous injections of morphine (4 mg/kg) repeated every two hrs there is tolerance to the antinociceptive action of morphine. Proglumide can partially block or reverse this acute tolerance to morphine.

Animals↗