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Biomedical subjects

I Ferrer

Publications and source records attributed to I Ferrer.

At least 199 records · Page 11Linked to original sources
PubMed1996

Abnormal, ubiquitinated cortical neurites in patients with diffuse Lewy body disease.

Although it is known that the severity of dementia in patients with diffuse Lewy body disease is related to cortical Lewy body density, the morphological substrate of dementia in these patients is poorly understood. Vibratome sections processed free-floating for ubiquitin immunohistochemistry in three patients with the common form and one patient with the pure form has shown the presence of large numbers of abnormal, ubiquitinated neurites in the cerebral cortex, mainly cingulate cortex, entorhinal cortex and temporal lobe, and hippocampal complex, regions in which, precisely, Lewy bodies are most abundant. Abnormal neurites are a consistent change which results in abnormal neuronal connectivity. Abnormal cortical neurites, rather than cortical Lewy bodies, may play a significant role in the development and progression of cognitive deficits in patients with diffuse Lewy body disease.

Adult↗
PubMed1996

CREB-1 and CREB-2 immunoreactivity in the rat brain.

This study is focused to learn about the cellular localization of transcription factors binding to the cAMP response element-CREBs-in the brain of normal rats and in animals subjected to excitotoxic cell damage. For this purpose, CREB-1 and CREB-2 immunoreactivity is examined in the developing and adult rat brain under physiological conditions, and following systemic kainic acid (KA) injection at convulsant doses in the adult, as a validated experimental model of excitotoxic injury. CREB-1 immunoreactivity is constitutively expressed in periventricular glia and Bergmann glia, and appears in reactive astrocytes following KA-induced excitotoxic cell damage. In contrast, CREB-2 is constitutively expressed in all neurons of the cerebrum, cerebellum and brain stem in the developing and adult brain. CREB-2 immunoreactivity is not increased following KA excitotoxic cell damage. These results demonstrate that CREB-1 and CREB-2 in the brain of the rat are localized in separate cellular compartments and that their expression is differentially regulated in pathologic states.

Animals↗
PubMed1996

Apoptosis and c-Jun in the thalamus of the rat following cortical infarction.

Cortical infarction produces secondary neuronal damage in the thalamus. In this study we examined the thalamus of the rat following 2 h occlusion of the middle cerebral artery (MCA), and found degeneration and gliosis in the ipsilateral ventropostero-medial thalamic nucleus in those rats that showed cortical infarction 7 and 14 days after occlusion. This was accompanied by isolated cells with fragmented DNA, as revealed by in situ labelling of nuclear DNA fragmentation, and showing morphological features of apoptosis, i.e. chromatin condensation, extreme nuclear shrinkage and apoptotic bodies. In addition, cells immunoreactive for c-Jun showing morphological signs of apoptosis were observed. These results provide evidence of apoptosis in the ipsilateral thalamus following cortical infarction, and suggest that c-Jun is involved in this process.

Animals↗
PubMed1996

Selective c-Jun overexpression is associated with ionizing radiation-induced apoptosis in the developing cerebellum of the rat.

Immunohistochemistry to Bcl-2, Bax, c-Myc, c-Fos, Fos-related, c-Jun, Jun B and Jun D was used to study the involvement of these factors in ionizing radiation-induced apoptosis in the cerebellum of the developing rat. Selective c-Jun overexpression was observed during the whole process of radiation-induced cell death. Furthermore, c-Jun overexpression was restricted to apoptotic cells, as shown by double labeling with the method of in situ labeling of nuclear DNA fragmentation and c-Jun immunohistochemistry. This is the first in vivo evidence that selective c-Jun overexpression is associated with apoptotic cell death in the developing nervous system following ionizing radiation.

Animals↗
PubMed1996

Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor-receptor (EGF-R) immunoreactivity in normal and pathologic brain.

Transforming growth factor alpha (TGF-alpha) and epidermal growth factor-receptor (EGF-R) immunoreactivity is observed in the majority of neurons, and in maturing astrocytes, in the developing and adult brain of humans and different species of animals. TGF-alpha and EGF-R co-localize in most neurons and maturing astrocytes, suggesting that most TGF-alpha-producing cells are EGF-R-expressing cells. TGF-alpha and EGF-R immunoreactivity decrease in damaged areas following different insults. However, EGF-R appears in reactive glia, mostly reactive astrocytes, within and surrounding the damaged areas. TGF-alpha and EGF-R immunoreactivity is found in neurons of patients affected by Alzheimer's disease and other forms of dementia, and in neurons of patients suffering from epilepsy owing to different causes, thus pointing to the conclusion that TGF-alpha does not play a significant role in these pathologies. However, EGF-R immunoreactivity occurs in reactive astrocytes and microglia in subacute but not chronic lesions in human cases. Since TGF-alpha is a membrane-anchored growth factor, which may be cleaved leading to the formation of soluble forms, and both the membrane-anchored and soluble forms have the capacity to activate the EGF-R, it is feasible that TGF-alpha in the nervous system may act upon EGF-R-containing neurons through different mechanisms. In addition to distant effects resulting from the release of soluble TGF-alpha, local effects may be produced by establishing direct cell-to-cell contacts (juxtacrine stimulation), or in cells expressing both TGF-alpha and EGF-R (autocrine stimulation).

Animals↗
PubMed1996

Cell death in the normal developing brain, and following ionizing radiation, methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat.

Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia-ischaemia in the developing rat brain. Ionizing radiation-induced cell death in the brain of the young rat has morphological characteristics of apoptosis, is mediated by protein synthesis and is associated with internucleosomal DNA fragmentation. Methyl-azoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c-Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to the molecular weight of c-Jun, in control rats. However, a thick c-Jun-immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM-treated rats. A thin band immediately above the thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c-Jun expression is associated with apoptotic cell death in the developing central nervous system.

Animals↗
PubMed1996

Amyloid deposition is associated with c-Jun expression in Alzheimer's disease and amyloid angiopathy.

Since the PAD gene (also called promoter of Alzheimer's disease amyloid A4 precursor gene or amyloid beta-protein precursor promoter) has two AP-1 consensus sequences, and members of the Fos and Jun families are the major components of the transcription factor activator protein-1 (AP-1), we have investigated the localization of c-Fos and c-Jun immunoreactivity and its relationship to beta-amyloid deposition in the brains of patients with Alzheimer's disease and amyloid angiopathy. c-Jun, but not c-Fos, immunoreactivity is observed in the muscular layer of meningeal and cerebral blood vessels with amyloid angiopathy, and in the soma of glial cells and cellular processes of unknown origin surrounding beta-amyloid deposits in the brain. These results show that c-Jun may participate in the cascade of events leading to increased beta-APP (beta-amyloid precursor protein) production and beta-amyloid deposition in the brains of patients with Alzheimer's disease and amyloid angiopathy.

Alzheimer Disease↗
PubMed1996

Naturally occurring (programmed) and radiation-induced apoptosis are associated with selective c-Jun expression in the developing rat brain.

Expression of the different members of transcription factors Fos and Jun was examined in the developing rat brain. Constitutive expression of c-Fos, Fos-related antigens, Jun B and Jun D, as revealed with immunohistochemistry, is higher and more widely distributed in the developing rat brain than in the adult. Selective strong c-Jun expression is observed in the cytoplasm and nuclei of apoptotic cells during the whole process of naturally occurring (programmed) cell death. Cells expressing strong c-Jun immunoreactivity are undetermined cells, neurons and astrocytes. Selective c-Jun expression is also observed following ionizing radiation in rats aged 3 days. Induction of c-jun mRNA, as revealed with in situ hybridization, occurs between 5 and 15 min following gamma-irradiation. Strong c-Jun protein expression appears at 2 h, peaks at 6 h and decreases thereafter to reach normal levels 48 h after gamma-ray exposure. Strong c-Jun protein expression is coincidental with endonuclease activation, as revealed with the method of in situ labelling of nuclear DNA fragmentation, and is restricted to apoptotic cells. Cycloheximide injection at the time of irradiation blocks c-Jun expression, indicating that c-Jun immunoreactivity is attributable to de novo protein synthesis. These observations demonstrate in vivo selective strong c-Jun expression associated with programmed cell death and ionizing radiation-induced apoptosis in the developing rat brain.

Animals↗
PubMed1996

Induction of Stat3, a signal transducer and transcription factor, in reactive microglia following transient focal cerebral ischaemia.

Stat3, a member of the family of cytoplasmic signal transducers and activators of transcription, was found in the rat brain in vivo under physiological conditions and was stimulated following transient focal cerebral ischaemia. A transient episode of middle cerebral artery occlusion induced a strong microglial response in the areas undergoing neural cell death from 4 days after middle cerebral artery occlusion. This was accompanied by increased expression of Stat3 in the ipsilateral cortex and striatum, as revealed by Western blotting of tissue extracts. Immunohistochemistry showed strong induction of Stat3 in reactive microglial cells 4, 7 and 15 days after cerebral ischaemia. Stat3 was seen in the microglia cytoplasm, but in many microglial cells immunoreactivity was also distributed within the nucleus. These results suggest that Stat3 mediates signal transduction and activates transcription in reactive microglia in vivo following brain ischaemia.

Animals↗
PubMed1996

Transient colocalization of parvalbumin and calbindin D28k in the postnatal cerebral cortex: evidence for a phenotypic shift in developing nonpyramidal neurons.

In the adult rat cerebral cortex the calcium-binding proteins parvalbumin and calbindin D28k are present in essentially non-overlapping populations of GABAergic interneurons. These proteins follow different developmental patterns in the cortex: calbindin D28k-immunoreactive nonpyramidal neurons are abundant until the second postnatal week and decrease markedly thereafter; it is at this time that parvalbumin immunoreactivity develops in cortical nonpyramidal neurons. To determine whether parvalbumin-immunoreactive neurons derive from calbindin D38k positive cells we used double-immunofluorescence studies for both calcium-binding proteins, together with combined immunocytochemistry for calbindin D28k and in situ hybridization for parvalbumin mRNA during postnatal development. Double-labelled cells were found in all cortical layers between P9 and P21, coinciding with the onset of parvalbumin expression. The percentage of colocalization of the two calcium-binding proteins depended on the age and layer examined. Colocalization reached a peak (80-100%) during the second postnatal week. Double-labelled neurons were rare in layer V at all ages studied. The present results indicate a phenotypic shift during the development of some cortical interneurons that halts the expression of calbindin D28k while parvalbumin expression starts. These findings agree with lineage analyses reporting that different types of nonpyramidal neuron arise from a common progenitor.

Animals↗
PubMed1996

Thalamic and basal forebrain afferents modulate the development of parvalbumin and calbindin D28k immunoreactivity in the barrel cortex of the rat.

In the adult barrel cortex of the rat the calcium-binding proteins calbindin D28k (CALB) and parvalbumin (PARV) are found in separate populations of GABAergic nonpyramidal neurons. In layers II to IV of the barrel cortex most PARV-immunoreactive neurons are likely to derive from a subpopulation of CALB-immunoreactive neurons whose CALB immunoreactivity ceases when they begin to express PARV between the second and third postnatal weeks. The aim of this study was to investigate the influence of subcortical afferents on the neurochemical differentiation of cortical PARV- and CALB-immunoreactive nonpyramidal neurons during development of the barrel cortex. We produced unilateral excitotoxic lesions with a single injection of ibotenic acid (0.5 microl, 0.05 M) in different subcortical nuclei in 7- to 8-day-old rats. Lesions involving the ventroposterior thalamic nuclei resulted in delayed development of PARV and CALB immunoreactivity in the barrel cortex. One week after ibotenic acid injections a transient decrease in the number of PARV-immunoreactive neurons in layer IV was observed, together with increased numbers of CALB-immunoreactive neurons in all cortical layers. The number of nonpyramidal neurons displaying coexistence of PARV and CALB in the lesioned hemisphere also increased compared with the numbers in the control hemisphere or control littermates. In contrast, lesions affecting the globus pallidus, zona incerta and reticular thalamic nucleus transiently increased the number of PARV-immunoreactive neurons in layers II and III, but had no effect on the number of CALB-positive cells. From 3 weeks onwards no differences were found between control and lesioned hemispheres after injections into either the ventroposterior thalamic nuclei or the magnocellular basal forebrain. These results suggest that CALB and PARV expression in nonpyramidal cortical neurons can be reversibly modulated in opposite directions by different cortical afferents during postnatal development.

Analysis of Variance↗
PubMed1996

The inhibitory effects of alpha(2)-adrenoceptor agonists on gastrointestinal transit during croton oil-induced intestinal inflammation.

1. The peripheral effects of alpha(2)-adrenoceptor agonists were investigated in a model of intestinal inflammation induced by intragastric administration of croton oil (CO). Our hypothesis was that inflammation would 'sensitize' adrenoceptors in peripheral and/or central terminals of myenteric and submucous plexus neurones, and enhance systemic effects of alpha(2)-adrenoceptor agonists. 2. Male swiss CD-1 mice, received intragastrically CO (0.05 ml), castor oil (CA, 0.1 ml) or saline (SS) 3 h before the study: gastrointestinal transit (GIT) was evaluated 20 min afterwards with a charcoal meal. The presence of inflammation was assessed by electron microscopy. 3. The intragastric administration of CA or CO caused an increase in GIT and weight loss, but only CO induced an inflammatory response. Both clonidine (imidazoline1/alpha(2)-agonist) and UK-14304 (alpha(2)-agonist) produced dose-related inhibitions of GIT in all groups. During inflammatory diarrhoea (CO), potencies of systemic (s.c.) clonidine and UK-14304 were significantly increased 3.5 and 2.1 times, respectively, while potencies remained unaltered in the presence of diarrhoea without inflammation (CA). The effects were reversed by administration (s.c.) of receptor-specific adrenoceptor antagonists, but not by naloxone. 4. Clonidine was 8.3 (SS) and 2.8 (CO) times more potent when administered intracerebroventricularly (i.c.v.), than when administered s.c. Inflammation of the gut did not alter the potency of i.c.v. clonidine, demonstrating that enhanced effects of s.c. clonidine are mediated by peripheral receptors. During inflammation, i.c.v. efaroxan did not antagonize low doses of s.c. clonidine (ED20 and ED50S), but partially reversed ED80S, further supporting the peripheral effects of the agonists in CO treated animals. 5. The results demonstrate that inflammation of the gut enhances the potency of alpha(2)-adrenoceptor agonists by a peripheral mechanism. The results also suggest that the inflammatory response induces an up-regulation or sensitization of alpha(2)-adrenoceptors and/or imidazoline receptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Malignant epithelioid schwannoma affecting the trigeminal nerve of a dog.

A malignant epithelioid schwannoma was diagnosed affecting the trigeminal nerve of an 11-year-old dog. Neurologic abnormalities included an altered mental status, ataxia, left head tilt, postural reaction deficits of all four limbs, a pronounced left masticatory muscle atrophy, and absent left facial sensation. Histologically, a densely arranged epithelioid population with a very high mitotic index was surrounded by a spindle-shaped cell proliferation characteristic of schwannomas. Both cell populations stained positively for vimentin, but only spindle cells were occassionally positive for S-100 protein. The histologic and immunohistochemical features of this tumor were consistent with those found in human epithelioid schwannomas.

Animals↗
PubMed1996

[Molecular factors of cerebral hypoxia-ischemia].

In recent years much has been learned about the cellular and molecular events underlying cerebral hypoxia-ischemia (HI). We review, from a molecular standpoint, the main pathogenetic theories in hypoxic-ischemic cerebral injury, including excitotoxicity, free radical damage, and the role of growth factors, proto-oncogenes and heat shock proteins. The various forms of cell death in the developing and adult brain (necrosis, apoptosis and delayed neuronal death) are reviewed, with an emphasis on gene regulation of naturally-occurring and HI-associated cell death. We report the expression of the immediate early gene c-fos and c-jun mRNAs and of HSP72 mRNA and protein in several models of cerebral HI. Gel agarose electrophoresis of extracted DNA and in situ end-labeling of fragmented DNA revealed that cell death in these models was associated with endonuclease(s) activation. We also pre-treated some animals with dexamethasone, a neuroprotective drug in a model of perinatal HI. High-dose dexamethasone prevented c-fos induction in cerebral regions sensitive to HI. This effect may be due to a functional antagonism, at the transcriptional level, between Fos and the glucocorticoid receptor.

Animals↗