Publications by authors named "Stefania Pirondi"

7 Publications

  • Page 1 of 1

Neurotensin receptor involvement in the rise of extracellular glutamate levels and apoptotic nerve cell death in primary cortical cultures after oxygen and glucose deprivation.

Cereb Cortex 2008 Aug 5;18(8):1748-57. Epub 2007 Dec 5.

Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, 44100 Ferrara, Italy.

In view of the ability of neurotensin (NT) to increase glutamate release, the role of NT receptor mechanisms in oxygen-glucose deprivation (OGD)-induced neuronal degeneration in cortical cultures has been evaluated by measuring lactate dehydrogenase (LDH) levels, mitochondrial dehydrogenase activity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide levels, and microtubule-associated protein 2 (MAP2) immunoreactivity. Apoptotic nerve cell death was analyzed measuring chromatin condensation with Hoechst 33258, annexin V staining, and caspase-3 activity. Furthermore, the involvement of glutamate excitotoxicity in the neurodegeneration-enhancing actions of NT was analyzed by measurement of extracellular glutamate levels. NT enhanced the OGD-induced increase of LDH, endogenous extracellular glutamate levels, and apoptotic nerve cell death. In addition, the peptide enhanced the OGD-induced loss of mitochondrial functionality and increase of MAP2 aggregations. These effects were blocked by the neurotensin receptor 1 (NTR1) antagonist SR48692. Unexpectedly, the antagonist at 100 nM counteracted not only the NT effects but also some OGD-induced biochemical and morphological alterations. These results suggest that NTR1 receptors may participate in neurodegenerative events induced by OGD in cortical cultures, used as an in vitro model of cortical ischemia. The NTR1 receptor antagonists could provide a new tool to explore the clinical possibilities and thus to move from chemical compound to effective drug.
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http://dx.doi.org/10.1093/cercor/bhm217DOI Listing
August 2008

Prenatal glucocorticoid exposure affects learning and vulnerability of cholinergic neurons.

Neurobiol Aging 2007 Jan 6;28(1):112-21. Epub 2006 Jan 6.

Department of Veterinary Morphophysiology and Animal Production, University of Bologna, 40064 Ozzano Emilia Bologna, Italy.

Prenatal treatment with synthetic glucocorticoids is commonly used as a treatment for women at risk of preterm delivery. However, little is known about the life-long consequences of these treatments on the fetus. In the present study, we evaluated cognitive function as well as susceptibility of cholinergic neurons to (192)IgG-saporin immunolesion in adult rats after prenatal glucocorticoid treatment. Morris water maze results revealed a significant difference in learning and memory function in adult rats that were prenatally exposed to dexamethasone, and further cognitive deficits after (192)IgG-saporin exposure. Choline acetyl transferase activity was decreased in the cortex of dexamethasone-treated rats compared with controls. In addition, rats prenatally exposed to either dexa, or betamethasone revealed a dramatic decrease in choline acetyl transferase activity compared to control rats after (192)IgG-saporin lesion. We report behavioral and biochemical evidence for altered cognitive function and increased susceptibility of cholinergic neurons to (192)IgG-saporin in adult rats after prenatal glucocorticoid treatment. Taken together, these results suggest that prenatal treatment with dexamethasone could affect cognitive functions and render cholinergic neurons more vulnerable to challenges later in life.
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http://dx.doi.org/10.1016/j.neurobiolaging.2005.11.015DOI Listing
January 2007

The galanin-R2 agonist AR-M1896 reduces glutamate toxicity in primary neural hippocampal cells.

J Neurochem 2005 Nov 31;95(3):821-33. Epub 2005 Aug 31.

Department of Veterinary Morphophysiology and Animal Production, University of Bologna, Bologna, Italy.

Galanin is a neuropeptide involved in a variety of biological functions, including having a strong anticonvulsant activity. To assess a possible role of galanin in modulation of glutamatergic synapses and excitotoxicity, we studied effects of a galanin receptor 2(3) agonist (AR-M1896) on several molecular events induced by glutamate administration in primary neural hippocampal cells. Exposure of cells, after 5 days in vitro, to glutamate 0.5 mM for 10 min caused morphological alterations, including disaggregation of beta-tubulin and MAP-2 cytoskeletal protein assembly, loss of neurites and cell shrinkage. When present in culture medium together with glutamate, 1 and 10 nM of AR-M1896 reduced these alterations. Moreover, AR-M1896 counteracted glutamate-induced c-fos mRNA and c-Fos protein up-regulation after 30-150 min, and 24 h, respectively. Massive nuclear alterations (Hoechst 33258 staining), observed 24 h after glutamate exposure, were also antagonized by AR-M1896 (0.1-100 nM) in a dose-dependent manner. These findings indicate that galanin, probably mainly through its type 2 receptor, interferes with events associated with glutamate toxicity.
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http://dx.doi.org/10.1111/j.1471-4159.2005.03437.xDOI Listing
November 2005

Thyroid hormone and remyelination in adult central nervous system: a lesson from an inflammatory-demyelinating disease.

Brain Res Brain Res Rev 2005 Apr 26;48(2):339-46. Epub 2005 Jan 26.

Department of Veterinary Morphophysiology and Animal Production, University of Bologna, Italy.

Re-myelination in the adult CNS has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that re-myelination is effective in multiple sclerosis (MS), the most diffuse demyelinating disease. Moreover, chronic disabilities in MS are believed to be due to remyelination failure and consequent neuron damage and degeneration. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, reasons for remyelination failure are unknown. In this paper, we reviewed data from embryonic development and in vitro studies supporting the primary role of thyroid hormone in oligodendrocyte maturation. We also reviewed personal data on the possibility of promoting myelination in chronic experimental allergic encephalomyelitis (EAE), a widely used experimental model of MS, by recruiting progenitors and channeling them into oligodendroglial lineage through the administration of thyroid hormone.
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http://dx.doi.org/10.1016/j.brainresrev.2004.12.022DOI Listing
April 2005

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease.

Proc Natl Acad Sci U S A 2004 Nov 8;101(46):16363-8. Epub 2004 Nov 8.

Department of Veterinary Morphophysiology and Animal Production, University of Bologna, 40064 Ozzano Emilia, Bologna, Italy.

Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.e., experimental allergic encephalomyelitis in congenic female Dark Agouti rats immunized with complete guinea pig spinal cord. Thyroid hormone, when administered during the acute phase of the disease, increases expression of platelet-derived growth factor alpha receptor, restores normal levels of myelin basic protein mRNA and protein, and allows an early and morphologically competent reassembly of myelin sheaths. Moreover, thyroid hormone exerts a neuroprotective effect with respect to axonal pathology.
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http://dx.doi.org/10.1073/pnas.0407262101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC526198PMC
November 2004

Stem cells and nervous tissue repair: from in vitro to in vivo.

Prog Brain Res 2004 ;146:75-91

Department of Veterinary Morphophysiology and Animal Production (DIMORFIPA), University of Bologna, Bologna, Italy.

Recent development in stem cell biology has indicated a new possible approach for the treatment of neurological diseases. However, in spite of tremendous hope generated, we are still on the way to understand if the use of stem cells to repair mature brain and spinal cord is a reliable possibility. In particular, we know very little on the in situ regulation of adult neural stem, and this also negatively impact on cell transplant possibilities. In this chapter we will discuss issues concerning the role and function of stem cells in neurological diseases, with regard to the impact of features of degenerating neurons and glial cells on in situ stem cells. Stem cell location and biology in the adult brain, brain host reaction to transplantation, neural stem cell reaction to experimental injuries and possibilities for exogenous regulation are the main topics discussed.
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http://dx.doi.org/10.1016/s0079-6123(03)46005-6DOI Listing
February 2004

Neural stem cells and cholinergic neurons: regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor.

Proc Natl Acad Sci U S A 2003 Jun 30;100(12):7325-30. Epub 2003 May 30.

Department of Veterinary Morphophysiology and Animal Production, University of Bologna, 40064 Ozzano Emilia (Bologna), Italy.

Degenerative diseases represent a severe problem because of the very limited repair capability of the nervous system. To test the potential of using stem cells in the adult central nervous system as "brain-marrow" for repair purposes, several issues need to be clarified. We are exploring the possibility of influencing, in vivo, proliferation, migration, and phenotype lineage of stem cells in the brain of adult animals with selective neural lesions by exogenous administration (alone or in combination) of hormones, cytokines, and neurotrophins. Lesion of the cholinergic system in the basal forebrain was induced in rats by the immunotoxin 192IgG-saporin. Alzet osmotic minipumps for chronic release (over a period of 14 days) of mitogens [epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF)] were implanted in animals with behavioral and biochemical cholinergic defect and connected to an intracerebroventricular catheter. After 14 days of delivery, these pumps were replaced by others delivering nerve growth factor (NGF) for an additional 14 days. At the same time, retinoic acid was added to the rats' food pellets for one month. Whereas the lesion decreased proliferative activity, EGF and bFGF both increased the number of proliferating cells in the subventricular zone in lesioned and nonlesioned animals. These results are indicated by the widespread distribution of BrdUrd-positive nuclei in the forebrain, including in the cholinergic area. Performance in the water maze test was improved in these animals and choline acetyltransferase activity in the hippocampus was increased. These results suggest that pharmacological control of endogenous neural stem cells can provide an additional opportunity for brain repair. These studies also offer useful information for improving integration of transplanted cells into the mature brain.
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http://dx.doi.org/10.1073/pnas.1132092100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165874PMC
June 2003