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139 results on '"Canudas, A. M."'

14. A Novel NMDA Receptor Antagonist Protects against Cognitive Decline Presented by Senescent Mice

Author

Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica, Companys Alemany, Júlia, Turcu, Andreea L., Bellver Sanchis, Aina, Loza García, María Isabel, Brea Floriani, José Manuel, Canudas, Anna M., Leiva, Rosana, Vázquez, Santiago, Pallàs, Mercè, Griñán Ferré, Christian, Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica, Companys Alemany, Júlia, Turcu, Andreea L., Bellver Sanchis, Aina, Loza García, María Isabel, Brea Floriani, José Manuel, Canudas, Anna M., Leiva, Rosana, Vázquez, Santiago, Pallàs, Mercè, and Griñán Ferré, Christian

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia. Non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist memantine improved cognition and molecular alterations after preclinical treatment. Nevertheless, clinical results are discouraging. In vivo efficacy of the RL-208, a new NMDA receptor blocker described recently, with favourable pharmacokinetic properties was evaluated in Senescence accelerated mice prone 8 (SAMP8), a mice model of late-onset AD (LOAD). Oral administration of RL-208 improved cognitive performance assessed by using the three chamber test (TCT), novel object recognition test (NORT), and object location test (OLT). Consistent with behavioural results, RL-208 treated-mice groups significantly changed NMDAR2B phosphorylation state levels but not NMDAR2A. Calpain-1 and Caspase-3 activity was reduced, whereas B-cell lymphoma-2 (BCL-2) levels increased, indicating reduced apoptosis in RL-208 treated SAMP8. Superoxide Dismutase 1 (SOD1) and Glutathione Peroxidase 1 (GPX1), as well as a reduction of hydrogen peroxide (H2O2), was also determined in RL-208 mice. RL-208 treatment induced an increase in mature brain-derived neurotrophic factor (mBDNF), prevented Tropomyosin-related kinase B full-length (TrkB-FL) cleavage, increased protein levels of Synaptophysin (SYN) and Postsynaptic density protein 95 (PSD95). In whole, these results point out to an improvement in synaptic plasticity. Remarkably, RL-208 also decreased the protein levels of Cyclin-Dependent Kinase 5 (CDK5), as well as p25/p35 ratio, indicating a reduction in kinase activity of CDK5/p25 complex. Consequently, lower levels of hyperphosphorylated Tau (p-Tau) were found. In sum, these results demonstrate the neuroprotectant role of RL-208 through NMDAR blockade

Published
2020

28. Erratum: Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells (Cell Death and Differentiation (2005) vol. 12 (1124-1038) 10.1038/sj.cdd4401752)

Author

Di Giorgi-Gerevini, Valeria, Melchiorri, D., Battaglia, G., Ricci-Vitiani, L., Ciceroni, C., Busceti, C. L., Biagioni, F., Iacovelli, L., Canudas, A. M., Parati, E., De Maria Marchiano, Ruggero, and Nicoletti, F.

Subjects
Settore MED/04 - PATOLOGIA GENERALE, Cell Biology
Published
2005

30. Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

Author

Di Giorgi-Gerevini, Valeria, Melchiorri, D., Battaglia, G., Ricci-Vitiani, L., Ciceroni, C., Busceti, C. L., Biagioni, F., Iacovelli, L., Canudas, A. M., Parati, E., De Maria Marchiano, Ruggero, Nicoletti, F., De Maria, R. (ORCID:0000-0003-2255-0583), Di Giorgi-Gerevini, Valeria, Melchiorri, D., Battaglia, G., Ricci-Vitiani, L., Ciceroni, C., Busceti, C. L., Biagioni, F., Iacovelli, L., Canudas, A. M., Parati, E., De Maria Marchiano, Ruggero, Nicoletti, F., and De Maria, R. (ORCID:0000-0003-2255-0583)

Abstract

The use of neural progenitor cells (NPCs) is limited by the incomplete knowledge of the extracellular signals regulating their proliferation and survival. We report that cultured mouse NPCs express functional mGlu3 and mGlu5 metabotropic glutamate receptors. Pharmacological blockade of both receptors reduced NPC proliferation and survival, whereas activation of mGlu5 receptors substantially enhanced cell proliferation. Adult mice lacking mGlu5 receptors or treated with mGlu5 or mGlu3 receptor antagonists showed a dramatic reduction in the number of dividing neuroprogenitors present in the subventricular zone and in the dentate gyrus of the hippocampus. These data disclose a novel function of mGlu receptors and offer new potential strategies for the optimization of cell replacement therapy in neurodegenerative disorders. © 2005 Nature Publishing Group. All rights reserved.

Published
2005

34. Enhanced Tau Phosphorylation in the Hippocampus of Mice Treated with 3,4-Methylenedioxymethamphetamine ("Ecstasy")

Author

Busceti, C. L., primary, Biagioni, F., additional, Riozzi, B., additional, Battaglia, G., additional, Storto, M., additional, Cinque, C., additional, Molinaro, G., additional, Gradini, R., additional, Caricasole, A., additional, Canudas, A. M., additional, Bruno, V., additional, Nicoletti, F., additional, and Fornai, F., additional

Published
2008
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35. Erratum: Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

Author

Di Giorgi-Gerevini, V, primary, Melchiorri, D, additional, Battaglia, G, additional, Ricci-Vitiani, L, additional, Ciceroni, C, additional, Busceti, C L, additional, Biagioni, F, additional, Iacovelli, L, additional, Canudas, A M, additional, Parati, E, additional, DeMaria, R, additional, and Nicoletti, F, additional

Published
2005
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46. Metabotropic glutamate receptors and neuroadaptation to antidepressants: imipramine-induced down-regulation ofβ-adrenergic receptors in mice treated with metabotropic glutamate 2/3 receptor ligands.

Author

Matrisciano, F., Scaccianoce, S., del Bianco, P., Panaccione, I., Canudas, A. M., Battaglia, G., Riozzi, B., Ngomba, R. T., Molinaro, G., Tatarelli, R., Melchiorri, D., and Nicoletti, F.

Subjects
ADRENERGIC receptors, ANTIDEPRESSANTS, PSYCHIATRIC drugs, IMIPRAMINE, DRUG receptors, SYMPATHETIC nervous system
Abstract

Antidepressant drugs have a clinical latency that correlates with the development of neuroadaptive changes, including down-regulation ofβ-adrenergic receptors in different brain regions. The identification of drugs that shorten this latency will have a great impact on the treatment of major depressive disorders. We report that the time required for the antidepressant imipramine to reduce the expression ofβ-adrenergic receptors in the hippocampus is reduced by a co-administration with centrally active ligands of type 2/3 metabotropic glutamate (mGlu2/3) receptors. Daily treatment of mice with imipramine alone (10 mg/kg, i.p.) reduced the expression ofβ-adrenergic receptors in the hippocampus after 21 days, but not at shorter times, as assessed by western blot analysis ofβ1-adrenergic receptors and by the amount of specifically bound[3H]CGP-12177, a selectiveβ-adrenergic receptor ligand. Down-regulation ofβ-adrenergic receptors occurred at shorter times (i.e. after 14 days) when imipramine was combined with low doses (0.5 mg/kg, i.p.) of the selective mGlu2/3 receptor agonist LY379268, or with the preferential mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.). Higher doses of LY379268 (2 mg/kg, i.p.) were inactive. This intriguing finding suggests that neuroadaptation to imipramine– at least as assessed by changes in the expression ofβ1-adrenergic receptors– is influenced by drugs that interact with mGlu2/3 receptors and stimulates further research aimed at establishing whether any of these drugs can shorten the clinical latency of classical antidepressants. [ABSTRACT FROM AUTHOR]

Published
2005
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47. (±)-huprine Y, (-)-huperzine A and tacrine do not show neuroprotective properties in an apoptotic model of neuronal cytoskeletal alteration.

Author

Jordá, E. G., Verdaguer, E., Jiménez, A., Canudas, A. M., Rimbau, V., Camps, P., Muñoz-Torrero, D., Camins, A., and Pallàs, M.

Subjects
ACETYLCHOLINESTERASE, CHEMICAL inhibitors, ALZHEIMER'S disease, COLCHICINE, APOPTOSIS, NEURONS
Abstract

Acetylcholinesterase inhibitors (AChEI) are among the drugs most widely used in the treatment of Alzheimer's disease. They increase the levels of acetylcholine and thus improve the cognitive symptoms that are impaired. We tested whether specific AChEI show additional neuroprotective properties against colchicine-induced apoptosis in cerebellar granule neurons (CGNs), a well established apoptotic model mediated by neuronal cytoskeleton alteration. Colchicine-induced apoptosis is due to an increase in the activity of GSK-3β and CDK5, two enzymes involved in cytoskeletal alteration. Furthermore, the intrinsic apoptotic pathway is activated by colchicines, as revealed by cytochrome c release and Bax translocation. Tacrine, (-)-huperzine A and (±)-huprine Y, the AChEI tested in the study, did not reverse the loss of neuronal viability induced by colchicine. Moreover, the increase in apoptotic features induced by colchicine treatment, as measured by flow cytometry and nuclear chromatin condensation, was not prevented by these AChEI. Although some of these drugs are of interest to treat Alzheimer's disease, their lack of efficacy in the prevention of colchicine-induced apoptosis in CGNs suggests that they cannot prevent neuronal loss due to cytoskeleton alteration. [ABSTRACT FROM AUTHOR]

Published
2004

48. Inhibition of CDKs: A Strategy for Preventing Kainic Acid--Induced Apoptosis in Neurons.

Author

VERDAGUER, E, JORDÀ, ELVIRA G., STRANGES, ALESSANDRA, CANUDAS, ANNA M., JIMÉNEZ, ANDRÉS, SUREDA, FRANCESC X., PALLÀS, MERCÈ, and CAMINS, ANTONI

Subjects
NEURONS, APOPTOSIS, ALZHEIMER'S disease, NEURODEGENERATION, PROTEINS, NEUROTOXIC agents, CELL death, AMINO acids, NERVOUS system
Abstract

Stimulation of ionotropic glutamate receptors are implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Recently this has been demonstrated in the expression of cell cycle proteins in vulnerable neurons in Alzheimer's disease. Thus, the aim of the present study was to evaluate the expression of cell cycle proteins in cerebellar granule cells after stimulation of AMPA/KA receptors and likewise to study the neuroprotective effects of CDK inhibitors. Our results demonstrated that after a treatment with CDK inhibitors, a significant decrease in apoptotic nuclei induced by kainic acid was found in the presence of flavopiridol and 3-ATA. We concluded that CDK activation is involved, at least, in part, in the pro-apoptotic effects of kainic acid. [ABSTRACT FROM AUTHOR]

Published
2004
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50. Inhibitors of Cyclin-Dependent Kinases: Potential Drugs for the Treatment of Neurodegenerative Disorders?

Author

Pallas, Merce, Canudas, Anna M., Verdaguer, Ester, Allgaier, Clemens, de Arriba, Susana Garcia, Alvira, Daniel, Sureda, Francesc X., and Camins, Antoni

Abstract

The pharmacological treatment of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) currently represents a major medical challenge. The mechanisms involved in the apoptotic neuronal cell death, associated with such disorders, are still not clear, but recent data suggest that cyclindependent kinases (CDKs) play a prominent role (Liu et al., 2003). Canonical CDKs such as CDK2 and CDK4/CDK6 are enzymes associated with cyclin regulatory subunits that control cell cycle progression. The evidence that neurons in postmortem brain tissue from patients with neurodegenerative diseases express CDKs, supports to the hypothesis that re-entry into the cell cycle could be an apoptotic pathway involved in the neurodegenerative process. Several authors suggest that the transcription factor E2F-1 function as a link between the cell cycle and apoptosis in neurons. Additionally the expression of CDK5 has been demonstrated in postmortem brain tissue from patients with neurodegenerative diseases. CDK5 is an atypical CDK, that does not require association with a cyclin and is not implicated in the cell cycle progression. Instead, it is associated with the neuronal co-activators p35 and p39, and is required for neuronal development, axonal outgrowth, learning and memory. Recent evidence also points to a leading role for CDK5/p25 in apoptosis and neurodegeneration. CDK inhibitors such as flavopiridol and roscovitine are being developed and tested in clinical trials as novel antineoplasic agents. Thus, due to the implication of CDKs in neuronal apoptosis, a new application of these drugs in the treatment of neurodegenerative diseases is suggested.

Published
2005

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