El nostre principal objectiu científic és investigar en models experimentals i en patologies degeneratives humanes els mecanismes moleculars i cel·lulars de inducció i prevenció de la mort neuronal. Els nostres resultats descriuen alguns mecanismes cel·lulars d’adaptació als processos neurodegeneratius. Així hem trobat que el procés de calcificació pot interpretar-se com un mecanisme general d'adaptació cel·lular per tal de reduïr el dany cerebral.
Recentment hem trobat en un model murí d’esclerosi múltiple, i en el model de lesion excitotòxica a l’hipocamp de la rata que l'activació crónica del canal KATP microglial disminueix l’activitat pro-inflamatòria de la micròglia, la qual cosa implica una reducció del dany neuronal i un enlentiment del process neurodegeneratiu engegat. També hem demostrat que el canal KATP té un paper central en el control de la reacció microglial que segueix a l’isquemia en rates tMCAo i hem identificat la micròglia com un potent regulador de la supervivència neuronal en les primeres fases de l’ictus cerebral.
Bosch MN, Pugliese M, Gimeno–Bayón J, Rodríguez MJ, Mahy N. (2012) “Dogs with cognitive dysfunction syndrome: a natural model of Alzheimer’s disease“ Curr Alzheimer Res (en premsa).
Virgili N, Espinosa–Parrilla JF, Mancera P, Pasten–Zamorano A, Gimeno–Bayón J, Rodríguez MJ, Mahy N, Pugliese M. (2011) “Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis“ J Neuroinflamm 8:149 (Baixar-ho)
Gonzalo-Ruiz A, Delso M, Carrero I, Gonzalo-Vicente P, Sanz–Anquela JM, Rodríguez MJ, Arévalo–Serrano J. (2011) “A rat model of oligomeric forms of beta-amyloid (Aβ) peptide: neuronal loss, synaptic alteration, astrogliosis, and calcium-binding proteins activation in vivo“ Eur J Anat 15:47–72
Vidal–Taboada JM, Mahy N and Rodríguez MJ. (2011) “Microglia, calcification and Neurodegenerative Diseases“ cap 13 in Neurodegenerative Diseases – Processes, Prevention, Protection and Monitoring. p. 301–322. Ed. Chuen–Chung Chang. InTech, Rijeka. (Baixar-ho)
Pugliese M, Carrasco JL, Gómez-Ansón B, Andrade C, Zamora A, Rodríguez MJ, Mascort J, and Mahy N. (2010) “Magnetic resonance imaging of cerebral involutional changes in dogs as markers of aging: An innovative tool adapted from a human visual rating scale” Vet J 186:166–171
Pugliese M, Rodríguez MJ, Gimeno-Bayon J, Pujadas L, Billett EE, Wells C, Mahy N. (2010) Alzheimer's disease modifies progenitor cell expression of monoamine oxidase B in the subventricular zone. J Neurosci Res. 88(12):2588-97.
Pérez JL, Carrero I, Gonzalo P, Arevalo-serrano J, Sanz-Anquela JM, Ortega J, Rodríguez MJ, and Gonzalo-Ruíz A. (2010) “Soluble oligomeric forms of beta-amyloid (Aβ) peptide stimulate Aβ production via astrogliosis in the rat brain” Exp Neurol 223:410-421
Fernández LJ, Altuna A, Tijeroa M, Gabriel G, Villa G, Rodríguez MJ, Batlle M, Vilaresa R, Berganzoa J, Blanco FJ. (2009) “Study of functional viability of SU-8-based microneedles for neural applications” J Micromech Microeng 19:025007.
Bernal F, Petegnief V, Rodríguez MJ, Ursu G, Pugliese M, Mahy N.(2009) Nimodipine inhibits TMB-8 potentiation of AMPA-induced hippocampal neurodegeneration. J Neurosci Res. 87(5):1240-9.
Rodríguez MJ, Prats A, Malpesa Y, Andrés N, Pugliese M, Batlle M, Mahy N. (2009) Pattern of injury with a graded excitotoxic insult and ensuing chronic medial septal damage in the rat brain. J Neurotrauma. 26(10):1823-34.
Rodríguez MJ, Pugliese M, Mahy N. (2009) Drug abuse, brain calcification and glutamate-induced neurodegeneration. Curr Drug Abuse Jan;2(1):99-112. Review.
Pugliese M, Gangitano C, Ceccariglia S, Carrasco JL, DEl Fà A, Rodríguez
MJ, Michetti F, Mascort J, Mahy N.(2007) Canine cognitive dysfunction
and the cerebellum acetylcholinesterase reduction, neuronal and glial
changes. Brain Res 1139:85-94
Rodríguez MJ, Pugliese M, Mahy N.(2007) KATP channel
modulates micrologia activity and neuronal loss Glial Cells in Health
and Disease: The VII European meeting (International Proceedings) . 125-129
Pugliese M, Rodríguez MJ, Carrasco JL, Ferrer I, Michetti F, Mascort J,
Mahy N.(2007) Canine model of senile dementia: sponttaneous
presence of Alzheimer's disease markers. Glial Cells in Health and
Disease: The European Meeting (International Proceedings) . 125-129
de Yebra Ll., Malpesa Y., Ursu G., Pugliese M., Liévens JC., Kerkerian-le Goff L.,
and Mahy N. (2006) Dissociation between hippocampal neuronal loss, astroglial and microglial reactivity after pharmacologically induced reverse glutamate transport. Neurochem Int. 49:691-697.
Pugliese M, Mascort J, Mahy N, and Ferrer I (2006) Diffuse beta-amyloid plaques and hyperphosphorylated tau are unrelated processes in aged dogs with behavioral deficits. Acta Neuropathol. 112:175–183.
Pugliese M., Geloso MC., Carrasco JL., Mascort J., Michetti F., and Mahy N. (2006) Canine cognitive deficit correlates with diffuse plaque maturation and S100b(-) astrocytosis but not with insulin cerebrospinal fluid level Acta Neuropathol. 111: 519–528
Ramonet D., de Yebra Ll., Fredriksson K., Bernal F., Ribalta T., and Mahy N. (2006) Similar calcification process in acute and chronic human brain pathologies J. Neurosci. Res. 83:147-156.
Rodríguez MJ., Robledo P., Andrade C., and Mahy N. (2005) In vivo co-ordinated interactions between inhibitory systems to control glutamate mediated hippocampal excitability J. Neurochem. 91:651-661.
Pugliese M., Carrasco JL., Andrade C., Mas E., Mascort J., and Mahy N. (2005) Severe cognitive impairment correlates with higher cerebrospinal fluid levels of lactate and pyruvate in a canine model of senile dementia Prog. Neuro-Psychophar. & Biol. Psych. 29:603-610.
