Researh & development

Laboratory of Neurobiology of Aging

Profile

Synaptic mitochondrial dysfunction and memory loss in aging

One of the areas of the brain most affected by aging is the hippocampus, a crucial structure in learning and memory processes. My laboratory studies the changes that hippocampal mitochondria undergo in aging, specifically those found in synapses, which correspond to areas of neuronal communication. Synaptic mitochondria are more vulnerable to damage than non-synaptic mitochondria. We are investigating structural and functional differences in synaptic mitochondria that explain this vulnerability and their contribution to age-related memory loss, with particular emphasis on the mitochondrial protease Lonp1. We also studied factors that promote mitochondrial dysfunction, including the accumulation of phosphorylated tau (Ser396-Ser404: PHF-1) in mitochondria, a microtubule-associated protein that, upon phosphorylation, loses its function. Another aspect that we explore is the possible anti-aging effect of molecules that improve mitochondrial function. We used in vitro and in vivo models, including primary mouse hippocampal neuron culture, organotypic culture, and the accelerated senescence-prone or normally aged mouse (SAMP8).

Research Head   

Dr. Cheril Tapia Rojas

Doctoral Students   

  • Jesús Llanquinao Sandoval (co-tutor: Dr Bredford Kerr) 
  • Angie Torres Juacida (Co-tutor, Tutor: Dr Nibaldo Inestrosa) 
  • Nuria Llontop López (Co-tutor, tutor: Dr. Bredford Kerr) 
  • Daniela Cortés 
  • Nicole Diaz (co-tutor: Dr Alfonso Gonzalez)

Undergraduate Students

  • Karina Villalobos Cicali 
  • Fernanda Maturana 
  • Claudia Narea 

Research Assistants     

  • Gloria Mendez Díaz 
  • Alejandra Catenaccio 
  • Maira Pizarro

Post-doctoral Fellows   

  • Dr. Claudia Jara Orellana 
  • Dr. Matías Lira Mendieta 

Research Post-doctoral

Dr. Matias Lira Mendieta

  • Dra. Claudia Jara, Former Post-Doc, 2018-2023, Universidad San Sebastián, Chile
  • Catalina Meléndez Polanco, Former Ph.D. student, 2017-2023 (co-tutor: Dr. Gonzalo Mardones)
  • Diego Tapia Zamorano, Former Ph.D. student, 2017-2022 (co-tutor, tutor: Dr. Jorge Cancino)
  • Camila Vega, Former Medical Technologist student, 2023, Universidad San Sebastián, Chile
  • Carolina Butti, Former Medical Technologist student, 2023, Universidad San Sebastián, Chile
  • Italo Fuentes Poblete, Former Medical Technologist student, 2022, Universidad San Sebastián, Chile
  • Luis Gonzalez Ortega, Former Medical Technologist student, 2022, Universidad San Sebastián, Chile
  • Daniela Cortés Díaz, Former Biochemistry student, 2022-2023, Universidad San Sebastián, Chile
  • Han Sol Park, Former Biochemistry student, 2019-2021, Pontificia Universidad Católica de Chile, Chile
  • Bastián Rivera Puebla, Former Biochemistry student, 2020-2021, Universidad San Sebastián, Chile
  • Margrethe Olesen Arancibia, Former Master in Neuroscience student, 2018-2019, Universidad Autónoma de Chile, Chile.
  • Fabián Alarcón Illesca, Former Master in Neuroscience student, 2018-2020, Universidad Autónoma de Chile, Chile.
  • Gabriela Vargas Mardones, Former Ph.D. student, 2017-2022 (Co-tutor, tutor: Dr. Patricia Burgos)

National Collaborations

  • Dr (c) Débora Buendía Palacios, Universidad de Valparaíso
  • Dr. Pablo Muñoz, Universidad de Valparaíso
  • Dr. Nibaldo Inestrosa Cantín, Pontificia Universidad Católica de Chile
  • Dr. Andreas Schueller, Pontificia Universidad Católica de Chile
  • Dr. Alfonso Gonzalez de la Rosa, Universidad San Sebastián
  • Dr. Bredford Kerr, Universidad San Sebastián
  • Dr. Patricia Burgos, Universidad San Sebastián
  • Dr. Jorge Cancino, Universidad San Sebastián

Internationals Collaborations

  • Dr. Michael P. Murphy, University of Cambridge, Cambridge, UK
  • Dr. Marcello Pinti, University of Modena and Reggio Emilia, Italy

Publications

Inestrosa NC, Tapia-Rojas C, Griffith TN, Carvajal FJ, Benito MJ, Rivera-Dictter A, Alvarez AR, Serrano FG, Hancke JL, Burgos PV, Parodi J, Varela-Nallar L. Transl Psychiatry. 2011 Jul 12;1:e20. doi: 10.1038/tp.2011.19.Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer’s disease: a possible effect on APP processing.

Ardiles AO, Tapia-Rojas CC, Mandal M, Alexandre F, Kirkwood A, Inestrosa NC, Palacios AG. Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13835-40. doi: 10.1073/pnas.1201209109. Epub 2012 Aug 6.Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer’s disease.

Carvajal FJ, Zolezzi JM, Tapia-Rojas C, Godoy JA, Inestrosa NC. J Alzheimers Dis. 2013 Jan 1;36(1):99-118. doi: 10.3233/JAD-130230. Tetrahydrohyperforin Decreases Cholinergic Markers associated with Amyloid-β Plaques, 4-Hydroxynonenal Formation, and Caspase-3 Activation in AβPP/PS1 Mice.

Inestrosa NC, Carvajal FJ, Zolezzi JM, Tapia-Rojas C, Serrano F, Karmelic D, Toledo EM, Toro A, Toro J, Santos MJ. J Alzheimers Dis. 2013;33(4):941-59. doi: 10.3233/JAD-2012-120397.Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer’s disease

Viayna E, Sola I, Bartolini M, De Simone A, Tapia-Rojas C, Serrano FG, Sabaté R, Juárez-Jiménez J, Pérez B, Luque FJ, Andrisano V, Clos MV, Inestrosa NC, Muñoz-Torrero D. J Med Chem. 2014 Mar 27;57(6):2549-67. doi: 10.1021/jm401824w. Epub 2014 Mar 10.Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents.

Serrano FG, Tapia-Rojas C, Carvajal FJ, Hancke J, Cerpa W, Inestrosa NC. Mol Neurodegener. 2014 Dec 18;9:61. doi: 10.1186/1750-1326-9-61.Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice.

Inestrosa NC, Ríos JA, Cisternas P, Tapia-Rojas C, Rivera DS, Braidy N, Zolezzi JM, Godoy JA, Carvajal FJ, Ardiles AO, Bozinovic F, Palacios AG, Sachdev PS. Brain Pathol. 2015 Nov;25(6):679-91. doi: 10.1111/bpa.12226. Epub 2015 Feb 10.Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus, a Natural Model of Alzheimer’s Disease.

Cavieres VA, González A, Muñoz VC, Yefi CP, Bustamante HA, Barraza RR, Tapia-Rojas C, Otth C, Barrera MJ, González C, Mardones GA, Inestrosa NC, Burgos PV. PLoS One. 2015 Aug 26;10(8):e0136313. doi: 10.1371/journal.pone.0136313. eCollection 2015.Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy.

Du LY, Chang LY, Ardiles AO, Tapia-Rojas C, Araya J, Inestrosa NC, Palacios AG, Acosta ML. PLoS One. 2015 Aug 12;10(8):e0135499. doi: 10.1371/journal.pone.0135499. eCollection 20Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus.

Cuevas CA, Tapia-Rojas C, Cespedes C, Inestrosa NC, Vio CP. Biomed Res Int. 2015;2015:726012. doi: 10.1155/2015/726012. Epub 2015 Apr 7.β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats.

Serrano FG, Tapia-Rojas C, Carvajal FJ, Cisternas P, Viayna E, Irene S, Muñoz-Torrero D, Inestrosa NC. Curr Alzheimer Res. 2015 Oct 27. [Epub ahead of print]Rhein-huprine derivatives reduce cognitive impairment, synaptic failure and amyloid pathology in AβPPswe/PS-1 mice of different ages.

Fuenzalida M, Espinoza C, Pérez MÁ, Tapia-Rojas C, Cuitino L, Brandan E, Inestrosa NC. Neurobiol Dis. 2016 Feb;86:109-20. doi: 10.1016/j.nbd.2015.11.018. Epub 2015 Dec 2. Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy.

Varela-Nallar L, Arredondo SB, Tapia-Rojas C, Hancke J, Inestrosa NC. Neural Plast. 2015;2015:935403. doi: 10.1155/2015/935403. Epub 2015 Dec 22.Andrographolide Stimulates Neurogenesis in the Adult Hippocampus.

Tapia-Rojas C, Schüller A, Lindsay CB, Ureta RC, Mejías-Reyes C, Hancke J, Melo F, Inestrosa NC. Biochem J. 2015 Mar 1;466(2):415-30. doi: 10.1042/BJ20140207.Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3β in vivo.

Tapia-Rojas C, Lindsay CB, Montecinos-Oliva C, Arrazola MS, Retamales RM, Bunout D, Hirsch S, Inestrosa NC. Mol Neurodegener. 2015 Nov 21;10:62. doi: 10.1186/s13024-015-0057-0.Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice.

Tapia-Rojas C, Aranguiz F, Varela-Nallar L, Inestrosa NC. Brain Pathol. 2016 Jan;26(1):62-74. doi: 10.1111/bpa.12255. Epub 2015 May 7.Voluntary Running Attenuates Memory Loss, Decreases Neuropathological Changes and Induces Neurogenesis in a Mouse Model of Alzheimer’s Disease

Tapia-Rojas C, Burgos PV, Inestrosa NC. J Neurochem. 2016 Dec;139(6):1175-1191. doi: 10.1111/jnc.13873.Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid-β (Aβ)42 peptides.

Quintanilla RA, Tapia C, Pérez MJ. Biochem Biophys Res Commun. 2017 Feb 19;483(4):1078-1083. doi: 10.1016/j.bbrc.2016.09.054. Epub 2016 Sep 13. Review.Possible role of mitochondrial permeability transition pore in the pathogenesis of Huntington disease

Tapia-Rojas C, Mira RG, Torres AK, Jara C, Pérez MJ, Vergara EH, Cerpa W, Quintanilla RA. Birth Defects Res. 2017 Dec 1;109(20):1623-1639. doi: 10.1002/bdr2.1172. Review.Alcohol consumption during adolescence: A link between mitochondrial damage and ethanol brain intoxication

Tapia-Rojas C, Carvajal FJ, Mira RG, Arce C, Lerma-Cabrera JM, Orellana JA, Cerpa W, Quintanilla RA. Mol Neurobiol. 2018 May;55(5):4473-4491. doi: 10.1007/s12035-017-0613-4. Epub 2017 Jun 1.Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment

Tapia-Rojas C, Inestrosa NC. J Neurochem. 2018 Feb;144(4):443-465. doi: 10.1111/jnc.14278. Epub 2018 Jan 26.Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer’s disease in J20-APP transgenic and wild-type mice

Claudia Jara, Alejandra Aránguiz, Waldo Cerpa, Cheril Tapia-Rojas*, Rodrigo A. Quintanilla* Redox Biology, 2018. DOI: https://doi.org/10.1016/j.redox.2018.07.010 Reference: REDOX956.*Corresponding Author.Genetic ablation of tau improves mitochondrial function and cognitive abilities in the hippocampus

Tapia-Rojas C, Inestrosa NC. Neural Regen Res. 2018 Oct;13(10):1705-1710. doi: 10.4103/1673-5374.238606. Review.Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer’s disease

Ramos-Fernández E, Tapia-Rojas C, Ramírez VT, Inestrosa NC. Ramos-Fernández E, Tapia-Rojas C, Ramírez VT, Inestrosa NC. Mol Neurobiol. 2019 Mar;56(3):1870-1882. doi: 10.1007/s12035-018-1162-1. Epub 2018 Jul 2. Factor de Impacto 5.076Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling

Tapia-Rojas C, Cabezas-Opazo F, Deaton CA, Vergara EH, Johnson GVW, Quintanilla RA. Prog Neurobiol. 2019 Apr;175:54-76. doi: 10.1016/j.pneurobio.2018.12.005. Epub 2018 Dec 31. Review.It’s all about tau

Tapia-Rojas C, Torres AK, Quintanilla RA. Neuroscience. 2019 Mar 21;406:356-368. doi: 10.1016/j.neuroscience.2019.03.018. [Epub ahead of print]Adolescence binge alcohol consumption induces hippocampal mitochondrial impairment that persists during the adulthood

Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C. Nat Cell Biol. 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y. Epub 2019 May 20. Erratum in: Nat Cell Biol. 2019 Jun 14;:.Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics

Pardo E, Barake F, Godoy JA, Oyanadel C, Espinoza S, Metz C, Retamal C, Massardo L, Tapia-Rojas C, Inestrosa NC, Soza A, González A. Mol Neurobiol. 2019 Nov;56(11):7774-7788. doi: 10.1007/s12035-019-1621-3. Epub 2019 May 22.GALECTIN-8 Is a Neuroprotective Factor in the Brain that Can Be Neutralized by Human Autoantibodies

Mira RG, Tapia-Rojas C, Pérez MJ, Jara C, Vergara EH, Quintanilla RA, Cerpa W. Drug Alcohol Depend. 2019 Dec 1;205:107628. doi: 10.1016/j.drugalcdep.2019.107628. Epub 2019 Oct 17. Review. PMID: 31683244Alcohol impairs hippocampal function: From NMDA receptor synaptic transmission to mitochondrial function

Mira RG, Lira M, Tapia-Rojas C, Rebolledo DL, Quintanilla RA, Cerpa W. Front Behav Neurosci. 2020 Jan 24;13:288. doi: 10.3389/fnbeh.2019.00288. eCollection 2019. Review.Effect of Alcohol on Hippocampal-Dependent Plasticity and Behavior: Role of Glutamatergic Synaptic Transmission.

Chang LY, Ardiles AO, Tapia-Rojas C, Araya J, Inestrosa NC, Palacios AG, Acosta ML. Front Neurosci. 2020 Mar 18;14:161. doi: 10.3389/fnins.2020.00161. eCollection 2020.Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus.

Torres AK, Tapia-Rojas C, Cerpa W, Quintanilla RA. Neuroscience. 2020 Jul 1;438:70-85. doi: 10.1016/j.neuroscience.2020.05.005. Epub 2020 May 19. PMID: 32416118Stimulation of Melanocortin Receptor-4 (MC4R) Prevents Mitochondrial Damage Induced by Binge Ethanol Protocol in Adolescent Rat Hippocampus.

Inestrosa NC, Tapia-Rojas C, Lindsay CB, Zolezzi JM. Front Cell Dev Biol. 2020 Aug 5;8:734. doi: 10.3389/fcell.2020.00734. eCollection 2020. PMID: 32850846.Wnt Signaling Pathway Dysregulation in the Aging Brain: Lessons From the Octodon degus

Hernández-Cáceres MP, Cereceda K, Hernández S, Li Y, Narro C, Rivera P, Silva P, Ávalos Y, Jara C, Burgos P, Toledo-Valenzuela L, Lagos P, Cifuentes Araneda F, Perez-Leighton C, Bertocchi C, Clegg DJ, Criollo A, Tapia-Rojas C, Burgos PV, Morselli E. Mol Cell Oncol. 2020 Jul 25;7(5):1789418. doi: 10.1080/23723556.2020.1789418. eCollection 2020. PMID: 32944643.Palmitic acid reduces the autophagic flux in hypothalamic neurons by impairing autophagosome-lysosome fusion and endolysosomal dynamics.

Montecinos-Oliva C, Arrázola MS, Jara C, Tapia-Rojas C*, Inestrosa NC*. Pharmaceuticals (Basel). 2020 Feb 2;13(2). pii: E24. doi: 10.3390/ph13020024. *Corresponding authorsHormetic-Like Effects of L-Homocysteine on Synaptic Structure, Function, and Aβ Aggregation.

Olesen MA, Torres AK, Jara C, Murphy MP, Tapia-Rojas C*. Redox Biol. 2020 May 5;34:101558. doi: 10.1016/j.redox.2020.101558. Online ahead of print. PMID: 32447261 Premature synaptic mitochondrial dysfunction in the hippocampus during aging contributes to memory loss.

Jara C., Cerpa W., Tapia-Rojas C* and Quintanilla RA*. Front Neurosci. 2021 Feb 10;14:586710. doi: 10.3389/fnins.2020.586710. eCollection 2020. PMID: 33679286Tau deletion prevents cognitive impairment and mitochondrial dysfunction age-associated by a mechanism dependent on Cyclophilin-D (CypD).

Angie K. Torres, Claudia Jara, Margrethe A. Olesen, Cheril Tapia-Rojas*. 2021, Scientifics Report. Sci Rep. 2021 Feb 24;11(1):4448. doi: 10.1038/s41598-021-83910-w. PMID: 33627790Pathologically phosphorylated tau at S396/404 (PHF-1) is accumulated inside of hippocampal synaptic mitochondria of aged Wild-type mice

Inestrosa NC, Tapia-Rojas C, Cerpa W, Cisternas P, Zolezzi JM. Handb Exp Pharmacol. 2021;269:357-382. doi: 10.1007/164_2021_532. PMID: 34486097WNT Signaling Is a Key Player in Alzheimer’s Disease.

Torres AK, Jara C, Park-Kang HS, Polanco CM, Tapia D, Alarcón F, de la Peña A, Llanquinao J, Vargas-Mardones G, Indo JA, Inestrosa NC, Tapia-Rojas C*. J Alzheimers Dis. 2021;84(4):1391-1414. doi: 10.3233/JAD-215139. PMID: 34719499 Review.Synaptic Mitochondria: An Early Target of Amyloid-β and Tau in Alzheimer’s Disease.

Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer's disease. Torres AK, Rivera BI, Polanco CM, Jara C, Tapia-Rojas C*. Neural Regen Res. 2022 Aug;17(8):1645-1651. doi: 10.4103/1673-5374.332125. PMID: 35017410. Review.

Other publications

  1. Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer’s disease. Torres AK, Rivera BI, Polanco CM, Jara C, Tapia-Rojas C*. Neural Regen Res. 2022 Aug;17(8):1645-1651. doi: 10.4103/1673-5374.332125. PMID: 35017410. Review.
  2. Synaptic Mitochondria: An Early Target of Amyloid-β and Tau in Alzheimer’s Disease. Torres AK, Jara C, Park-Kang HS, Polanco CM, Tapia D, Alarcón F, de la Peña A, Llanquinao J, Vargas-Mardones G, Indo JA, Inestrosa NC, Tapia-Rojas C*. J Alzheimers Dis. 2021;84(4):1391-1414. doi: 10.3233/JAD-215139. PMID: 34719499 Review.
  3. WNT Signaling Is a Key Player in Alzheimer’s Disease. Inestrosa NC, Tapia-Rojas C, Cerpa W, Cisternas P, Zolezzi JM. Handb Exp Pharmacol. 2021;269:357-382. doi: 10.1007/164_2021_532. PMID: 34486097
  4. Pathologically phosphorylated tau at S396/404 (PHF-1) is accumulated inside of hippocampal synaptic mitochondria of aged Wild-type mice. Angie K. Torres, Claudia Jara, Margrethe A. Olesen, Cheril Tapia-Rojas*. 2021, Scientifics Report. Sci Rep. 2021 Feb 24;11(1):4448. doi: 10.1038/s41598-021-83910-w. PMID: 33627790
  5. Tau deletion prevents cognitive impairment and mitochondrial dysfunction age-associated by a mechanism dependent on Cyclophilin-D (CypD). Jara C., Cerpa W., Tapia-Rojas C* and Quintanilla RA*. Front Neurosci. 2021 Feb 10;14:586710. doi: 10.3389/fnins.2020.586710. eCollection 2020. PMID: 33679286
  6. Premature synaptic mitochondrial dysfunction in the hippocampus during aging contributes to memory loss. Olesen MA, Torres AK, Jara C, Murphy MP, Tapia-Rojas C*. Redox Biol. 2020 May 5;34:101558. doi: 10.1016/j.redox.2020.101558. Online ahead of print. PMID: 32447261
  7. Hormetic-Like Effects of L-Homocysteine on Synaptic Structure, Function, and Aβ Aggregation. Montecinos-Oliva C, Arrázola MS, Jara C, Tapia-Rojas C*, Inestrosa NC*. Pharmaceuticals (Basel). 2020 Feb 2;13(2). pii: E24. doi: 10.3390/ph13020024. *Corresponding authors
  8. Palmitic acid reduces the autophagic flux in hypothalamic neurons by impairing autophagosome-lysosome fusion and endolysosomal dynamics. Hernández-Cáceres MP, Cereceda K, Hernández S, Li Y, Narro C, Rivera P, Silva P, Ávalos Y, Jara C, Burgos P, Toledo-Valenzuela L, Lagos P, Cifuentes Araneda F, Perez-Leighton C, Bertocchi C, Clegg DJ, Criollo A, Tapia-Rojas C, Burgos PV, Morselli E. Mol Cell Oncol. 2020 Jul 25;7(5):1789418. doi: 10.1080/23723556.2020.1789418. eCollection 2020. PMID: 32944643.
  9. Wnt Signaling Pathway Dysregulation in the Aging Brain: Lessons From the Octodon degus. Inestrosa NC, Tapia-Rojas C, Lindsay CB, Zolezzi JM. Front Cell Dev Biol. 2020 Aug 5;8:734. doi: 10.3389/fcell.2020.00734. eCollection 2020. PMID: 32850846.
  10. Stimulation of Melanocortin Receptor-4 (MC4R) Prevents Mitochondrial Damage Induced by Binge Ethanol Protocol in Adolescent Rat Hippocampus. Torres AK, Tapia-Rojas C, Cerpa W, Quintanilla RA. Neuroscience. 2020 Jul 1;438:70-85. doi: 10.1016/j.neuroscience.2020.05.005. Epub 2020 May 19. PMID: 32416118
  11. Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus. Chang LY, Ardiles AO, Tapia-Rojas C, Araya J, Inestrosa NC, Palacios AG, Acosta ML. Front Neurosci. 2020 Mar 18;14:161. doi: 10.3389/fnins.2020.00161. eCollection 2020.
  12. Effect of Alcohol on Hippocampal-Dependent Plasticity and Behavior: Role of Glutamatergic Synaptic Transmission. Mira RG, Lira M, Tapia-Rojas C, Rebolledo DL, Quintanilla RA, Cerpa W. Front Behav Neurosci. 2020 Jan 24;13:288. doi: 10.3389/fnbeh.2019.00288. eCollection 2019. Review.
  13. Alcohol impairs hippocampal function: From NMDA receptor synaptic transmission to mitochondrial function. Mira RG, Tapia-Rojas C, Pérez MJ, Jara C, Vergara EH, Quintanilla RA, Cerpa W. Drug Alcohol Depend. 2019 Dec 1;205:107628. doi: 10.1016/j.drugalcdep.2019.107628. Epub 2019 Oct 17. Review. PMID: 31683244
  14. GALECTIN-8 Is a Neuroprotective Factor in the Brain that Can Be Neutralized by Human Autoantibodies. Pardo E, Barake F, Godoy JA, Oyanadel C, Espinoza S, Metz C, Retamal C, Massardo L, Tapia-Rojas C, Inestrosa NC, Soza A, González A. Mol Neurobiol. 2019 Nov;56(11):7774-7788. doi: 10.1007/s12035-019-1621-3. Epub 2019 May 22.
  15. Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics. Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C. Nat Cell Biol. 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y. Epub 2019 May 20. Erratum in: Nat Cell Biol. 2019 Jun 14;:.
  16. Adolescence binge alcohol consumption induces hippocampal mitochondrial impairment that persists during the adulthood. Tapia-Rojas C, Torres AK, Quintanilla RA. Neuroscience. 2019 Mar 21;406:356-368. doi: 10.1016/j.neuroscience.2019.03.018. [Epub ahead of print]
  17. It’s all about tau. Tapia-Rojas C, Cabezas-Opazo F, Deaton CA, Vergara EH, Johnson GVW, Quintanilla RA. Prog Neurobiol. 2019 Apr;175:54-76. doi: 10.1016/j.pneurobio.2018.12.005. Epub 2018 Dec 31. Review.
  18. Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling. Ramos-Fernández E, Tapia-Rojas C, Ramírez VT, Inestrosa NC. Ramos-Fernández E, Tapia-Rojas C, Ramírez VT, Inestrosa NC. Mol Neurobiol. 2019 Mar;56(3):1870-1882. doi: 10.1007/s12035-018-1162-1. Epub 2018 Jul 2. Factor de Impacto 5.076
  19. Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer’s disease. Tapia-Rojas C, Inestrosa NC. Neural Regen Res. 2018 Oct;13(10):1705-1710. doi: 10.4103/1673-5374.238606. Review.
  20. Genetic ablation of tau improves mitochondrial function and cognitive abilities in the hippocampus. Claudia Jara, Alejandra Aránguiz, Waldo Cerpa, Cheril Tapia-Rojas*, Rodrigo A. Quintanilla* Redox Biology, 2018. DOI: https://doi.org/10.1016/j.redox.2018.07.010 Reference: REDOX956.*Corresponding Author.
  21. Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer’s disease in J20-APP transgenic and wild-type mice. Tapia-Rojas C, Inestrosa NC. J Neurochem. 2018 Feb;144(4):443-465. doi: 10.1111/jnc.14278. Epub 2018 Jan 26.
  22. Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment. Tapia-Rojas C, Carvajal FJ, Mira RG, Arce C, Lerma-Cabrera JM, Orellana JA, Cerpa W, Quintanilla RA. Mol Neurobiol. 2018 May;55(5):4473-4491. doi: 10.1007/s12035-017-0613-4. Epub 2017 Jun 1.
  23. Alcohol consumption during adolescence: A link between mitochondrial damage and ethanol brain intoxication. Tapia-Rojas C, Mira RG, Torres AK, Jara C, Pérez MJ, Vergara EH, Cerpa W, Quintanilla RA. Birth Defects Res. 2017 Dec 1;109(20):1623-1639. doi: 10.1002/bdr2.1172. Review.
  24. Possible role of mitochondrial permeability transition pore in the pathogenesis of Huntington disease. QuintanillaRA, Tapia C, Pérez MJ. Biochem Biophys Res Commun. 2017 Feb 19;483(4):1078-1083. doi: 10.1016/j.bbrc.2016.09.054. Epub 2016 Sep 13. Review.
  25. Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid-β (Aβ)42 peptides. Tapia-Rojas C, Burgos PV, Inestrosa NC. J Neurochem. 2016 Dec;139(6):1175-1191. doi: 10.1111/jnc.13873.
  26. Voluntary Running Attenuates Memory Loss, Decreases Neuropathological Changes and Induces Neurogenesis in a Mouse Model of Alzheimer’s Disease. Tapia-Rojas C, Aranguiz F, Varela-Nallar L, Inestrosa NC. Brain Pathol. 2016 Jan;26(1):62-74. doi: 10.1111/bpa.12255. Epub 2015 May 7.
  27. Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice. Tapia-Rojas C, Lindsay CB, Montecinos-Oliva C, Arrazola MS, Retamales RM, Bunout D, Hirsch S, Inestrosa NC. Mol Neurodegener. 2015 Nov 21;10:62. doi: 10.1186/s13024-015-0057-0.
  28. Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3β in vivo. Tapia-Rojas C, Schüller A, Lindsay CB, Ureta RC, Mejías-Reyes C, Hancke J, Melo F, Inestrosa NC. Biochem J. 2015 Mar 1;466(2):415-30. doi: 10.1042/BJ20140207.
  29. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus. Varela-Nallar L, Arredondo SB, Tapia-Rojas C, Hancke J, Inestrosa NC. Neural Plast. 2015;2015:935403. doi: 10.1155/2015/935403. Epub 2015 Dec 22.
  30. Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy. Fuenzalida M, Espinoza C, Pérez MÁ, Tapia-Rojas C, Cuitino L, Brandan E, Inestrosa NC. Neurobiol Dis. 2016 Feb;86:109-20. doi: 10.1016/j.nbd.2015.11.018. Epub 2015 Dec 2.
  31. Rhein-huprine derivatives reduce cognitive impairment, synaptic failure and amyloid pathology in AβPPswe/PS-1 mice of different ages. Serrano FG, Tapia-Rojas C, Carvajal FJ, Cisternas P, Viayna E, Irene S, Muñoz-Torrero D, Inestrosa NC. Curr Alzheimer Res. 2015 Oct 27. [Epub ahead of print]
  32. β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats. Cuevas CA, Tapia-Rojas C, Cespedes C, Inestrosa NC, Vio CP. Biomed Res Int. 2015;2015:726012. doi: 10.1155/2015/726012. Epub 2015 Apr 7.
  33. Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus. Du LY, Chang LY, Ardiles AO, Tapia-Rojas C, Araya J, Inestrosa NC, Palacios AG, Acosta ML. PLoS One. 2015 Aug 12;10(8):e0135499. doi: 10.1371/journal.pone.0135499. eCollection 20
  34. Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy. Cavieres VA, González A, Muñoz VC, Yefi CP, Bustamante HA, Barraza RR, Tapia-Rojas C, Otth C, Barrera MJ, González C, Mardones GA, Inestrosa NC, Burgos PV. PLoS One. 2015 Aug 26;10(8):e0136313. doi: 10.1371/journal.pone.0136313. eCollection 2015.
  35. Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus, a Natural Model of Alzheimer’s Disease. Inestrosa NC, Ríos JA, Cisternas P, Tapia-Rojas C, Rivera DS, Braidy N, Zolezzi JM, Godoy JA, Carvajal FJ, Ardiles AO, Bozinovic F, Palacios AG, Sachdev PS. Brain Pathol. 2015 Nov;25(6):679-91. doi: 10.1111/bpa.12226. Epub 2015 Feb 10.
  36. Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice. Serrano FG, Tapia-Rojas C, Carvajal FJ, Hancke J, Cerpa W, Inestrosa NC. Mol Neurodegener. 2014 Dec 18;9:61. doi: 10.1186/1750-1326-9-61.
  37. Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents. Viayna E, Sola I, Bartolini M, De Simone A, Tapia-Rojas C, Serrano FG, Sabaté R, Juárez-Jiménez J, Pérez B, Luque FJ, Andrisano V, Clos MV, Inestrosa NC, Muñoz-Torrero D. J Med Chem. 2014 Mar 27;57(6):2549-67. doi: 10.1021/jm401824w. Epub 2014 Mar 10.
  38. Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer’s disease. Inestrosa NC, Carvajal FJ, Zolezzi JM, Tapia-Rojas C, Serrano F, Karmelic D, Toledo EM, Toro A, Toro J, Santos MJ. J Alzheimers Dis. 2013;33(4):941-59. doi: 10.3233/JAD-2012-120397.
  39. Tetrahydrohyperforin Decreases Cholinergic Markers associated with Amyloid-β Plaques, 4-Hydroxynonenal Formation, and Caspase-3 Activation in AβPP/PS1 Mice. Carvajal FJ, Zolezzi JM, Tapia-Rojas C, Godoy JA, Inestrosa NC. J Alzheimers Dis. 2013 Jan 1;36(1):99-118. doi: 10.3233/JAD-130230.
  40. Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer’s disease. Ardiles AO, Tapia-Rojas CC, Mandal M, Alexandre F, Kirkwood A, Inestrosa NC, Palacios AG. Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13835-40. doi: 10.1073/pnas.1201209109. Epub 2012 Aug 6.
  41. Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer’s disease: a possible effect on APP processing. Inestrosa NC, Tapia-Rojas C, Griffith TN, Carvajal FJ, Benito MJ, Rivera-Dictter A, Alvarez AR, Serrano FG, Hancke JL, Burgos PV, Parodi J, Varela-Nallar L. Transl Psychiatry. 2011 Jul 12;1:e20. doi: 10.1038/tp.2011.19.

Principal investigator

Cheril Tapia

+56989192971

cheril.tapia@uss.cl

Biography

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