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Article: Editorial: New insights into the role of neuroinflammation and glial cells in the development of neurological disorders.

Pérez-González, Marta / Solas, Maite / Wu, Yixing / Mela, Virginia

2023 Volume 17, Page(s) 1170013

Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1170013
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Article ; Online: Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture.

Muza, Phillip M / Bush, Daniel / Pérez-González, Marta / Zouhair, Ines / Cleverley, Karen / Sopena, Miriam L / Aoidi, Rifdat / West, Steven J / Good, Mark / Tybulewicz, Victor L J / Walker, Matthew C / Fisher, Elizabeth M C / Chang, Pishan

iScience

2023 Volume 26, Issue 2, Page(s) 106073

Abstract: The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated ... ...

Abstract	The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21.
Language	English
Publishing date	2023-01-28
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106073
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Article ; Online: Identifying the Main Functional Pathways Associated with Cognitive Resilience to Alzheimer's Disease.

Pérez-González, Marta / Badesso, Sara / Lorenzo, Elena / Guruceaga, Elizabeth / Pérez-Mediavilla, Alberto / García-Osta, Ana / Cuadrado-Tejedor, Mar

International journal of molecular sciences

2021 Volume 22, Issue 17

Abstract: Understanding the mechanisms involved in cognitive resilience in Alzheimer's disease (AD) represents a promising strategy to identify novel treatments for dementia in AD. Previous findings from our group revealed that the study of aged-Tg2576 cognitive ... ...

Abstract	Understanding the mechanisms involved in cognitive resilience in Alzheimer's disease (AD) represents a promising strategy to identify novel treatments for dementia in AD. Previous findings from our group revealed that the study of aged-Tg2576 cognitive resilient individuals is a suitable tool for this purpose. In the present study, we performed a transcriptomic analysis using the prefrontal cortex of demented and resilient Tg2576 transgenic AD mice. We have been able to hypothesize that pathways involved in inflammation, amyloid degradation, memory function, and neurotransmission may be playing a role on cognitive resilience in AD. Intriguingly, the results obtained in this study are suggestive of a reduction of the influx of peripheral immune cells into the brain on cognitive resilient subjects. Indeed,
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/immunology ; Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Animals ; CD4 Antigens/genetics ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiology ; Cognition ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammation ; Leukocytes, Mononuclear/metabolism ; Male ; Mice ; Mice, Transgenic ; Middle Aged ; Prefrontal Cortex/metabolism ; Temporal Lobe/metabolism
Chemical Substances	CD4 Antigens
Language	English
Publishing date	2021-08-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22179120
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Article ; Online: Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer's Disease.

Cuadrado-Tejedor, Mar / Pérez-González, Marta / Alfaro-Ruiz, Rocío / Badesso, Sara / Sucunza, Diego / Espelosin, María / Ursúa, Susana / Lachen-Montes, Mercedes / Fernández-Irigoyen, Joaquín / Santamaria, Enrique / Luján, Rafael / García-Osta, Ana

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer's disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the ... ...

Abstract	Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer's disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9) carrying the mutant P301L form of human
MeSH term(s)	Alzheimer Disease/complications ; Amyloid beta-Peptides/adverse effects ; Amyloid beta-Protein Precursor/physiology ; Animals ; Cognition Disorders/etiology ; Cognition Disorders/metabolism ; Cognition Disorders/pathology ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondria/metabolism ; Mitochondria/pathology ; Phosphorylation ; Presenilin-1/physiology ; Synapses ; tau Proteins/genetics ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Presenilin-1 ; tau Proteins
Language	English
Publishing date	2021-11-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222111950
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Article ; Online: Irreversible Electroporation in Locally Advanced Pancreatic Adenocarcinoma: Aiming to Improve Overall Survival.

Enjuto, Diego Tristán / Herrera Merino, Norberto / Abadal Villandrade, José María / Gálvez González, Esther / Llorente Lázaro, Rosa / Díaz Peña, Patricia / Álvarez Pérez, María Jesús / Pérez González, Marta

Journal of gastrointestinal cancer

2020 Volume 51, Issue 3, Page(s) 1084–1087

Abstract: Irreversible electroporation (IRE) is a non-thermic ablation therapy which has been proposed for locally advanced pancreatic adenocarcinoma (LAPC) as well as for the local control of other types of tumors (kidney or liver). Its use has been extended in ... ...

Abstract	Irreversible electroporation (IRE) is a non-thermic ablation therapy which has been proposed for locally advanced pancreatic adenocarcinoma (LAPC) as well as for the local control of other types of tumors (kidney or liver). Its use has been extended in the last few years worldwide. Its advantage over other ablation techniques is that it only affects the lipids bilayer of the cell membrane avoiding vascular damage. Safety and viability have been demonstrated in recent studies. Overall survival seems (OS) to improve when it is combined with chemotherapy compared to chemotherapy with or without radiotherapy. Clinical trials should confirm these encouraging data.
MeSH term(s)	Adenocarcinoma/mortality ; Adenocarcinoma/pathology ; Adenocarcinoma/surgery ; Electroporation/methods ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Survival Rate ; Treatment Outcome
Language	English
Publishing date	2020-05-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2452514-5
ISSN	1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
ISSN (online)	1941-6636 ; 1559-0739
ISSN	1941-6628 ; 1537-3649
DOI	10.1007/s12029-020-00425-9
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Article ; Online: PLA2G4E, a candidate gene for resilience in Alzheimer´s disease and a new target for dementia treatment.

Pérez-González, Marta / Mendioroz, Maite / Badesso, Sara / Sucunza, Diego / Roldan, Miren / Espelosín, Maria / Ursua, Susana / Luján, Rafael / Cuadrado-Tejedor, Mar / Garcia-Osta, Ana

Progress in neurobiology

2020 Volume 191, Page(s) 101818

Abstract: Clinical studies revealed that some aged-individuals accumulate a significant number of histopathological Alzheimer´s disease (AD) lesions in their brain, yet without developing any signs of dementia. Animal models of AD represent suitable tools to ... ...

Abstract	Clinical studies revealed that some aged-individuals accumulate a significant number of histopathological Alzheimer´s disease (AD) lesions in their brain, yet without developing any signs of dementia. Animal models of AD represent suitable tools to identify genes that might promote cognitive resilience and hence, this study first set out to identify cognitively resilient individuals in the aged-Tg2576 mouse model. A transcriptomic analysis of these mice identified PLA2G4E as a gene that might confer resistance to dementia. Indeed, a significant decrease in PLA2G4E is evident in the brain of late-stage AD patients, whereas no such changes are observed in early stage patients with AD neuropathological lesions but no signs of dementia. We demonstrated that adeno-associated viral vector-mediated overexpression of PLA2G4E in hippocampal neurons completely restored cognitive deficits in elderly APP/PS1 mice, without affecting the amyloid or tau pathology. These PLA2G4E overexpressing APP/PS1 mice developed significantly more dendritic spines than sham-injected mice, coinciding with the cognitive improvement observed. Hence, these results support the idea that a loss of PLA2G4E might play a key role in the onset of dementia in AD, highlighting the potential of PLA2G4E overexpression as a novel therapeutic strategy to manage AD and other disorders that course with memory deficits.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/therapy ; Animals ; Behavior, Animal/physiology ; Dendritic Spines ; Disease Models, Animal ; Female ; Gene Expression Regulation/genetics ; Genetic Therapy ; Group IV Phospholipases A2/physiology ; Group IV Phospholipases A2/therapeutic use ; Hippocampus ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Spatial Memory
Chemical Substances	Group IV Phospholipases A2 (EC 3.1.1.4) ; PLA2G4E protein, human (EC 3.1.1.4)
Language	English
Publishing date	2020-05-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185535-9
ISSN	1873-5118 ; 0301-0082
ISSN (online)	1873-5118
ISSN	0301-0082
DOI	10.1016/j.pneurobio.2020.101818
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Article ; Online: Autoinmune pancreatitis: Differential diagnosis with pancreatic adenocarcinoma.

Enjuto Martínez, Diego Tristán / Herrera Merino, Norberto / Pérez González, Marta / Llorente Lázaro, Rosa / Castro Carbajo, Pilar

Cirugia espanola

2017 Volume 95, Issue 8, Page(s) 480–482

Title translation	Pancreatitis autoinmune: diagnóstico diferencial con adenocarcinoma de páncreas.
MeSH term(s)	Adenocarcinoma/diagnosis ; Autoimmune Diseases/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/diagnosis ; Pancreatitis/diagnosis
Language	Spanish
Publishing date	2017-01-14
Publishing country	Spain
Document type	Case Reports ; Letter
ZDB-ID	730701-9
ISSN	1578-147X ; 0009-739X
ISSN (online)	1578-147X
ISSN	0009-739X
DOI	10.1016/j.ciresp.2016.11.005
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Article: Taking Advantage of the Selectivity of Histone Deacetylases and Phosphodiesterase Inhibitors to Design Better Therapeutic Strategies to Treat Alzheimer's Disease.

Cuadrado-Tejedor, Mar / Pérez-González, Marta / García-Muñoz, Cristina / Muruzabal, Damián / García-Barroso, Carolina / Rabal, Obdulia / Segura, Víctor / Sánchez-Arias, Juan A / Oyarzabal, Julen / Garcia-Osta, Ana

Frontiers in aging neuroscience

2019 Volume 11, Page(s) 149

Abstract: The discouraging results with therapies for Alzheimer's disease (AD) in clinical trials, highlights the urgent need to adopt new approaches. Like other complex diseases, it is becoming clear that AD therapies should focus on the simultaneous modulation ... ...

Abstract	The discouraging results with therapies for Alzheimer's disease (AD) in clinical trials, highlights the urgent need to adopt new approaches. Like other complex diseases, it is becoming clear that AD therapies should focus on the simultaneous modulation of several targets implicated in the disease. Recently, using reference compounds and the first-in class CM-414, we demonstrated that the simultaneous inhibition of histone deacetylases [class I histone deacetylases (HDACs) and HDAC6] and phosphodiesterase 5 (PDE5) has a synergistic therapeutic effect in AD models. To identify the best inhibitory balance of HDAC isoforms and PDEs that provides a safe and efficient therapy to combat AD, we tested the compound CM-695 in the Tg2576 mouse model of this disease. CM-695 selectively inhibits HDAC6 over class I HDAC isoforms, which largely overcomes the toxicity associated with HDAC class 1 inhibition. Furthermore, CM-695 inhibits PDE9, which is expressed strongly in the brain and has been proposed as a therapeutic target for AD. Chronic treatment of aged Tg2576 mice with CM-695 ameliorates memory impairment and diminishes brain Aβ, although its therapeutic effect was no longer apparent 4 weeks after the treatment was interrupted. An increase in the presence of 78-KDa glucose regulated protein (GRP78) and heat shock protein 70 (Hsp70) chaperones may underlie the therapeutic effect of CM-695. In summary, chronic treatment with CM-695 appears to reverse the AD phenotype in a safe and effective manner. Taking into account that AD is a multifactorial disorder, the multimodal action of these compounds and the different events they affect may open new avenues to combat AD.
Language	English
Publishing date	2019-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2019.00149
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Article: Lower gastrointestinal bleeding as a presentation of miliary tuberculosis.

Abelenda Alonso, Gabriela / Fernández-Marcote, Eva Marina / Martín-Crespo Posada, David / Pérez González, Marta / Martínez Albares, Jose Luis

Gastroenterologia y hepatologia

2016 Volume 39, Issue 8, Page(s) 527–529

Language	English
Publishing date	2016-10
Publishing country	Spain
Document type	Journal Article
ZDB-ID	632502-6
ISSN	0210-5705
ISSN	0210-5705
DOI	10.1016/j.gastrohep.2015.08.004
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Article: Immunomodulatory Properties of Carvone Inhalation and Its Effects on Contextual Fear Memory in Mice.

Lasarte-Cia, Aritz / Lozano, Teresa / Pérez-González, Marta / Gorraiz, Marta / Iribarren, Kristina / Hervás-Stubbs, Sandra / Sarobe, Pablo / Rabal, Obdulia / Cuadrado-Tejedor, Mar / García-Osta, Ana / Casares, Noelia / Lasarte, Juan José

Frontiers in immunology

2018 Volume 9, Page(s) 68

Abstract: A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and ... ...

Abstract	A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and cognitive activity. We performed an exploratory study of the immunomodulatory ability of a series of compounds representing each of the 10 odor categories or clusters described previously. We evaluated the impact of each particular odor on the immune response after immunization with the model antigen ovalbumin in combination with the TLR3 agonist poly I:C. We found that some odors behave as immunostimulatory agents, whereas others might be considered as potential immunosuppressant odors. Interestingly, the immunomodulatory capacity was, in some cases, strain-specific. In particular, one of the fragrances, carvone, was found to be immunostimulatory in BALB/c mice and immunosuppressive in C57BL/6J mice, facilitating or impairing viral clearance, respectively, in a model of a viral infection with a recombinant adenovirus. Importantly, inhalation of the odor improved the memory capacity in BALB/c mice in a fear-conditioning test, while it impaired this same capacity in C57BL/6J mice. The improvement in memory capacity in BALB/c was associated with higher CD3
MeSH term(s)	Administration, Inhalation ; Animals ; Cognition ; Conditioning (Psychology) ; Disease Models, Animal ; Disease Susceptibility ; Fear/psychology ; Female ; Gene Expression Profiling ; Hippocampus/drug effects ; Hippocampus/metabolism ; Hippocampus/pathology ; Immunologic Factors/administration & dosage ; Immunologic Factors/pharmacology ; Immunomodulation/drug effects ; Immunomodulation/genetics ; Leukocytes/drug effects ; Leukocytes/pathology ; Memory/drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Monoterpenes/administration & dosage ; Monoterpenes/pharmacology ; Odorants ; Virus Diseases/etiology
Chemical Substances	Immunologic Factors ; Monoterpenes ; carvone (75GK9XIA8I)
Language	English
Publishing date	2018-01-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00068
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