Brain development and response to injury : focus on microglia and cranial irradiation DOI
Alejandro Lastra Romero

Published: Sept. 3, 2024

<p dir="ltr">Postnatal brain development is crucial for proper formation and function in adulthood. Impairment of this process due to external insults such as cranial radiotherapy, used treat tumors metastases, can lead severe cognitive sequelae cancer survivors, particularly children. However, currently, neither a treatment nor established biomarkers exist alleviate or predict the extent injury subsequent impairments following radiotherapy.</p><p dir="ltr">Microglia, resident immune cells macrophages brain, play vital role refinement, maturation, maintenance neuronal circuits during development. Therefore, understanding microglial dysregulation caused by ionizing radiation (IR) its impact on neurocognitive outcomes great importance.</p><p dir="ltr">Consequently, primary objective thesis was analyze microglia their response irradiation. This includes specific focus temporary subtypes contribution irradiation-associated neuroinflammation. Additionally, we aimed identify potential irradiation-induced damage that be measured easily accessible clinical samples.</p><p dir="ltr">First, identified spatiotemporally distinct subtype, arginase 1- expressing (ARG1+) microglia. while morphologically similar other cells, exhibits unique molecular profile maturation basal forebrain cholinergic system, synaptic plasticity, functions female mice.</p><p dir="ltr">Next, developed simple, rapid, reproducible cell isolation method generate single-cell suspensions from subregions, enriched with vascular cells. suitable integrative longitudinal studies using RNA sequencing.</p><p dir="ltr">Using method, performed analysis responses IR several hippocampal radiation-associated (RAM) emerge hours one year after IR. We found causes progressive decrease fail repopulate loss self-renewal, leads infiltration monocytes-derived differentiate into microglial-like compensate loss. Moreover, all these events were correlated episodes asynchrony.</p><p dir="ltr">Finally, propose EDA2R promising biomarker candidate IR- induced injury, levels rapidly increase liquid biopsies (cerebrospinal fluid plasma) IR.</p><p dir="ltr">The results presented provide new insights postnatal They also highlight radiotherapy-induced damage.</p><p dir="ltr">In summary, research important field neuroscience. It significant advancing our radiotherapy-related complications, aim improving quality life pediatric survivors.</p><h3>List scientific papers</h3><p dir="ltr">I. Vassilis Stratoulias, Rocío Ruiz, Shigeaki Kanatani, Ahmed M. Osman, Lily Keane, Jose A. Armengol, Antonio Rodríguez-Moreno, Adriana- Natalia Murgoci, Irene García-Domínguez, Isabel Alonso-Bellido, Fernando González Ibáñez, Katherine Picard, Guillermo Vázquez- Cabrera, Mercedes Posada-Pérez, Nathalie Vernoux, Dario Tejera, Kathleen Grabert, Mathilde Cheray, Patricia González-Rodríguez, Eva Pérez-Villegas, Martínez-Gallego, <b>Alejandro Lastra- Romero</b>, David Brodin, Javier Avila-Cariño, Yang Cao, Mikko Airavaara, Per Uhlen, Michael T. Heneka, Marie-Ève Tremblay, Klas Blomgren, L. Venero & Bertrand Joseph. ARG1-expressing show signature modulate mouse brain. Nature Neuroscience, volume 26, pages 1008-1020 (2023).<br><a href="https://doi.org/10.1038/s41593-023-01326-3" rel="noreferrer" target="_blank">https://doi.org/10.1038/s41593-023-01326-3</a></p><p dir="ltr"><br></p><p dir="ltr">II. Efthalia Preka*, Lastra Romero</b>*, Ying Sun, Yara Onetti Vilalta, Thea Seitz, Adamantia Fragkopoulou, Christer Betsholtz, M Blomgren. Rapid robust subregions analyses. Heliyon. 10, issue 16 (2024); e35838. * Denotes equal first-author contribution<br><a href="https://doi.org/10.1016/j.heliyon.2024.e35838" target="_blank">https://doi.org/10.1016/j.heliyon.2024.e35838</a></p><p dir="ltr">III. Giusy Pizzirusso, Luis Enrique Arroyo- Garcia, Georgios Alkis Zisiadis, Nuria Oliva-Vilarnau, Kai Zhou, Arturo Gonzalez Isla, Lara Friess, Alia Shamik, Changlian Zhu, Carlos F. D. Rodrigues, André Fisahn, Joseph, Lena-Maria Carlson, Volker Lauschke, Microglia Adopt Temporally Specific Subtypes Irradiation, Correlating Neuronal Asynchrony. contribution. [Manuscript]</p><p dir="ltr">IV. Holli Jeffery, Osman. reflects acute irradiation biopsies. Neuro-Oncology noae077.<br><a href="https://doi.org/10.1093/neuonc/noae077" target="_blank">https://doi.org/10.1093/neuonc/noae077</a></p>

Language: Английский

Depolymerized peanut skin-derived proanthocyanidins alleviate cognitive dysfunction by inhibiting Aβ42 aggregation in Alzheimer’s disease DOI
He Liu, Ziyan Zhang, Xiaoqing Li

et al.

Food Research International, Journal Year: 2025, Volume and Issue: unknown, P. 115747 - 115747

Published: Jan. 1, 2025

Language: Английский

Citations

1
Neuroprotective Effect of Curcumin–Metavanadate in the Hippocampus of Aged Rats DOI Open Access

Sonia Irais González‐Cano,

Ulises Peña‐Rosas,

Guadalupe Muñoz‐Arenas

et al.

Synapse, Journal Year: 2025, Volume and Issue: 79(1)

Published: Jan. 1, 2025

ABSTRACT Brain aging is a multifactorial process that includes reduction in the biological and metabolic activity of individuals. Oxidative stress inflammatory processes are characteristic brain aging. Given current problems, need arises to implement new therapeutic approaches. Polyoxidovanadates (POV), as well curcumin, have stood out for their participation variety activities. This work aimed evaluate coupling metavanadate curcumin (Cuma‐MV) on learning, memory, redox balance, neuroinflammation, cell death hippocampal region (CA1 CA3) dentate gyrus (DG) aged rats. Rats 18 months old were administered daily dose (Cuma), sodium (MV), or Cuma‐MV two months. The results demonstrated administration 60 days rats improved short‐ long‐term recognition decreased reactive oxygen species, substantially lipoperoxidation hippocampus. Furthermore, superoxide dismutase catalase increased animals treated with Cuma‐MV. It important highlight treatment exhibited significantly greater effect than treatments MV Cuma all parameters evaluated. Finally, we conclude represents potential option prevention cognitive decline associated

Language: Английский

Citations

0
Efficient, Automatic, and Reproducible Patch Clamp Data Analysis with “Auto ANT”, a User-Friendly Interface for Batch Analysis of Patch Clamp Recordings DOI Creative Commons
Giusy Pizzirusso,

Simon Sundström,

Luis Enrique Arroyo‐García

et al.

Neuroinformatics, Journal Year: 2025, Volume and Issue: 23(2)

Published: March 18, 2025

Abstract Patch-clamp recordings are vital for investigating the electrical properties of excitable cells, yet analysis these often involves time-consuming manual procedures prone to variability. To address this challenge, we developed Auto ANT (Automated Analysis and Tables) open-source software, an automated, user-friendly graphical interface extraction firing passive membrane from patch-clamp recordings. Thanks novel built-in automation feature, enables batch multiple files recorded with same protocol in minutes. Our tool is designed streamline data analysis, providing a fast, efficient, reproducible alternative methods. With focus on accessibility, allows users perform precise comprehensive electrophysiological analyses without requiring programming expertise. By combining user-centric design, offers valuable resource researchers accelerate while promoting consistency reproducibility across different studies.

Language: Английский

Citations

0
Therapeutic Targets in Innate Immunity to Tackle Alzheimer’s Disease DOI Creative Commons

Maria L. Serradas,

Yingying Ding,

Paula Martorell

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1426 - 1426

Published: Aug. 26, 2024

There is an urgent need for effective disease-modifying therapeutic interventions Alzheimer's disease (AD)-the most prevalent cause of dementia with a profound socioeconomic burden. Most clinical trials targeting the classical hallmarks this disease-β-amyloid plaques and neurofibrillary tangles-failed, showed discrete effects, or were accompanied by concerning side effects. has been ongoing search novel targets. Neuroinflammation, now widely recognized as hallmark all neurodegenerative diseases, proven to be major contributor AD pathology. Here, we summarize role neuroinflammation in pathogenesis progression discuss potential targets such microglia, TREM2, complement system, inflammasomes, cytosolic DNA sensors. We also present overview studies specific innate immune system components, highlighting progress field drug research while bringing attention delicate nature modulations AD.

Language: Английский

Citations

2
Pleiotrophin modulates acute and long-term LPS-induced neuroinflammatory responses and hippocampal neurogenesis DOI Creative Commons

María Rodríguez‐Zapata,

Rosario López‐Rodríguez, Pilar Ramos

et al.

Toxicology, Journal Year: 2024, Volume and Issue: 509, P. 153947 - 153947

Published: Sept. 8, 2024

Language: Английский

Citations

2
An integration-free induced pluripotent stem cell line from a 42-year-old female donor with the APOE-ε2/ε2 allele DOI Creative Commons
Lianying Wang,

Ruiyun Guo,

Xiaohan Zhang

et al.

Stem Cell Research, Journal Year: 2024, Volume and Issue: 80, P. 103506 - 103506

Published: July 28, 2024

The APOE 4 allele remains the primary genetic risk factor for sporadic Alzheimer's disease, whereas 2 emerges as a protective factor. Therapeutic approaches in murine models with human alleles, such modulating levels and converting isoforms, show efficacy. However, there is lack of vitro APOE2-mutant neuronal models. Hence, this study, we generated induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear (PMBC) 42-year-old female donor carrying APOE-ε2/ε2 allele. newly hiPSC displayed normal karyotype could differentiate into three germ layers. Besides, they retained their original genotype expressed pluripotency markers.

Language: Английский

Citations

0
Brain development and response to injury : focus on microglia and cranial irradiation DOI
Alejandro Lastra Romero

Published: Sept. 3, 2024

<p dir="ltr">Postnatal brain development is crucial for proper formation and function in adulthood. Impairment of this process due to external insults such as cranial radiotherapy, used treat tumors metastases, can lead severe cognitive sequelae cancer survivors, particularly children. However, currently, neither a treatment nor established biomarkers exist alleviate or predict the extent injury subsequent impairments following radiotherapy.</p><p dir="ltr">Microglia, resident immune cells macrophages brain, play vital role refinement, maturation, maintenance neuronal circuits during development. Therefore, understanding microglial dysregulation caused by ionizing radiation (IR) its impact on neurocognitive outcomes great importance.</p><p dir="ltr">Consequently, primary objective thesis was analyze microglia their response irradiation. This includes specific focus temporary subtypes contribution irradiation-associated neuroinflammation. Additionally, we aimed identify potential irradiation-induced damage that be measured easily accessible clinical samples.</p><p dir="ltr">First, identified spatiotemporally distinct subtype, arginase 1- expressing (ARG1+) microglia. while morphologically similar other cells, exhibits unique molecular profile maturation basal forebrain cholinergic system, synaptic plasticity, functions female mice.</p><p dir="ltr">Next, developed simple, rapid, reproducible cell isolation method generate single-cell suspensions from subregions, enriched with vascular cells. suitable integrative longitudinal studies using RNA sequencing.</p><p dir="ltr">Using method, performed analysis responses IR several hippocampal radiation-associated (RAM) emerge hours one year after IR. We found causes progressive decrease fail repopulate loss self-renewal, leads infiltration monocytes-derived differentiate into microglial-like compensate loss. Moreover, all these events were correlated episodes asynchrony.</p><p dir="ltr">Finally, propose EDA2R promising biomarker candidate IR- induced injury, levels rapidly increase liquid biopsies (cerebrospinal fluid plasma) IR.</p><p dir="ltr">The results presented provide new insights postnatal They also highlight radiotherapy-induced damage.</p><p dir="ltr">In summary, research important field neuroscience. It significant advancing our radiotherapy-related complications, aim improving quality life pediatric survivors.</p><h3>List scientific papers</h3><p dir="ltr">I. Vassilis Stratoulias, Rocío Ruiz, Shigeaki Kanatani, Ahmed M. Osman, Lily Keane, Jose A. Armengol, Antonio Rodríguez-Moreno, Adriana- Natalia Murgoci, Irene García-Domínguez, Isabel Alonso-Bellido, Fernando González Ibáñez, Katherine Picard, Guillermo Vázquez- Cabrera, Mercedes Posada-Pérez, Nathalie Vernoux, Dario Tejera, Kathleen Grabert, Mathilde Cheray, Patricia González-Rodríguez, Eva Pérez-Villegas, Martínez-Gallego, <b>Alejandro Lastra- Romero</b>, David Brodin, Javier Avila-Cariño, Yang Cao, Mikko Airavaara, Per Uhlen, Michael T. Heneka, Marie-Ève Tremblay, Klas Blomgren, L. Venero & Bertrand Joseph. ARG1-expressing show signature modulate mouse brain. Nature Neuroscience, volume 26, pages 1008-1020 (2023).<br><a href="https://doi.org/10.1038/s41593-023-01326-3" rel="noreferrer" target="_blank">https://doi.org/10.1038/s41593-023-01326-3</a></p><p dir="ltr"><br></p><p dir="ltr">II. Efthalia Preka*, Lastra Romero</b>*, Ying Sun, Yara Onetti Vilalta, Thea Seitz, Adamantia Fragkopoulou, Christer Betsholtz, M Blomgren. Rapid robust subregions analyses. Heliyon. 10, issue 16 (2024); e35838. * Denotes equal first-author contribution<br><a href="https://doi.org/10.1016/j.heliyon.2024.e35838" target="_blank">https://doi.org/10.1016/j.heliyon.2024.e35838</a></p><p dir="ltr">III. Giusy Pizzirusso, Luis Enrique Arroyo- Garcia, Georgios Alkis Zisiadis, Nuria Oliva-Vilarnau, Kai Zhou, Arturo Gonzalez Isla, Lara Friess, Alia Shamik, Changlian Zhu, Carlos F. D. Rodrigues, André Fisahn, Joseph, Lena-Maria Carlson, Volker Lauschke, Microglia Adopt Temporally Specific Subtypes Irradiation, Correlating Neuronal Asynchrony. contribution. [Manuscript]</p><p dir="ltr">IV. Holli Jeffery, Osman. reflects acute irradiation biopsies. Neuro-Oncology noae077.<br><a href="https://doi.org/10.1093/neuonc/noae077" target="_blank">https://doi.org/10.1093/neuonc/noae077</a></p>

Language: Английский

Citations

0