Review
Neurosciences
Gaifen Li, Jia Liu, Yuying Guan, Xunming Ji
Summary: Hypoxia plays a crucial role in regulating various cell functions, including stem cells and neural stem cells. Hypoxia stimulation in specific brain regions can promote proliferation, migration, and maturation of neural stem cells, potentially offering a promising strategy for treating central nervous system diseases.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Review
Cell Biology
Luka Culig, Xixia Chu, Vilhelm A. Bohr
Summary: Adult neurogenesis is a potential target for extending cognitive healthspan, as aging is a major risk factor for neurodegenerative diseases. This review describes the role of adult neurogenesis in neurodegenerative diseases and discusses the molecular mechanisms involving key proteins. Interventions that increase neurogenesis and regulate aging research targets are summarized, and the outlook for restoring neurogenesis levels in elderly individuals and those with neurodegeneration is shared.
AGEING RESEARCH REVIEWS
(2022)
Article
Cell Biology
Laura Micheli, Giorgio D'Andrea, Teresa Maria Creanza, Daniel Volpe, Nicola Ancona, Raffaella Scardigli, Felice Tirone
Summary: Neural stem cells in neurogenic niches divide throughout adulthood, but their number decreases with age. The cyclin-dependent kinase inhibitor p16Ink4a plays a role in maintaining the pool of stem cells in aged mice. It regulates stem cell self-renewal and prevents their activation after a neurogenic stimulus. Transcriptome analysis of the dentate gyrus in p16Ink4a knockout mice revealed genes involved in apoptotic, neuroinflammation, synaptic activity, and stem cell activation processes. These findings contribute to understanding the regulation of stem cell reactivity and provide insights into potential therapeutic targets for age-related neurodegenerative diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Neurosciences
Aikaterini Lampada, Verdon Taylor
Summary: Neurogenesis stops in most areas of the mammalian brain before or shortly after birth, but in certain brain regions, the production of new neurons continues into adulthood. Neural stem cells in these neurogenic zones are situated within niches that govern their activity and fate. Majority of adult brain stem cells are mitotically inactive and can remain dormant for extended periods. The molecular mechanisms regulating neural stem cell maintenance and differentiation are of great interest, with Notch signaling identified as a critical regulator in various tissues, including the nervous system. This review examines the roles of Notch signaling, as well as the functions of different Notch receptors and ligands, in the regulation of adult neurogenesis in mice.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Shawn F. Sorrells, Mercedes F. Paredes, Zhuangzhi Zhang, Gugene Kang, Oier Pastor-Alonso, Sean Biagiotti, Chloe E. Page, Kadellyn Sandoval, Anthony Knox, Andrew Connolly, Eric J. Huang, Jose Manuel Garcia-Verdugo, Michael C. Oldham, Zhengang Yang, Arturo Alvarez-Buylla
Summary: Adult hippocampal neurogenesis was initially discovered in rodents, with subsequent studies identifying adult neural stem cells and their links to plasticity, behavior, and disease. The debate continues as to whether new neurons are produced in the human dentate gyrus during healthy aging. Recent research has shown conflicting results regarding the presence of dividing neuronal precursors in the adult human brain.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Joshua D. Rieskamp, Patricia Sarchet, Bryon M. Smith, Elizabeth D. Kirby
Summary: The study estimated the cell density of neural stem/progenitor cells in the dentate gyrus of adult mice using immunohistochemical methods and found that they had similar density as other cell types with secretory functions. These findings contribute to refining hypotheses about the roles of these cell types in regulating hippocampal function and their potential therapeutic uses.
NEURAL REGENERATION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Brenna Hourigan, Spencer D. Balay, Graydon Yee, Saloni Sharma, Qiumin Tan
Summary: New neurons continuously arise in the adult hippocampus, but little is known about the factors regulating neuronal differentiation, migration, and dendrite maturation. Our study reveals a previously unrecognized role of the transcriptional repressor protein CIC in adult hippocampal neurogenesis, as its loss impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons.
SCIENTIFIC REPORTS
(2021)
Review
Cell & Tissue Engineering
Sebastian B. Arredondo, Daniela Valenzuela-Bezanilla, Sebastian H. Santibanez, Lorena Varela-Nallar
Summary: The subgranular zone of the hippocampal dentate gyrus is a neurogenic niche that contains neural stem cells capable of generating granule neurons. Wnt ligands play diverse roles in regulating adult hippocampal neurogenesis. Understanding the cellular source and mechanisms of Wnt signaling will be crucial for future therapeutic interventions.
Review
Biochemistry & Molecular Biology
Gabriel Berdugo-Vega, Shonali Dhingra, Federico Calegari
Summary: This article reviews a wealth of research in cellular, anatomical, behavioral, and computational studies on the mammalian hippocampus, aiming to understand the fundamental mechanisms underlying cognition. Despite accumulating knowledge on how the hippocampus processes and stores information for learning and memory, our understanding of hippocampal cognitive function remains incomplete. The article discusses the structural separability of the two blades of the dentate gyrus in the hippocampus and proposes a model that suggests differences in connectivity and adult neurogenesis in the two blades may contribute to subtly different cognitive functions.
Article
Cell Biology
Laura Micheli, Teresa Maria Creanza, Manuela Ceccarelli, Giorgio D'Andrea, Giacomo Giacovazzo, Nicola Ancona, Roberto Coccurello, Raffaella Scardigli, Felice Tirone
Summary: The deletion of Btg1 gene results in abnormal neurogenesis, but this can be reversed by physical exercise. Through RNA sequencing, we identified genes whose expression is affected in Btg1 knockout mice, and these genes can be counter-regulated by running.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Nannan Guo, Kelsey D. McDermott, Yu-Tzu Shih, Haley Zanga, Debolina Ghosh, Charlotte Herber, William R. Meara, James Coleman, Alexia Zagouras, Lai Ping Wong, Ruslan Sadreyev, J. Tiago Goncalves, Amar Sahay
Summary: This study reveals that the transcription factor Klf9 functions as a brake on symmetric self-renewal of radial-glial neural stem cells (RGLs) in mice. The loss of Klf9 promotes the activation state of RGLs and leads to increased symmetric self-renewal. The study also provides molecular insights into the genetic programs underlying RGL symmetric self-renewal, including Notch and mitogen signaling, cell cycle, fatty acid oxidation, and lipogenesis.
Article
Neurosciences
Matina Tsampoula, Isaak Tarampoulous, Ivi Antoniadou, Yassemi Koutmani, Dimitrios Gkikas, Kostas Vekrellis, Panagiotis K. Politis
Summary: NR5A2 is differentially expressed in the dentate gyrus of the adult hippocampus, with higher levels in neurons compared to adult neural stem/progenitor cells. Overexpression of NR5A2 induces the expression of Prox1 and promotes neuronal differentiation and axon outgrowth. Depletion of NR5A2 results in reduced number of neurons, highlighting its regulatory role in adult hippocampal neurogenesis.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Geriatrics & Gerontology
Heather Bondi, Valeria Bortolotto, Pier Luigi Canonico, Mariagrazia Grilli
Summary: This study found that astrocytes in the hippocampus and entorhinal cortex of middle-aged mice have different responses to aging. Astrocytes in the dorsal DG showed a significant increase in morphological complexity, while astrocytes in the ventral DG and entorhinal cortex underwent remarkable changes. These findings suggest a new level of complexity in structural changes associated with brain aging.
NEUROBIOLOGY OF AGING
(2021)
Review
Neurosciences
Chuanqi Liu, Jiayin Liu, Hong Gong, Tianyao Liu, Xin Li, Xiaotang Fan
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by atypical social communication and repetitive sensory-motor behaviors. Emerging evidence suggests that deficits in hippocampal neurogenesis may play a significant role in the abnormal behaviors observed in ASD. This review summarizes pre-clinical and clinical studies supporting the importance of hippocampal neurogenesis in the pathogenesis of ASD, discusses the potential of enhancing hippocampal neurogenesis as a new therapeutic strategy for ASD, and highlights the prospects of pro-neurogenic therapies for ASD.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Neurosciences
Marta Gronksa-Peski, J. Tiago Goncalves, Jean M. Hebert
Summary: Research shows that an enriched environment promotes adult neurogenesis by increasing the function of fibroblast growth factor receptor (FGFR) within neurogenic cells. Activation of FGFR by an enriched environment signals through FGFR substrate (FRS) to induce stem cell proliferation and via FRS and phospholipase C gamma to increase the number of adult-born neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Irune Diaz-Aparicio, Inaki Paris, Virginia Sierra-Torre, Ainhoa Plaza-Zabala, Noelia Rodriguez-Iglesias, Mar Marquez-Ropero, Sol Beccari, Paloma Huguet, Oihane Abiega, Elena Alberdi, Carlos Matute, Irantzu Bernales, Angela Schulz, Lilla Otrokocsi, Beata Sperlagh, Kaisa E. Happonen, Greg Lemke, Mirjana Maletic-Savatic, Jorge Valero, Amanda Sierra
JOURNAL OF NEUROSCIENCE
(2020)
Article
Cell Biology
Ignacio Jure, Alejandro F. De Nicola, Juan Manuel Encinas, Florencia Labombarda
Summary: The hippocampus undergoes changes after spinal cord injury (SCI), including reduced neurogenesis, reactive astrocytes, increased microglial cells, and the release of pro-inflammatory cytokines in the chronic phase. These alterations may contribute to cognitive deficits observed in rodents and humans.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Roberto Valcarcel-Martin, Soraya Martin-Suarez, Teresa Muro-Garcia, Oier Pastor-Alonso, Fernando Rodriguez de Fonseca, Guillermo Estivil-Torrus, Juan Manuel Encinas
FRONTIERS IN NEUROSCIENCE
(2020)
Article
Clinical Neurology
Virginia Sierra-Torre, Ainhoa Plaza-Zabala, Paolo Bonifazi, Oihane Abiega, Irune Diaz-Aparicio, Saara Tegelberg, Anna-Elina Lehesjoki, Jorge Valero, Amanda Sierra
Article
Multidisciplinary Sciences
C. Madore, Q. Leyrolle, L. Morel, M. Rossitto, A. D. Greenhalgh, J. C. Delpech, M. Martinat, C. Bosch-Bouju, J. Bourel, B. Rani, C. Lacabanne, A. Thomazeau, K. E. Hopperton, S. Beccari, A. Sere, A. Aubert, V De Smedt-Peyrusse, C. Lecours, K. Bisht, L. Fourgeaud, S. Gregoire, L. Bretillon, N. Acar, N. J. Grant, J. Badaut, P. Gressens, A. Sierra, O. Butovsky, M. E. Tremblay, R. P. Bazinet, C. Joffre, A. Nadjar, S. Laye
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Louis N. Manganas, Irene Dura, Sivan Osenberg, Faith Semerci, Mehmet Tosun, Rachana Mishra, Luke Parkitny, Juan M. Encinas, Mirjana Maletic-Savatic
Summary: This study identified the epitope for the NSC-6 antibody as the signaling protein BASP1, which plays a key role in neurite outgrowth and plasticity. Western blot analysis revealed multiple BASP1 isoforms with varying expression levels, correlating with distinct developmental stages in mouse and human brains. The NSC-6 antibody could be a useful marker for neural stem cells in various developmental stages.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Valentina Satta, Cristina Alonso, Paula Diez, Soraya Martin-Suarez, Marta Rubio, Juan M. Encinas, Javier Fernandez-Ruiz, Onintza Sagredo
Summary: The study validated a new mouse model of Dravet syndrome that exhibited seizuring susceptibility and several comorbidities similar to patients, and identified contributions of the endocannabinoid system, inflammatory events, and impaired neurogenesis in the pathology of the disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Editorial Material
Cell & Tissue Engineering
Soraya Martin-Suarez, Juan Manuel Encinas
Summary: The articles highlight the presence of subpopulations of NSCs in the hippocampus, with dynamics of activation and self-renewal that change over time. These subpopulations may be key to preserving NSCs despite the decline in neurogenesis with age.
Correction
Multidisciplinary Sciences
Louis N. Manganas, Irene Dura, Sivan Osenberg, Fatih Semerci, Mehmet Tosun, Rachana Mishra, Luke Parkitny, Juan M. Encinas, Mirjana Maletic-Savatic
SCIENTIFIC REPORTS
(2021)
Editorial Material
Neurosciences
Angelica Zepeda, Juan Manuel Encinas-Perez, Noelia Urban
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Noelia Rodriguez-Iglesias, Agnes Nadjar, Amanda Sierra, Jorge Valero
Summary: The dietary balance of n-6/n-3 PUFAs can affect adult hippocampal neurogenesis and glia in a sex-dependent manner. In mice, a deficiency in n-3 PUFAs exacerbates the reduction in neuroblast number caused by the bacterial endotoxin lipopolysaccharide.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Anabel R. Simoes, Marta Neto, Carolina S. Alves, Mariana B. Santos, Ismael Fernandez-Hernandez, Henrique Veiga-Fernandes, David Brea, Irene Dura, Juan M. Encinas, Christa Rhiner
Summary: Recruitment of stem cells is crucial for tissue repair. A mechanism involving neuro-glial clusters and the HIF1-a/Swim/Wnt module has been identified to coordinate the activation of disseminated stem cells in injured tissue.
DEVELOPMENTAL CELL
(2022)
Article
Neurosciences
Ane Rodriguez-Bodero, Juan Manuel Encinas-Perez
Summary: Postnatal and adult neurogenesis occur in the dentate gyrus of the hippocampus in most mammals. Neural stem cells and newborn neurons serve as biosensors of hippocampal health, providing valuable information about neuronal activity and disease injuries.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Sol Beccari, Virginia Sierra-Torre, Jorge Valero, Marta Pereira-Iglesias, Mikel Garcia-Zaballa, Federico N. Soria, Laura De Las Heras-garcia, Alejandro Carretero-Guillen, Estibaliz Capetillo-Zarate, Maria Domercq, Paloma R. Huguet, David Ramonet, Ahmed Osman, Wei Han, Cecilia Dominguez, Travis E. Faust, Omar Touzani, Olatz Pampliega, Patricia Boya, Dorothy Schafer, Guillermo Marino, Emmanuelle Canet-Soulas, Klas Blomgren, Ainhoa Plaza-Zabala, Amanda Sierra
Summary: The dysfunction of microglial phagocytosis, resulting in impaired engulfment and degradation, is found in stroke and other brain disorders. This dysfunction is not explained by transcriptional changes but is related to energy depletion triggered by oxygen and nutrient deprivation. Modulating microglial autophagy may be a potential therapeutic strategy for stroke and other brain disorders.
Review
Neurosciences
Rosa C. Paolicelli, Amanda Sierra, Beth Stevens, Marie-Eve Tremblay, Adriano Aguzzi, Bahareh Ajami, Ido Amit, Etienne Audinat, Ingo Bechmann, Mariko Bennett, Frederick Bennett, Alain Bessis, Knut Biber, Staci Bilbo, Mathew Blurton-Jones, Erik Boddeke, Dora Brites, Bert Brone, Guy C. Brown, Oleg Butovsky, Monica J. Carson, Bernardo Castellano, Marco Colonna, Sally A. Cowley, Colm Cunningham, Dimitrios Davalos, Philip L. De Jager, Bart de Strooper, Adam Denes, Bart J. L. Eggen, Ukpong Eyo, Elena Galea, Sonia Garel, Florent Ginhoux, Christopher K. Glass, Ozgun Gokce, Diego Gomez-Nicola, Berta Gonzalez, Siamon Gordon, Manuel B. Graeber, Andrew D. Greenhalgh, Pierre Gressens, Melanie Greter, David H. Gutmann, Christian Haass, Michael T. Heneka, Frank L. Heppner, Soyon Hong, David A. Hume, Steffen Jung, Helmut Kettenmann, Jonathan Kipnis, Ryuta Koyama, Greg Lemke, Marina Lynch, Ania Majewska, Marzia Malcangio, Tarja Malm, Renzo Mancuso, Takahiro Masuda, Michela Matteoli, Barry W. McColl, Veronique E. Miron, Anna Victoria Molofsky, Michelle Monje, Eva Mracsko, Agnes Nadjar, Jonas J. Neher, Urte Neniskyte, Harald Neumann, Mami Noda, Bo Peng, Francesca Peri, V. Hugh Perry, Phillip G. Popovich, Clare Pridans, Josef Priller, Marco Prinz, Davide Ragozzino, Richard M. Ransohoff, Michael W. Salter, Anne Schaefer, Dorothy P. Schafer, Michal Schwartz, Mikael Simons, Cody J. Smith, Wolfgang J. Streit, Tuan Leng Tay, Li-Huei Tsai, Alexei Verkhratsky, Rommy von Bernhardi, Hiroaki Wake, Valerie Wittamer, Susanne A. Wolf, Long-Jun Wu, Tony Wyss-Coray
Summary: Microglial research has made significant progress, but the current classification system fails to accurately describe their diversity, leading to misconceptions about their functions. To address this issue, a group of multidisciplinary experts has proposed a naming framework and recommendations to help researchers better understand and describe the different states and functions of microglia.
