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Advances in Research on Neurogenesis: 3rd Edition
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Advances in Research on Neurogenesis: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 5019

Special Issue Editor

Dr. Eva Terzibasi Tozzini

E-Mail Website
Guest Editor
Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples, Italy
Interests: adult neurogenesis; aging; neurodegeneration; teleost animal models marine vertebrates; neurotrophins; immunohistochemistri; in situ hybridization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Adult neurogenesis (ANG) is the process by which new functional neurons are generated from stem cells and integrated into the pre-existing neuronal networks of an adult brain. This process has been observed in all major vertebrate taxa to variable extents. In mammals, ANG is mainly limited to two main regions (i.e., the hippocampal dentate gyrus and the olfactory bulb). On the other hand, neurogenic niches are found in many areas of the brain in teleost fish, distributed along the entire rostro–caudal axis. The rate of ANG is not fixed throughout an individual’s life, but it is strongly age-dependent and can be influenced by different stimuli, such as sensory stimulation and physical activity. Moreover, ANG is involved in a wide range of neural processes, such as age-associated neurodegenerative diseases, regeneration, psychiatric disorders, and cognitive as well as affective processes, such as learning, memory, and anxiety.

We invite all scientists employing canonical and noncanonical models in the context of ANG studies to contribute to this Special Issue, in order to provide the scientific community with the most up-to-date and in-depth overview of the knowledge in this field at the cellular, molecular, and functional levels.

We welcome reviews, commentaries, and original articles that share novel data and open new perspectives on the topic at hand. Papers primarily focusing on the following subtopics are welcome:

  • ANG, neurodegeneration, and regeneration;
  • ANG and ageing;
  • ANG and psychiatric disorders;
  • ANG and cognition;
  • The evolution of adult neurogenesis in vertebrates.

Dr. Eva Terzibasi Tozzini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adult neurogenesis
  • neurodegeneration
  • aging
  • psychiatric disorders
  • cognition
  • regeneration
  • adult neurogenesis evolution

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Published Papers (4 papers)

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Research

12 pages, 5784 KiB  
Article
Tlx Promotes Stroke-Induced Neurogenesis and Neuronal Repair in Young and Aged Mice
by Dilaware Khan, Dagmar Bock, Hai-Kun Liu and Sajjad Muhammad
Int. J. Mol. Sci. 2024, 25(22), 12440; https://doi.org/10.3390/ijms252212440 - 19 Nov 2024
Viewed by 333
Abstract
Stroke is one of the leading causes of chronic disability in humans. It has been proposed that the endogenous neural stem/progenitor cells generate new neurons in the damaged area. Still, the contribution of these cells is negligible because a low number of newborn [...] Read more.
Stroke is one of the leading causes of chronic disability in humans. It has been proposed that the endogenous neural stem/progenitor cells generate new neurons in the damaged area. Still, the contribution of these cells is negligible because a low number of newborn mature neurons are formed. Tlx conventional knock-out mice, Tlx-CreERT2 mice, and Tlx-overexpressing (Tlx-OE) mice were specifically chosen for their unique genetic characteristics, which were crucial for the experiments. Permanent and transient middle cerebral artery occlusion was used to induce stroke in the mice. Immunostainings for doublecortin and GFP/BrdU/NeuN were performed to study neurogenesis and fate mapping. The rotarod test was performed to assess motor deficits. Here, we show that stroke-induced neurogenesis is dramatically increased with the additional expression of two copies of the nuclear receptor-coding gene tailless (Tlx, also known as Nr2e1), which has been shown to be a master regulator of subventricular zone (SVZ) neural stem cells (NSCs). We show that Tlx expression is upregulated after stroke, and stroke-induced neurogenesis is blocked when Tlx is inactivated. Tlx overexpression in NSCs leads to massive induction of neurogenesis via stroke. More newborn mature neurons are formed in Tlx-overexpressing mice, leading to improved coordination and motor function recovery. Most importantly, we also demonstrate that this process is sustained in aged mice, where stroke-induced neurogenesis is nearly undetectable in wild-type animals. This study provides the first stem cell-specific genetic evidence that endogenous NSCs can be exploited by manipulating their master regulator, Tlx, and thus suggests a novel therapeutic strategy for neuronal repair. Full article
(This article belongs to the Special Issue Advances in Research on Neurogenesis: 3rd Edition)
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19 pages, 6750 KiB  
Article
Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose
by Juan Suárez, Marialuisa de Ceglia, Miguel Rodríguez-Pozo, Antonio Vargas, Ignacio Santos, Sonia Melgar-Locatelli, Adriana Castro-Zavala, Estela Castilla-Ortega, Fernando Rodríguez de Fonseca, Juan Decara and Patricia Rivera
Int. J. Mol. Sci. 2024, 25(4), 1964; https://doi.org/10.3390/ijms25041964 - 6 Feb 2024
Viewed by 1323
Abstract
Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood–brain barrier and affects brain function in numerous ways, including pain [...] Read more.
Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood–brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function. Full article
(This article belongs to the Special Issue Advances in Research on Neurogenesis: 3rd Edition)
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20 pages, 10628 KiB  
Article
Astrocytes of the Anterior Commissure Regulate the Axon Guidance Pathways of Newly Generated Neocortical Neurons in the Opossum Monodelphis domestica
by Katarzyna Bartkowska, Paulina Koguc-Sobolewska, Ruzanna Djavadian and Krzysztof Turlejski
Int. J. Mol. Sci. 2024, 25(3), 1476; https://doi.org/10.3390/ijms25031476 - 25 Jan 2024
Viewed by 1115
Abstract
In marsupials, upper-layer cortical neurons derived from the progenitors of the subventricular zone of the lateral ventricle (SVZ) mature morphologically and send their axons to form interhemispheric connections through the anterior commissure. In contrast, eutherians have evolved a new extra callosal pathway, the [...] Read more.
In marsupials, upper-layer cortical neurons derived from the progenitors of the subventricular zone of the lateral ventricle (SVZ) mature morphologically and send their axons to form interhemispheric connections through the anterior commissure. In contrast, eutherians have evolved a new extra callosal pathway, the corpus callosum, that interconnects both hemispheres. In this study, we aimed to examine neurogenesis during the formation of cortical upper layers, including their morphological maturation in a marsupial species, namely the opossum (Monodelphis domestica). Furthermore, we studied how the axons of upper layers neurons pass through the anterior commissure of the opossum, which connects neocortical areas. We showed that upper-layer II/III neurons were generated within at least seven days in the opossum neocortex. Surprisingly, these neurons expressed special AT-rich sequence binding protein 2 (Satb2) and neuropilin 1 interacting protein (Nrp1), which are proteins known to be essential for the formation of the corpus callosum in eutherians. This indicates that extrinsic, but not intrinsic, cues could be key players in guiding the axons of newly generated cortical neurons in the opossum. Although oligodendrocyte precursor cells were present in the neocortex and anterior commissure, newly generated upper-layer neurons sent unmyelinated axons to the anterior commissure. We also found numerous GFAP-expressing progenitor cells in both brain structures, the neocortex and the anterior commissure. However, at P12–P17 in the opossums, a small population of astrocytes was observed only in the midline area of the anterior commissure. We postulate that in the opossum, midline astrocytes allow neocortical axons to be guided to cross the midline, as this structure resembles the glial wedge required by fibers to cross the midline area of the corpus callosum in the rodent. Full article
(This article belongs to the Special Issue Advances in Research on Neurogenesis: 3rd Edition)
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15 pages, 5466 KiB  
Article
Leptin Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells through the Cooperative Action of MAPK/ERK1/2, JAK2/STAT3 and PI3K/AKT Signaling Pathways
by Ruolan Tan, Xiaoxuan Hu, Xinyi Wang, Meiqi Sun, Zhenlu Cai, Zixuan Zhang, Yali Fu, Xinlin Chen, Jing An and Haixia Lu
Int. J. Mol. Sci. 2023, 24(20), 15151; https://doi.org/10.3390/ijms242015151 - 13 Oct 2023
Cited by 4 | Viewed by 1649
Abstract
The potential of neural stem cells (NSCs) for neurological disorders the treatment has relied in large part upon identifying the NSCs fate decision. The hormone leptin has been reported to be a crucial regulator of brain development, able to influence the glial and [...] Read more.
The potential of neural stem cells (NSCs) for neurological disorders the treatment has relied in large part upon identifying the NSCs fate decision. The hormone leptin has been reported to be a crucial regulator of brain development, able to influence the glial and neural development, yet, the underlying mechanism of leptin acting on NSCs’ biological characteristics is still poorly understood. This study aims to investigate the role of leptin in the biological properties of NSCs. In this study, we investigate the possibility that leptin may regulate the NSCs’ fate decision, which may promote the proliferation and neuronal differentiation of NSCs and thus act positively in neurological disorders. NSCs from the embryonic cerebral cortex were used in this study. We used CCK-8 assay, ki67 immunostaining, and FACS analysis to confirm that 25–100 ng/mL leptin promotes the proliferation of NSCs in a concentration-dependent pattern. This change was accompanied by the upregulation of p-AKT and p-ERK1/2, which are the classical downstream signaling pathways of leptin receptors b (LepRb). Inhibition of PI3K/AKT or MAPK/ERK signaling pathways both abolished the effect of leptin-induced proliferation. Moreover, leptin also enhanced the directed neuronal differentiation of NSCs. A blockade of the PI3K/AKT pathway reversed leptin-stimulated neurogenesis, while a blockade of JAK2/STAT3 had no effect on it. Taken together, our results support a role for leptin in regulating the fate of NSCs differentiation and promoting NSCs proliferation, which could be a promising approach for brain repair via regulating the biological characteristics of NSCs. Full article
(This article belongs to the Special Issue Advances in Research on Neurogenesis: 3rd Edition)
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