scholarly journals Role of laminin bioavailability in the astroglial permissivity for neuritic outgrowth

2002 ◽  
Vol 74 (4) ◽  
pp. 683-690 ◽  
Author(s):  
MARCIENNE TARDY
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Neurite Outgrowth ◽  
Axonal Regeneration ◽  
Glial Scar ◽  
Reactive Astrocytes ◽  
Adult Brain ◽  
Morphological Response ◽  
Phenotypic Changes ◽  
Neuritic Outgrowth

The mechanisms involved in the failure of an adult brain to regenerate post-lesion remain poorly understood. The reactive gliosis which occurs after an injury to the CNS and leads to the glial scar has been considered as one of the major impediments to neurite outgrowth and axonal regeneration. A glial scar consists mainly of reactive, hypertrophic astrocytes. These reactive cells acquire new properties, leading to A non-permissive support for neurons. Astrogial reactivity is mainly characteriized by a high overexpression of the major component of the gliofilaments, the glial fibrillary acidic protein (GFAP). This GFAP overexpression is related to the astroglial morphological response to injury. We hypothesized that modulation of GFAP synthesis, reversing the hypertrophic phenotype, might also reverse the blockage of neuritic outgrowth observed after a lesion. In this article, we review findings of our group, confirming our hypothesis in a model of lesioned neuron-astrocyte cocultures. We demonstrate that permissivity for neuritic outgrowth is related to phenotypic changes induced in reactive astrocytes transfected by antisense GFAP-mRNA. We also found that this permissivity was related to a neuron-regulated extracellular laminin bioavailability.

Axonal Regeneration: Role of the Extracellular Matrix and the Glial Scar

2009 ◽  
pp. 1173-1180
Author(s):  
J. Silver ◽  
K.P. Horn ◽  
S.A. Busch ◽  
A.L. Yonkof
Keyword(s):  
Extracellular Matrix ◽  
Axonal Regeneration ◽  
Glial Scar

scholarly journals Fibronectin supports neurite outgrowth and axonal regeneration of adult brain neurons in vitro

2012 ◽  
Vol 1453 ◽  
pp. 8-16 ◽  
Author(s):  
David A. Tonge ◽  
Hugo T. de Burgh ◽  
Reginald Docherty ◽  
Martin J. Humphries ◽  
Susan E. Craig ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Axonal Regeneration ◽  
Adult Brain ◽  
Brain Neurons

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

scholarly journals Myelin basic protein enhances axonal regeneration from neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng
Keyword(s):  
Myelin Basic Protein ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Axonal Regeneration ◽  
Neural Progenitor Cells ◽  
Basic Protein ◽  
Neural Progenitor ◽  
Dependent Manner ◽  
Cord Injury

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

scholarly journals The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke

2021 ◽  
Author(s):  
Yong-Ming Zhu ◽  
Liang Lin ◽  
Chao Wei ◽  
Yi Guo ◽  
Yuan Qin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Glial Scar ◽  
Scar Formation ◽  
Reactive Astrocytes ◽  
Interacting Protein ◽  
Protein Levels ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

scholarly journals Early Consumption of Cannabinoids: From Adult Neurogenesis to Behavior

2021 ◽  
Vol 22 (14) ◽  
pp. 7450
Author(s):  
Citlalli Netzahualcoyotzi ◽  
Luis Miguel Rodríguez-Serrano ◽  
María Elena Chávez-Hernández ◽  
Mario Humberto Buenrostro-Jáuregui
Keyword(s):  
Young Adulthood ◽  
Adult Neurogenesis ◽  
Critical Period ◽  
Consumption Rate ◽  
Behavioral Outcomes ◽  
Endocannabinoid System ◽  
Illegal Drug ◽  
Adult Brain ◽  
As Stress

The endocannabinoid system (ECS) is a crucial modulatory system in which interest has been increasing, particularly regarding the regulation of behavior and neuroplasticity. The adolescent–young adulthood phase of development comprises a critical period in the maturation of the nervous system and the ECS. Neurogenesis occurs in discrete regions of the adult brain, and this process is linked to the modulation of some behaviors. Since marijuana (cannabis) is the most consumed illegal drug globally and the highest consumption rate is observed during adolescence, it is of particular importance to understand the effects of ECS modulation in these early stages of adulthood. Thus, in this article, we sought to summarize recent evidence demonstrating the role of the ECS and exogenous cannabinoid consumption in the adolescent–young adulthood period; elucidate the effects of exogenous cannabinoid consumption on adult neurogenesis; and describe some essential and adaptive behaviors, such as stress, anxiety, learning, and memory. The data summarized in this work highlight the relevance of maintaining balance in the endocannabinoid modulatory system in the early and adult stages of life. Any ECS disturbance may induce significant modifications in the genesis of new neurons and may consequently modify behavioral outcomes.

scholarly journals AIF3 splicing switch triggers neurodegeneration

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shuiqiao Liu ◽  
Mi Zhou ◽  
Zhi Ruan ◽  
Yanan Wang ◽  
Calvin Chang ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Nuclear Translocation ◽  
Chromatin Condensation ◽  
Neuronal Cell ◽  
Adult Brain ◽  
Postmortem Brain ◽  
Mitochondrial Functions

Abstract Background Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain. Methods AIF splicing induction in brain was determined by multiple approaches including 5′ RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. The role of AIF splicing in mitochondria and neurodegeneration was determined by its biochemical properties, cell death analysis, morphological and functional alterations and animal behavior. Three animal models, including loss-of-function harlequin model, gain-of-function AIF3 knockin model and conditional inducible AIF splicing model established using either Cre-loxp recombination or CRISPR/Cas9 techniques, were applied to explore underlying mechanisms of AIF splicing-induced neurodegeneration. Results We identified a nature splicing AIF isoform lacking exons 2 and 3 named as AIF3. AIF3 was undetectable under physiological conditions but its expression was increased in mouse and human postmortem brain after stroke. AIF3 splicing in mouse brain caused enlarged ventricles and severe neurodegeneration in the forebrain regions. These AIF3 splicing mice died 2–4 months after birth. AIF3 splicing-triggered neurodegeneration involves both mitochondrial dysfunction and AIF3 nuclear translocation. We showed that AIF3 inhibited NADH oxidase activity, ATP production, oxygen consumption, and mitochondrial biogenesis. In addition, expression of AIF3 significantly increased chromatin condensation and nuclear shrinkage leading to neuronal cell death. However, loss-of-AIF alone in harlequin or gain-of-AIF3 alone in AIF3 knockin mice did not cause robust neurodegeneration as that observed in AIF3 splicing mice. Conclusions We identified AIF3 as a disease-inducible isoform and established AIF3 splicing mouse model. The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves mitochondrial dysfunction and AIF3 nuclear translocation resulting from the synergistic effect of loss-of-AIF and gain-of-AIF3. Our study provides a valuable tool to understand the role of AIF3 splicing in brain and a potential therapeutic target to prevent/delay the progress of neurodegenerative diseases.

Personalizing Therapy for Metastatic Prostate Cancer: The Role of Solid and Liquid Tumor Biopsies

2017 ◽  
pp. 358-369 ◽  
Author(s):  
Terence W. Friedlander ◽  
Colin C. Pritchard ◽  
Himisha Beltran
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Tumor Tissue ◽  
Neuroendocrine Differentiation ◽  
Metastatic Tumor ◽  
Metastatic Lesion ◽  
Phenotypic Changes ◽  
Tumor Biopsies ◽  
Bioinformatic Approach

Although biopsies of metastatic prostate cancer are rarely undertaken in the clinical setting, there is increasing interest in developing personalized approaches to therapy by taking into account the genetic and phenotypic changes in an individual tumor. Indeed, analysis of metastatic prostate tumors can predict sensitivity to agents that inhibit DNA repair and resistance to novel hormonal agents, such as abiraterone and enzalutamide, and identify phenotypic changes, such as neuroendocrine differentiation, that have important clinical implications. Although obtaining metastatic tumor tissue is necessary for this genomic and molecular profiling, knowing when to biopsy, selecting the appropriate metastatic lesion, and interpreting the results are major challenges facing clinicians today. In this article, we discuss the rationale for obtaining metastatic tumor tissue, review the bioinformatic approach to analyzing these specimens, discuss the timing and approach to solid and liquid tumor biopsies, review the challenges associated with obtaining and acting on clinically relevant results, and discuss opportunities for the future.

scholarly journals Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3407 ◽  
Author(s):  
Paola Imbriani ◽  
Annalisa Tassone ◽  
Maria Meringolo ◽  
Giulia Ponterio ◽  
Graziella Madeo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Synaptic Function ◽  
Adult Brain ◽  
Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

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