In vivo astrocyte-to-neuron reprogramming for central nervous system regeneration: a narrative review

Gao, Feng; Li, Jianjun; Talifu, Zuliyaer; Liu, Jiayi; Pan, Yunzhu; Ke, Han; Zhang, Chun-Jia; Xu, Xin; Yu, Yan; Du, Liyong

doi:10.4103/1673-5374.353482

Cited by 25 publications

(3 citation statements)

References 96 publications

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“…Many authors are exploring the potential of astrocytes to generate new neurons, however they are focused on artificial reprogramming or transdifferentiation (Talifu et al, 2022). This is the first description of this phenomenon observed in vivo in wild type animals .…”

Section: Resultsmentioning

confidence: 99%

Adult neurogenesis through glial transdifferentiation in a CNS injury paradigm

Casas-Tintó,

García-Guillen,

Losada-Pérez

2024

Preprint

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As the global population ages, the prevalence of neurodegenerative disorders is fast increasing. This neurodegeneration as well as other CNS injuries cause permanent disabilities. Thus, generation of new neurons is the rosetta stone in contemporary neuroscience.Glial cells support central nervous system (CNS) homeostasis through evolutionary conserved mechanisms. Upon damage, glial cells activate an immune and inflammatory response to clear the injury site from debris, and proliferate to restore cell number. This glial regenerative response (GRR) is mediated by the neuropil associated glia (NG) inDrosophila, equivalent to vertebrate astrocytes, oligodendrocytes (OL) and oligodendrocyte progenitor cells (OPCs). Here, we examine the contribution of NG lineages and the GRR in response to injury. The results indicate that NG exchanges identities between EG and ALG. Additionally, we found that NG cells undergo transdifferentiation to yield neurons. Moreover, this transdifferentiation increases in injury conditions. Thus, these data demonstrate that glial cells are able to generate new neurons through direct transdifferentiation. The present work makes a fundamental contribution to the CNS regeneration field and describes a new physiological mechanism to generate new neurons.

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Section: Resultsmentioning

confidence: 99%

Adult neurogenesis through glial transdifferentiation in a CNS injury paradigm

Casas-Tintó,

García-Guillen,

Losada-Pérez

2024

Preprint

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“…They upregulate multiple genes, augment cytoskeletal dimensions, extend their processes, increase glial fibrillary acidic protein expression, and enhance immunoreactivity, ultimately forming glial scars. [ 19 , 20 ] In addition, activated astrocytes release Glu, and when excess Glu binds to the extrasynaptic NMDAR (N-methyl-d-aspartate receptor), brain-derived neurotrophic factor (BDNF) synthesis is reduced, affecting neuronal integrity. [ 6 , 21 ] Stimulation of astrocytes surrounding the BBB by metabolic glutamate receptor-1 results in elevated Ca2 + levels.…”

Section: Depression and Central Nervous Inflammationmentioning

confidence: 99%

Progress of plant polyphenol extracts in treating depression by anti-neuroinflammatory mechanism: A review

Guo,

Yang

2024

Medicine

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There is a growing body of evidence supporting the involvement of central nervous system inflammation in the pathophysiology of depression. Polyphenols are a diverse group of compounds known for their antioxidative and anti-inflammatory properties. They offer a promising and effective supplementary approach to alleviating neuropsychiatric symptoms associated with inflammation-induced depression. This paper provides a summary of the potential anti-neuroinflammatory mechanisms of plant polyphenol extracts against depression. This includes direct interference with inflammatory regulators and inhibition of the expression of pro-inflammatory cytokines. Additionally, it covers downregulating the expression of pro-inflammatory cytokines by altering protein kinases or affecting the activity of the signaling pathways that they activate. These pathways interfere with the conduction of signaling molecules, resulting in the destruction and reduced synthesis of all inflammatory mediators and cytokines. This reduces the apoptosis of neurons and plays a neuroprotective role. This paper provides a theoretical basis for the clinical application of plant polyphenols.

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“…Since the discovery that ectopic transcription factor (TF) expression can drive cell fate [ 10 ], attention has been focused on developing interventions to replace lost cells in models of injury or disease. Many publications have since identified effective methods to convert somatic cells to other cell types [ 11 , 12 ], including neuronal cells, both in vitro and in vivo [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. In the context of the central nervous system (CNS), a number of groups have examined the ectopic expression of TFs in the CNS and demonstrated that proneural TFs such as Ngn2 [ 23 ] and Ascl1 [ 20 , 24 ] and the neuronal differentiation TF Neurod1 [ 25 , 26 ] can convert glial cells to neurons [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory–Motor Cortical Stroke

Livingston,

Lee,

Enbar

et al. 2024

Biomedicines

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Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate with the intention of converting astrocytes to neurons in various models of brain injury and disease. While there have been reports that question whether astrocyte-to-neuron conversion occurs in vivo, here, we have asked if ectopic expression of the transcription factor Neurod1 is sufficient to promote improved functional outcomes when delivered in the subacute phase following endothelin-1-induced sensory–motor cortex stroke. We used an adeno-associated virus to deliver Neurod1 from the short GFAP promoter and demonstrated improved functional outcomes as early as 28 days post-stroke and persisting to at least 63 days post-stroke. Using Cre-based cell fate tracking, we showed that functional recovery correlated with the expression of neuronal markers in transduced cells by 28 days post-stroke. By 63 days post-stroke, the reporter-expressing cells comprised ~20% of all the neurons in the perilesional cortex and expressed markers of cortical neuron subtypes. Overall, our findings indicate that ectopic expression of Neurod1 in the stroke-injured brain is sufficient to enhance neural repair.

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In vivo astrocyte-to-neuron reprogramming for central nervous system regeneration: a narrative review

Cited by 25 publications

References 96 publications

Adult neurogenesis through glial transdifferentiation in a CNS injury paradigm

Adult neurogenesis through glial transdifferentiation in a CNS injury paradigm

Progress of plant polyphenol extracts in treating depression by anti-neuroinflammatory mechanism: A review

Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory–Motor Cortical Stroke

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