Searching for alternatives to brain regeneration

Zebrafish have superior regenerative capacity in the central nervous system (CNS) compared to mammals. In contrast, medaka were shown to have low regenerative capacity in the adult heart and larval retina, despite the well-documented high tissue regenerative ability of teleosts. Nevertheless, medaka and zebrafish share similar brain structures and biological features to those of mammals. Hence, this study aimed to compare the neural stem cell (NSC) responses and regenerative capacity in the optic tectum of adult medaka and zebrafish after stab wound injury. Limited neuronal differentiation was observed in the injured medaka, though the proliferation of radial glia (RG) was induced in response to tectum injury. Moreover, the expression of the pro-regenerative transcriptional factors ascl1a and oct4 was not enhanced in the injured medaka, unlike in zebrafish, whereas expression of sox2 and stat3 was upregulated in both fish models. Of note, glial scar-like structures composed of GFAP+ radial fibers were observed in the injured area of medaka at 14 days post injury (dpi). Altogether, these findings suggest that the adult medaka brain has low regenerative capacity with limited neuronal generation and scar formation. Hence, medaka represent an attractive model for investigating and evaluating critical factors for brain regeneration.

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Induction of Oxidative Stress and Apoptosis in the Injured Brain: Potential Relevance to Brain Regeneration in Zebrafish.

10.21203/rs.3.rs-549302/v1 ◽

2021 ◽

Author(s):

Surendra Kumar Anand ◽

Manas Ranjan Sahu ◽

Amal Chandra Mondal

Keyword(s):

Oxidative Stress ◽

Mrna Levels ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Stab Injury ◽

Zebrafish Brain ◽

Protein Levels ◽

Injured Brain ◽

Brain Regeneration ◽

The Impact

Abstract In the recent years, zebrafish, owing to its tremendous adult neurogenic capacity, has emerged as a useful vertebrate model to study brain regeneration. Recent findings suggest a significant role of the BDNF/TrkB signaling as a mediator of brain regeneration following a stab injury in the adult zebrafish brain. Since BDNF has been implicated in a plethora of physiological processes, we hypothesized that these processes are affected in the injured zebrafish brain. In this small study, we examined the indicators of oxidative stress and of apoptosis using biochemical assays, RT-PCR and IHC to reflect upon the impact of stab injury on oxidative stress levels and apoptosis in the injured adult zebafish brain. Our results indicate induction of oxidative stress in the injured adult zebrafish brain. Also, apoptosis was induced in the injured brain as indicated by increased protein levels of cleaved caspase3 as well as enhanced mRNA levels of both pro-apoptotic and anti-apoptotic genes. This knowledge contributes to the overall understanding of adult neurogenesis in the zebrafish model and raises new questions pertaining to the compensatory physiological mechanisms in response to traumatic brain injury in the adult zebrafish brain.

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Targeted Myosin-2 Inhibition Improves Brain Regeneration After Stroke by Relaxing Hypoxia-Induced Vasoconstriction in Capillaries

Biophysical Journal ◽

10.1016/j.bpj.2019.11.2439 ◽

2020 ◽

Vol 118 (3) ◽

pp. 434a-435a

Author(s):

Mate Penzes ◽

Demeter Turos ◽

Mate Winternitz ◽

Ivan Ivic ◽

Peter Toth ◽

...

Keyword(s):

Brain Regeneration

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No head regeneration here: regeneration capacity and stem cell dynamics of Theama mediterranea (Polycladida, Platyhelminthes)

Cell and Tissue Research ◽

10.1007/s00441-019-03094-8 ◽

2019 ◽

Vol 379 (2) ◽

pp. 301-321

Author(s):

Philip Bertemes ◽

Alexandra L. Grosbusch ◽

Bernhard Egger

Keyword(s):

Stem Cells ◽

Regeneration Capacity ◽

Regeneration Potential ◽

Free Living ◽

Cell Dynamics ◽

Single Exception ◽

Brain Regeneration ◽

Head Regeneration ◽

The Brain ◽

Regeneration Blastema

Abstract Research on the regeneration potential of flatworms (Platyhelminthes) has been mainly undertaken with planarians (Tricladida), where most species can regenerate a head and no proliferation takes place in the blastema, i.e. the early undifferentiated regenerative tissue. Only few studies are available for an early-branching group within the Platyhelminthes, the Polycladida. Head regeneration in polyclads is not possible, with a single exception from a study performed more than 100 years ago: Cestoplana was reported to be able to regenerate a head if cut a short distance behind the brain. Here, we show that ‘Cestoplana’ was misdetermined and most likely was the small interstitial polyclad Theama mediterranea. We revisited regeneration capacity and dynamics of T. mediterranea with live observations and stainings of musculature, nervous system, and proliferating and differentiating stem cells. In our experiments, after transversal amputation, only animals retaining more than half of the brain could fully restore the head including the brain. If completely removed, the brain was never found to regenerate to any extent. Different from planarians, but comparable to other free-living flatworms we detected cell proliferation within the posterior regeneration blastema in T. mediterranea. Similar to other free-living flatworms, proliferation did not occur within, but only outside, the differentiating organ primordia. Our results strongly imply that brain regeneration in the absence of the latter is not possible in any polyclad studied so far. Also, it appears that proliferation of stem cells within the regeneration blastema is a plesiomorphy in flatworms and that planarians are derived in this character.

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Vertebrate brain regeneration – a community effort of fate-restricted precursor cell types

Current Opinion in Genetics & Development ◽

10.1016/j.gde.2020.06.014 ◽

2020 ◽

Vol 64 ◽

pp. 101-108

Author(s):

Christian Lange ◽

Michael Brand

Keyword(s):

Cell Types ◽

Precursor Cell ◽

Vertebrate Brain ◽

Brain Regeneration ◽

Community Effort

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Planarian brain regeneration as a model system for developmental neurotoxicology

Regeneration ◽

10.1002/reg2.52 ◽

2016 ◽

Vol 3 (2) ◽

pp. 65-77 ◽

Cited By ~ 39

Author(s):

Danielle Hagstrom ◽

Olivier Cochet‐Escartin ◽

Eva‐Maria S. Collins

Keyword(s):

Model System ◽

Developmental Neurotoxicology ◽

Brain Regeneration

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Epigallocatechin-3-gallate attenuates cerebral cortex damage and promotes brain regeneration in acrylamide-treated rats

Food & Function ◽

10.1039/c6fo01823h ◽

2017 ◽

Vol 8 (6) ◽

pp. 2275-2282 ◽

Cited By ~ 10

Author(s):

Yin He ◽

Dehong Tan ◽

Yan Mi ◽

Qian Zhou ◽

Shujuan Ji

Keyword(s):

Cerebral Cortex ◽

Cell Damage ◽

Cell Regeneration ◽

Brain Regeneration

ACR increased the rate of nestin-positive cells implying that ACR caused cell damage, and EGCG decreased the rates of nestin-positive cells against ACR suggesting that EGCG may promote cell regeneration.

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GABAergic Neuronal Precursor Grafting: Implications in Brain Regeneration and Plasticity

Neural Plasticity ◽

10.1155/2011/384216 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Manuel Alvarez Dolado ◽

Vania Broccoli

Keyword(s):

Neurological Disorders ◽

Normal Function ◽

Inhibitory Neurons ◽

Synaptic Connections ◽

Cell Type Specificity ◽

Brain Regeneration ◽

Associated Functions ◽

Promising Treatment ◽

Neuronal Transplantation ◽

Near Future

Numerous neurological disorders are caused by a dysfunction of the GABAergic system that impairs or either stimulates its inhibitory action over its neuronal targets. Pharmacological drugs have generally been proved very effective in restoring its normal function, but their lack of any sort of spatial or cell type specificity has created some limitations in their use. In the last decades, cell-based therapies using GABAergic neuronal grafts have emerged as a promising treatment, since they may restore the lost equilibrium by cellular replacement of the missing/altered inhibitory neurons or modulating the hyperactive excitatory system. In particular, the discovery that embryonic ganglionic eminence-derived GABAergic precursors are able to disperse and integrate in large areas of the host tissue after grafting has provided a strong rationale for exploiting their use for the treatment of diseased brains. GABAergic neuronal transplantation not only is efficacious to restore normal GABAergic activities but can also trigger or sustain high neuronal plasticity by promoting the general reorganization of local neuronal circuits adding new synaptic connections. These results cast new light on dynamics and plasticity of adult neuronal assemblies and their associated functions disclosing new therapeutic opportunities for the near future.

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Neurogenesis in the adult Drosophila brain

Genetics ◽

10.1093/genetics/iyab092 ◽

2021 ◽

Author(s):

Kassi L Crocker ◽

Khailee Marischuk ◽

Stacey A Rimkus ◽

Hong Zhou ◽

Jerry C P Yin ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurodegenerative Diseases ◽

Glial Cells ◽

Brain Regions ◽

Adult Brain ◽

Neural Regeneration ◽

Proliferating Cells ◽

Brain Regeneration ◽

Adult Drosophila

Abstract Neurodegenerative diseases such as Alzheimer’s and Parkinson’s currently affect ∼25 million people worldwide (Erkkinen et al. 2018). The global incidence of traumatic brain injury (TBI) is estimated at ∼70 million/year (Dewan et al. 2018). Both neurodegenerative diseases and TBI remain without effective treatments. We are utilizing adult Drosophila melanogaster to investigate the mechanisms of brain regeneration with the long term goal of identifying targets for neural regenerative therapies. We specifically focused on neurogenesis, i.e. the generation of new cells, as opposed to the regrowth of specific subcellular structures such as axons. Like mammals, Drosophila have few proliferating cells in the adult brain. Nonetheless, within 24 hours of a Penetrating Traumatic Brain Injury (PTBI) to the central brain, there is a significant increase in the number of proliferating cells. We subsequently detect both new glia and new neurons and the formation of new axon tracts that target appropriate brain regions. Glial cells divide rapidly upon injury to give rise to new glial cells. Other cells near the injury site upregulate neural progenitor genes including asense and deadpan and later give rise to the new neurons. Locomotor abnormalities observed after PTBI are reversed within two weeks of injury, supporting the idea that there is functional recovery. Together, these data indicate that adult Drosophila brains are capable of neuronal repair. We anticipate that this paradigm will facilitate the dissection of the mechanisms of neural regeneration and that these processes will be relevant to human brain repair.

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