Effects of Dibutyryl Cyclic-AMP on Survival and Neuronal Differentiation of Neural Stem/Progenitor Cells Transplanted into Spinal Cord Injured Rats

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

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Evaluation of the effects of riluzole on adult spinal cord‐derived neural stem/progenitor cells in vitro and in vivo

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2015.08.007 ◽

2015 ◽

Vol 47 (Part_B) ◽

pp. 140-146 ◽

Cited By ~ 5

Author(s):

Laureen D. Hachem ◽

Andrea J. Mothe ◽

Charles H. Tator

Keyword(s):

Spinal Cord ◽

Progenitor Cells ◽

Neural Stem Progenitor Cells ◽

Adult Spinal Cord

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Clock genes regulate neurogenic transcription factors, including NeuroD1, and the neuronal differentiation of adult neural stem/progenitor cells

Neurochemistry International ◽

10.1016/j.neuint.2008.12.005 ◽

2009 ◽

Vol 54 (5-6) ◽

pp. 277-285 ◽

Cited By ~ 36

Author(s):

Tomomi Kimiwada ◽

Mikako Sakurai ◽

Hiroki Ohashi ◽

Shunsuke Aoki ◽

Teiji Tominaga ◽

...

Keyword(s):

Transcription Factors ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Clock Genes ◽

Neural Stem Progenitor Cells

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OBTAINING OF CELLULAR PREPARATIONS OF RAT AND HUMAN OLFACTORY MUCOSA AND THEIR INFLUENCE ON THE SIZE OF MODELED SPINAL CORD CYSTALS

BIOTECHNOLOGY: STATE OF THE ART AND PERSPECTIVES ◽

10.37747/2312-640x-2021-19-75-77 ◽

2021 ◽

Vol 1 (19) ◽

pp. 75-77

Author(s):

O.V. Stepanova ◽

E.K. Karsuntseva ◽

G.A. Fursa ◽

A.V. Chadin ◽

M.P. Valikhov ◽

...

Keyword(s):

Spinal Cord ◽

Progenitor Cells ◽

Olfactory Mucosa ◽

Olfactory Ensheathing Cells ◽

Complete Disappearance ◽

Ensheathing Cells ◽

Neural Stem Progenitor Cells ◽

Human Olfactory Mucosa ◽

Enriched Cultures

Enriched cultures of olfactory ensheathing cells and neural stem/progenitor cells were obtained according to our developed protocols from the olfactory mucosa of rat and human. It has been shown that only transplantation of human and rat olfactory ensheathing cells leads to a significant decrease in the size of cysts, as well as their complete disappearance in some animals.

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Long-Term Selective Stimulation of Transplanted Neural Stem/Progenitor Cells for Spinal Cord Injury Improves Locomotor Function

SSRN Electronic Journal ◽

10.2139/ssrn.3858060 ◽

2021 ◽

Author(s):

Momotaro Kawai ◽

Kent Imaizumi ◽

Mitsuru Ishikawa ◽

Shinsuke Shibata ◽

Munehisa Shinozaki ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Progenitor Cells ◽

Locomotor Function ◽

Selective Stimulation ◽

Cord Injury ◽

Neural Stem Progenitor Cells ◽

Stimulation Of

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Mitochondrial dysfunction-induced KDM5A degradation impairs adult hippocampal neurogenesis in Alzheimer’s disease

10.21203/rs.3.rs-114597/v1 ◽

2020 ◽

Author(s):

Dong Kyu Kim ◽

Hyobin Jeong ◽

Jingi Bae ◽

Moon-Yong Cha ◽

Moonkyung Kang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Mitochondrial Dysfunction ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Amyloid Pathology ◽

Neural Stem Progenitor Cells

Abstract Background Adult hippocampal neurogenesis (AHN) is a process of continuously generating functional mature neurons from neural stem cells in the dentate gyrus. In Alzheimer’s disease (AD) brains, amyloid pathology has deleterious effects on AHN, but molecular mechanisms for dysregulated AHN are unclear. Mitochondria of neural stem/progenitor cells play crucial roles in determining cell fate. Since mitochondrial dysfunction by amyloid pathology is the typical symptom of AD pathogenesis, we aim to study whether mitochondrial dysfunction of neural stem/progenitor cells by amyloid pathology causes the impairment of AHN, and elucidate the molecular mechanism of the phenomenon. Methods To investigate the effect of mitochondrial dysfunction of neural stem/progenitor cells on neuronal differentiation, we expressed mitochondria-targeted amyloid beta (mitoAβ) in neural stem/progenitor cells in vitro and in vivo. Proteomic analysis of the hippocampal tissue implicated mitochondrial dysfunction by mitoAβ as a cause of AHN deficits. We identified epigenetic regulators of neural progenitor cells that are regulated by mitoAβ expression or drug-induced mitochondrial toxicity and proposed a link between mitochondria and AHN. Results Amyloid pathology characteristically inhibited the neuronal differentiation stage, not the proliferation of neural stem/progenitor cells during AHN in early AD model mice. Mitochondrial dysfunction in neural stem/progenitor cells by expressing mitoAβ inhibited the neuronal differentiation and AHN with cognitive impairment. Mechanistic studies revealed that lysine demethylase 5A (KDM5A) was involved in the neuronal differentiation and could be degraded by mitochondrial dysfunction in neural progenitor cells, thereby inhibiting the differentiation and cognitive functions. Conclusions These results reveal the new role of KDM5A as a mediator of retrograde signaling, reflecting mitochondrial status, and that the decrease of KDM5A in neural progenitor cells by mitochondrial dysfunction impairs the neuronal differentiation and AHN, finally leading to memory deficits. These findings and its relationship to mitochondrial dysfunction suggest that mitochondrial failure in neural progenitor cells by amyloid pathology closely associates with reduced AHN in AD.

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