scholarly journals The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain

2010 ◽  
Vol 112 (6) ◽  
pp. 1368-1385 ◽  
Author(s):  
Patricia Mathieu ◽  
Daniela Battista ◽  
Amaicha Depino ◽  
Valeria Roca ◽  
Mariana Graciarena ◽  
...  
2020 ◽  
Author(s):  
Manuel Göpferich ◽  
Nikhil Oommen George ◽  
Ana Domingo Muelas ◽  
Alex Bizyn ◽  
Rosa Pascual ◽  
...  

SUMMARYAutism spectrum disorder (ASD) is a neurodevelopmental disease affecting social behavior. Many of the high-confident ASD risk genes relate to mRNA translation. Specifically, many of these genes are involved in regulation of gene expression for subcellular compartmentalization of proteins1. Cis-regulatory motifs that often localize to 3’- and 5’-untranslated regions (UTRs) offer an additional path for posttranscriptional control of gene expression. Alternative cleavage and polyadenylation (APA) affect 3’UTR length thereby influencing the presence or absence of regulatory elements. However, APA has not yet been addressed in the context of neurodevelopmental disorders. Here we used single cell 3’end sequencing to examine changes in 3’UTRs along the differentiation from neural stem cells (NSCs) to neuroblasts within the adult brain. We identified many APA events in genes involved in neurodevelopment, many of them being high confidence ASD risk genes. Further, analysis of 3’UTR lengths in single cells from ASD and healthy individuals detected longer 3’UTRs in ASD patients. Motif analysis of modulated 3’UTRs in the mouse adult neurogenic lineage and ASD-patients revealed enrichment of the cytoplasmic and polyadenylation element (CPE). This motif is bound by CPE binding protein 4 (CPEB4). In human and mouse data sets we observed co-regulation of CPEB4 and the CPEB-binding synaptic adhesion molecule amyloid beta precursor-like protein 1 (APLP1). We show that mice deficient in APLP1 show aberrant regulation of APA, decreased number of neural stem cells, and autistic-like traits. Our findings indicate that APA is used for control of gene expression along neuronal differentiation and is altered in ASD patients.


2021 ◽  
Vol 12 (4) ◽  
pp. 64
Author(s):  
Sahitya Chetan Pandanaboina ◽  
Ambar B. RanguMagar ◽  
Krishna D. Sharma ◽  
Bijay P. Chhetri ◽  
Charlette M. Parnell ◽  
...  

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC–Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC–Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC–Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array.


2000 ◽  
Vol 20 (10) ◽  
pp. 1393-1408 ◽  
Author(s):  
Koji Abe

Development of neuronal and glial cells and their maintenance are under control of neurotrophic factors (NTFs). An exogenous administration of NTFs protects extremely sensitive brain tissue from ischemic damage. On the other hand, it is now known that neural stem cells are present in normal adult brain, and have a potential to compensate and recover neural functions that were lost due to ischemic stroke. These stem cells are also under control of NTFs to differentiate into a certain species of neural cells. Thus, the purpose of this review is to summarize the present understanding of the role of NTFs in normal and ischemic brain and the therapeutic potential of NTF protein itself or gene therapy, and then to summarize the role of NTFs in stem cell differentiation and a possible therapeutic potential with the neural stem cells against ischemic brain injury.


2019 ◽  
Vol 29 (10) ◽  
pp. 4050-4066 ◽  
Author(s):  
Ulrika Wilhelmsson ◽  
Isabell Lebkuechner ◽  
Renata Leke ◽  
Pavel Marasek ◽  
Xiaoguang Yang ◽  
...  

Abstract The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes–/–) mice. We found that the proliferation of Nes–/– neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes–/– mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.


2012 ◽  
Vol 8 (4) ◽  
pp. 1129-1137 ◽  
Author(s):  
Jing Liu ◽  
Jackline Githinji ◽  
Bridget Mclaughlin ◽  
Kasia Wilczek ◽  
Jan Nolta

2019 ◽  
Author(s):  
Daniel Z. Radecki ◽  
Heather Messling ◽  
James R. Haggerty-Skeans ◽  
Jayshree Samanta ◽  
James L. Salzer

SUMMARYEnhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells in the sub-ventricular zone are marked by Gli1 expression and do not generate oligodendrocytes. However, in response to demyelination they migrate to lesions and differentiate into oligodendrocytes. Inhibition of Gli1 further increases their contribution to remyelination. Gli1 and Gli2 are both transcriptional effectors of the Sonic Hedgehog pathway with highly conserved domains but the role of Gli2 in remyelination by ventral neural stem cells is not clear. Here we show that while genetic ablation of Gli1 in the ventral neural stem cells increases remyelination, loss of Gli2 in these cells decreases their migration to the white matter lesion and reduces their differentiation into mature oligodendrocytes. These studies indicate Gli1 and Gli2 have distinct, non-redundant functions in NSCs, including that Gli2 is essential for the enhanced remyelination mediated by Gli1 inhibition. They highlight the importance of designing specific Gli1 inhibitors that do not inhibit Gli2 as a strategy for therapies targeting the Shh pathway.Graphical Abstract


Sign in / Sign up

Export Citation Format

Share Document