Astrocytes for brain repair: More than just a neuron’s sidekick

AbstractChoroid plexus (ChP), a vascularized secretory epithelium located in all brain ventricles, plays critical roles in development, homeostasis and brain repair. Reverse transcription quantitative real-time PCR (RT-qPCR) is a popular and useful technique for measuring gene expression changes and also widely used in ChP studies. However, the reliability of RT-qPCR data is strongly dependent on the choice of reference genes, which are supposed to be stable across all samples. In this study, we validated the expression of 12 well established housekeeping genes in ChP in 2 independent experimental paradigms by using popular stability testing algorithms: BestKeeper, DeltaCq, geNorm and NormFinder. Rer1 and Rpl13a were identified as the most stable genes throughout mouse ChP development, while Hprt1 and Rpl27 were the most stable genes across conditions in a mouse sensory deprivation experiment. In addition, Rpl13a, Rpl27 and Tbp were mutually among the top five most stable genes in both experiments. Normalisation of Ttr and Otx2 expression levels using different housekeeping gene combinations demonstrated the profound effect of reference gene choice on target gene expression. Our study emphasized the importance of validating and selecting stable housekeeping genes under specific experimental conditions.

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Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming

Science Advances ◽

10.1126/sciadv.abe8978 ◽

2021 ◽

Vol 7 (15) ◽

pp. eabe8978

Author(s):

Álvaro Herrero-Navarro ◽

Lorenzo Puche-Aroca ◽

Verónica Moreno-Juan ◽

Alejandro Sempere-Ferràndez ◽

Ana Espinosa ◽

...

Keyword(s):

Molecular Diversity ◽

Regional Identity ◽

Brain Regions ◽

Molecular Signature ◽

Specific Gene ◽

Thalamic Nuclei ◽

Brain Repair ◽

Cell Diversity ◽

Regional Specificity ◽

Epigenetic Signatures

Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.

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Review: Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function

Neuropathology and Applied Neurobiology ◽

10.1111/nan.12107 ◽

2014 ◽

Vol 40 (1) ◽

pp. 3-12 ◽

Cited By ~ 46

Author(s):

S. M. G. Braun ◽

S. Jessberger

Keyword(s):

Adult Neurogenesis ◽

Brain Function ◽

Normal Brain ◽

Brain Repair ◽

Neuropsychiatric Disease ◽

Normal Brain Function

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Brain Repair

Science ◽

10.1126/science.322.5903.817k ◽

2008 ◽

Vol 322 (5903) ◽

pp. 817k-817k

Keyword(s):

Brain Repair

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Hematopoietic Cell Therapy for Brain Repair

Contemporary Neuroscience - Cell Therapy, Stem Cells, and Brain Repair ◽

10.1007/978-1-59745-147-5_13 ◽

2007 ◽

pp. 341-362

Author(s):

Martina Vendrame ◽

Alison E. Willing

Keyword(s):

Cell Therapy ◽

Hematopoietic Cell ◽

Brain Repair

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XENOTRANSPLANTATION FOR BRAIN REPAIR

Transplantation Journal ◽

10.1097/00007890-200107270-00004 ◽

2001 ◽

Vol 72 (2) ◽

pp. 190-196 ◽

Cited By ~ 12

Author(s):

Thomas Brevig ◽

Morten Meyer ◽

Tom Kristensen ◽

Jens Zimmer ◽

Jan Holgersson

Keyword(s):

Brain Repair

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Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

10.1101/2020.02.10.942870 ◽

2020 ◽

Author(s):

JE Le Belle ◽

J Sperry ◽

K Ludwig ◽

NG Harris ◽

MA Caldwell ◽

...

Keyword(s):

Fatty Acids ◽

Stem Cells ◽

Stem Cell ◽

Cell Growth ◽

Olfactory Bulb ◽

Neural Stem Cells ◽

Egf Receptor ◽

Brain Repair ◽

Multipotent Stem Cells ◽

Growth And Survival

AbstractFatty acids are well known as important constituents for the synthesis of membrane lipids and as sources of cellular energy in the CNS. However, fatty acids can also act as vital second messenger molecules in the nervous system and regulate the activity of many proteins affecting cell growth and survival. Here, we show that an essential dietary fatty acid, Decosahexaenoic acid, (DHA), can enhance stem cell function in vitro and in vivo. We found that this effect is not due to an increase in the overall proliferation rate of all neural progenitors, but is due to an increase in the number of multipotent stem cells that leads to greater levels of subventricular zone (SVZ) neurogenesis with restoration of olfactory function in aged mice. These effects were likely mediated through increased EGF-receptor sensitivity, a conversion of EGRFR+ progenitors back into an EGRFR+/GFAP+ stem cell state, and the activation of the PI3K/AKT signaling pathway, which is a critical pathway in many NSC cell functions including cell growth and survival. Together these data demonstrate that neural stem cells in the aged and quiescent neurogenic niche of the mouse SVZ retain their ability to self-renew and contribute to neurogenesis when apparently rejuvenated by DHA and PI3K/AKT pathway activation. DHA stimulation of this signaling enhances the number of multipotent stem cells and neurogenesis in young and aged rodent and human stem cells and hence may have implications for the manipulation of neural stem cells for brain repair.Significance StatementWe have identified potentially important effects of DHA on the stem cell population which may be unique to the SVZ stem cell niche. Our studies demonstrate that DHA can promote the production of neural stem cells, possibly via a non-proliferative mechanism stimulated by EGF receptor activation, and prolongs their viability. Aging animals undergo an apparent loss in SVZ stem cells and an associated decline in olfactory bulb function. We find that dietary DHA supplementation at least partially restores stem cell numbers, olfactory bulb neurogenesis and olfactory discrimination and memory in aged mice, demonstrating a capacity for rejuvenation is retained despite age-related changes to the niche, which has significant implications for ameliorating cognitive decline in aging and for endogenous brain repair.

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