8 replies to this topic

[Infinite1]

Mostly just doing a cut and past of this from Neuroscience news, no time to fully digest the full text. Full text is available at: http://www.cell.com/...09(15)00419-1. 

 

I will be looking into NeuroD1 and NEUROGENIN/2, definitively a very promising however still only in vetro and in mouse models.

 

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Summary
We have recently demonstrated that reactive glial cells can be directly reprogrammed into functional neurons by a single neural transcription factor, NeuroD1. Here we report that a combination of small molecules can also reprogram human astrocytes in culture into fully functional neurons. We demonstrate that sequential exposure of human astrocytes to a cocktail of nine small molecules that inhibit glial but activate neuronal signaling pathways can successfully reprogram astrocytes into neurons in 8-10 days. This chemical reprogramming is mediated through epigenetic regulation and involves transcriptional activation of NEUROD1 and NEUROGENIN2. The human astrocyte-converted neurons can survive for >5 months in culture and form functional synaptic networks with synchronous burst activities. The chemically reprogrammed human neurons can also survive for >1 month in the mouse brain in vivo and integrate into local circuits. Our study opens a new avenue using chemical compounds to reprogram reactive glial cells into functional neurons.

 

“Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons” by Lei Zhang, Jiu-Chao Yin, Hana Yeh, Ning-Xin Ma, Grace Lee, Xiangyun Amy Chen, Yanming Wang, Li Lin, Li Chen, Peng Jin, Gang-Yi Wu, and Gong Chen in Cell Stem Cell. Published online October 15 2015 doi:10.1016/j.stem.2015.09.012

 

 

[gamesguru]

Wow, interesting!  (At first I read the title and assumed, oh the poor idiot confused astrocytes and neurons. Made an ass of myself.)

Not sure if they reach the brain, or how strong an influence they exert, or even if it's the same gene in the brain, but I found two natural products:

Promotion of β-cell differentiation by the alkaloid conophylline in porcine pancreatic endocrine cells.
We previously found that conophylline, an alkaloid isolated from the leaves of Ervatamia microphylla, induced beta-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured fetal rat pancreatic tissue and that it also decreased the blood glucose level in streptozotocin-treated fetal rats. In the present research, we looked into the effect of conophylline on the differentiation of newborn pig pancreatic endocrine cells into insulin-secreting cells. Conophylline potentiated the differentiation of monolayer cells into insulin-producing cells in the presence of nicotinamide in 3 weeks. Next we prepared islet-like cell clusters (ICC). Cononophylline together with nicotinamide also increased the number of insulin-producing cells and the insulin content in ICC in 3-6 weeks. The ICC thus prepared were sensitive to the glucose concentration for the insulin secretion. Conophylline increased the mRNA expression of PDX-1, neurogenin3, neuroD/Beta2, and insulin in ICC. Thus, the vinca alkaloid conophylline potentiated beta-cell differentiation in porcine pancreatic endocrine-rich cells in cluster cultures. Pig pancreatic cells are practical candidate for use in transplantation therapy. Conophylline may thus be useful for the large-scale preparation of porcine insulin-producing cells for the regeneration therapy of type-1 diabetes mellitus.

Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-stat3 and bHLH family protein expression.
Signal transducer and activator of transcription 3 (stat3) and basic helix-loop-helix (bHLH) gene family are important cellular signal molecules for the regulation of cell fate decision and neuronal differentiation of neural stem/progenitor cells (NPCs). In the present study, we investigated the effects of baicalin, a flavonoid compound isolated from Scutellaria baicalensis G, on regulating phosphorylation of stat3 and expression of bHLH family proteins and promoting neuronal differentiation of NPCs. Embryonic NPCs from the cortex of E15-16 rats were treated with baicalin (2, 20 μM) for 2h and 7 days. Neuronal and glial differentiations were identified with mature neuronal marker microtubule associated protein (MAP-2) and glial marker Glial fibrillary acidic protein (GFAP) immunostaining fluorescent microscopy respectively. Phosphorylation of stat3 (p-stat3) and expressions of bHLH family genes including Mash1, Hes1 and NeuroD1 were detected with immunofluorescent microscopy and Western blot analysis. The results revealed that baicalin treatment increased the percentages of MAP-2 positive staining cells and decreased GFAP staining cells. Meanwhile, baicalin treatment down-regulated the expression of p-stat3 and Hes1, but up-regulated the expressions of NeuroD1 and Mash1. Those results indicate that baicalin can promote the neural differentiation but inhibit glial formation and its neurogenesis-promoting effects are associated with the modulations of stat3 and bHLH genes in neural stem/progenitor cells.

[gizmobrain]

Wow, interesting!  (At first I read the title and assumed, oh the poor idiot confused astrocytes and neurons. Made an ass of myself.)
Not sure if they reach the brain, or how strong an influence they exert, or even if it's the same gene in the brain, but I found two natural products:

Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-stat3 and bHLH family protein expression.
Signal transducer and activator of transcription 3 (stat3) and basic helix-loop-helix (bHLH) gene family are important cellular signal molecules for the regulation of cell fate decision and neuronal differentiation of neural stem/progenitor cells (NPCs). In the present study, we investigated the effects of baicalin, a flavonoid compound isolated from Scutellaria baicalensis G, on regulating phosphorylation of stat3 and expression of bHLH family proteins and promoting neuronal differentiation of NPCs. Embryonic NPCs from the cortex of E15-16 rats were treated with baicalin (2, 20 μM) for 2h and 7 days. Neuronal and glial differentiations were identified with mature neuronal marker microtubule associated protein (MAP-2) and glial marker Glial fibrillary acidic protein (GFAP) immunostaining fluorescent microscopy respectively. Phosphorylation of stat3 (p-stat3) and expressions of bHLH family genes including Mash1, Hes1 and NeuroD1 were detected with immunofluorescent microscopy and Western blot analysis. The results revealed that baicalin treatment increased the percentages of MAP-2 positive staining cells and decreased GFAP staining cells. Meanwhile, baicalin treatment down-regulated the expression of p-stat3 and Hes1, but up-regulated the expressions of NeuroD1 and Mash1. Those results indicate that baicalin can promote the neural differentiation but inhibit glial formation and its neurogenesis-promoting effects are associated with the modulations of stat3 and bHLH genes in neural stem/progenitor cells.

Baicalin exerts some very interesting effects because of its prolyl oligopeptidase inhibition, as well. Would be interesting to see more discussion about it.

[Flex]

Found this:

 

Highlights

    •Conversion of reactive glial cells into functional neurons in vivo using NeuroD1
    •NeuroD1 induces glia-neuron conversion in an Alzheimer’s disease mouse model
    •NeuroD1 also reprograms NG2 cells into glutamatergic and GABAergic neurons
    •Human astrocytes can also be converted into glutamatergic neurons with NeuroD1

 

In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model

http://www.cell.com/...5909(13)00550-X

 

So could something like Baicalin induce or increase the conversion of Glia to Neurons ?

 

However this Scientist shows a critical view on the neurogenesis debate

 

Adult neurogenesis 20 years later: physiological function vs. brain repair

http://journal.front...5.00071/full#B9

 

Edit: made a mistake. Neuro D1 was viraly transfected, so baicalein might not work if there arent naturally any receptors for Neuro D1

 

Edited by Flex, 18 October 2015 - 05:57 PM.

[BieraK]

https://www.ncbi.nlm...pubmed/27590267
 

Methylene Blue promotes cortical neurogenesis and ameliorates behavioral deficit after photothrombotic stroke in rats.

Ahmed ME1, Tucker D1, Dong Y1, Lu Y1, Zhao N1, Wang R1, Zhang Q2.

Author information  

 

Abstract  

Ischemic stroke in rodents stimulates neurogenesis in the adult brain and the proliferation of newborn neurons that migrate into the penumbra zone. The present study investigated the effect of Methylene Blue (MB) on neurogenesis and functional recovery in a photothrombotic (PT) model of ischemic stroke in rats. PT stroke model was induced by photo-activation of Rose Bengal dye in cerebral blood flow by cold fiber light. Rats received intraperitoneal injection of either MB (0.5mg/kg/day) from day 1 to day 5 after stroke or an equal volume of saline solution as a control. Cell proliferative marker 5-bromodeoxyuridine (BrdU) was injected twice daily (50mg/kg) from day 2 to day 8 and animals were sacrificed on day 12 after PT induction. We report that MB significantly enhanced cell proliferation and neurogenesis, as evidenced by the increased co-localizations of BrdU/NeuN, BrdU/DCX, BrdU/MAP2 and BrdU/Ki67 in the peri-infarct zone compared with vehicle controls. MB thus effectively limited infarct volume and improved neurological deficits compared to PT control animals. The effects of MB were accompanied with an attenuated level of reactive gliosis and release of pro-inflammatory cytokines, as well as elevated levels of cytochrome c oxidase activity and ATP production in peri-infarct regions. Our study provides important information that MB has the ability to promote neurogenesis and enhance the newborn-neurons' survival in ischemic brain repair by inhibiting microenvironmental inflammation and increasing mitochondrial function.

The problem with this is you need an state similar to an stroke.
So if you receive a hit in your head, go for your MB :P 

 

[BieraK]

So, talking seriously
What can be done to mimic that state? What are the specific effects of an stroke that triggers cell repair and glial cell conversion into neurons?

Perhaps a pseudo-hipoxic state could be the trick? LLLT? A prolonged session of TDCS while MB is in your body (Brain)?

Edited by BieraK, 23 October 2016 - 12:00 AM.

[psychejunkie]

https://www.jstage.j..._5_261/_article

 

 

An extract of royal jelly (RJ) significantly increased the percentage in the total cell population of not only neurons immunoreactive for class III β-tubulin (Tuj1) but also astrocytes immunoreactive for glial fibrillary acidic protein (GFAP), and oligodendrocytes immunoreactive for 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) generated from NSCs, but decreased that of nestin-positive NSCs. These results highlight a novel and outstanding property of the RJ,i.e., that it facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes). On the other hand, 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid characteristic of RJ, increased the generation of neurons and decreased that of astrocytes from NSCs. These observations suggest that RJ contains plural components that differently influence neuronal and/or glial lineages and that HDEA is one of such components of RJ that facilitates neurogenesis by NSCs.

 

[Moltic]

So Royal Jelly encourages stem cells to turn into neurons rather than glia. What's the consequences of having a higher neuron:glia ratio?

 

https://www.jstage.j..._5_261/_article

 

 

An extract of royal jelly (RJ) significantly increased the percentage in the total cell population of not only neurons immunoreactive for class III β-tubulin (Tuj1) but also astrocytes immunoreactive for glial fibrillary acidic protein (GFAP), and oligodendrocytes immunoreactive for 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) generated from NSCs, but decreased that of nestin-positive NSCs. These results highlight a novel and outstanding property of the RJ,i.e., that it facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes). On the other hand, 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid characteristic of RJ, increased the generation of neurons and decreased that of astrocytes from NSCs. These observations suggest that RJ contains plural components that differently influence neuronal and/or glial lineages and that HDEA is one of such components of RJ that facilitates neurogenesis by NSCs.

 

 

[gamesguru]

Like a major highway system with few construction workers to support it.  Without the necessary upkeep, it slowly sinks in ruins.  But it's unlikely to be that serious.  Especially if you read the study closely, you see it reports increased neurons, astrocytes, and oligodendrocytes while decreasing neural stem cells.  That's exactly what you would expect from a GDNF-stimulanting compound such as royal jelly: more stem cells going to astrocytes.  Since astrocytes are the supportive structure, maybe their generation contributes to increased neural capacity and then the nerves just fill in the new gaps, like bacteria on a new agar medium.  It's also possible this process is helped along with NGF- or BDNF-stimulanting compounds in royal jelly, e.g. AMP N1-oxide, which induces PC12 differentiation^[1].  Either way, I'm thinking the lower stem cell count is not bad, and just a sign of increased differentiation and proliferation and other cool stuff.