33 replies to this topic

[neuralis]

Most of the adult neurogenesis takes place in hippocampus. There are drugs that trigger growth of new neurons in hippocampus.
Is there any agents available that promote neurogenesis in prefrontal cortex?

[Flex]

As far as I know there are just two areas that contain Stem cells or Oligodendrocyte progenitor:

The Hippocampus and the Subventricular zone.

 

Therefore, You wont supposedly find anything what affects the neurogenesis in the PFC,

since there are no cells that differate into Neurons or glial cells.

 

I believe to heard once about stemcells in the Cortex, but I cant find it and I´m not quiet sure about it.

Nevetheless, afaik some of the generated cells in the mentioned areas do migrate into other Brain areas

but in a low quantity.

Cerebrolysin as an example does increase this migration, but I dont know to what extend.

 

Btw, You can look for Your self whether there are Oligodendrocyte progenitor cells in the PFC.

 

 

 

 

[medievil]

Id gues cerebrolysin would be your best bet.

[FW900]

Strong NMDAr antagonist in lower dosages have been found to increase connectivity between the hippocampus and the PFC and induce synaptogenesis within the PFC.

 

 

 

 

A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists.

 

Molecular and cellular studies have demonstrated opposing actions of stress and antidepressant treatment on the expression of neurotrophic factors, particularly brain-derived neurotrophic factor, in limbic structures of the brain. These changes in neurotrophic factor expression and function result in structural alterations, including regulation of neurogenesis, dendrite length and spine density in hippocampus and prefrontal cortex (PFC). The deleterious effects of stress could contribute to the reduced volume of these brain regions in depressed patients. Conversely, the actions of antidepressant treatment could be mediated in part by blocking or reversing the atrophy caused by stress and depression. Recent studies have identified a novel, rapid-acting antidepressant, ketamine, in treatment-resistant depressed patients that addresses the limitations of currently available agents (i.e. delayed onset of action and low response rates). We have found that ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, causes a rapid induction of synaptogenesis and spine formation in the PFC via stimulation of the mammalian target of the rapamycin signalling pathway and increased synthesis of synaptic proteins. These effects of ketamine rapidly reverse the atrophy of PFC neurons caused by chronic stress and correspond to rapid behavioural actions of ketamine in models of depression. Characterization of a novel signalling pathway also identifies new cellular targets that could result in rapid and efficacious antidepressant actions without the side effects of ketamine.

 

Sub-anesthetic ketamine modulates intrinsic BOLD connectivity within the hippocampal-prefrontal circuit in the rat.

 

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

[medicineman]

I thought of using Very low dose ketamine every night, but this study worried me a bit.


Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats

Edited by medicineman, 24 July 2014 - 11:45 PM.

[FW900]

I thought of using Very low dose ketamine every night, but this study worried me a bit.


Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats

 

It is important to keep in mind the age of the rats in the study you linked. "7-day-old rats were injected with 40 mg/kg".  It would be the equivalent of giving a human toddler 7mg/kg. A range of substances are known to cause exponentially more damage to the developing brain compared to the fully developed brain. Even alcohol, can produce similar effects on neonatal mice Tau phosphorylation and cleavage in ethanol-induced neurodegeneration in the developing mouse brain

 

I would not be too concerned over the study.

[neuralis]

I will very soon have unlimited access to ketamine, so I will give it a go.

But before starting messing around with something so potentially dangerous as ketamine, I would like to give dihexa a try. It looks much more promising.

[Flex]

I will very soon have unlimited access to ketamine, so I will give it a go.

But before starting messing around with something so potentially dangerous as ketamine, I would like to give dihexa a try. It looks much more promising.

 

Dont want to be a scare monger and all what I can say is from my amateurish knowledge and some recherche,

but Dihexa could be a good Cancer promoter.

If You type the targets of dihexa namely: C-met or Hgf in the searchbar of Ncbi pubmed, You will get a lot of cancer results.

 

As I said I´m no Doctor and thus I cant estimate the Probabillity of its cancer effects, but at least I do rather avoid it.

[FW900]

I will very soon have unlimited access to ketamine, so I will give it a go.

But before starting messing around with something so potentially dangerous as ketamine, I would like to give dihexa a try. It looks much more promising.

 

 

Ketamine is widely used and studied in both humans and animals and its toxicity profile is well known. The only serious concern you have is the potential for bladder damage. As Flex has pointed out, Dihexa is a gamble, there is very little published information on toxicity. I'd argue that Dihexa is the substance to be concerned over being potentially dangerous not ketamine.

[Sciencyst]

That is very misinformative. Ketamine has the potential to cause long term brain damage including lesions http://www.ncbi.nlm....ubmed/23882190/

Stay far away from it is my advice.

[FW900]

That is very misinformative. Ketamine has the potential to cause long term brain damage including lesions http://www.ncbi.nlm....ubmed/23882190/

Stay far away from it is my advice.

 

Not misinformative in the slightest, it does have evidence of making positive neuronal connections to the PFC, what the topic is about. What you've stated is misinformative, by deducting from a single study, that ketamine causes long term brain damage. I could have linked 10 or more studies indicating that it mediates neuroprotection, yet I would not go as far as saying go ahead, take it like candy.

 

Everything is dose-dependent. There is a large difference between taking something at an extremely low dose for a medical or nootropic reason and completely over doing it. We are not discussing banging ketamine for dissociative effects and taking it like addicts like the people in the study, we are talking about low-dose ketamine and or other NMDAr antagonists for PFC regeneration.

 

The pro-BDNF effects and synaptogenesis would be worth the potential neurotoxicity for some individuals. There are ways (alpha 2 agonists for instance) to mitigate some of the neurotoxicity induced by ketamine. All evidence on it causing brain damage in low dosages is scant, and that which does exist (in low dosages), vacuoles are reversible.

[FW900]

 

Methylphenidate and Atomoxetine Enhance Prefrontal Function Through α₂-Adrenergic and Dopamine D₁ Receptors

This study examined the effects of the attention-deficit/hyperactivity disorder treatments, methylphenidate (MPH) and atomoxetine (ATM), on prefrontal cortex (PFC) function in monkeys and explored the receptor mechanisms underlying enhancement of PFC function at the behavioral and cellular levels.

 

Method

Monkeys performed a working memory task after administration of a wide range of MPH or ATM doses. The optimal doses were challenged with the α₂-adrenoceptor antagonist, idazoxan, or the D₁ dopamine receptor antagonist, SCH23390 (SCH). In a parallel physiology study, neurons were recorded from the dorsolateral PFC of a monkey performing a working memory task. ATM, SCH, or the α₂ antagonist, yohimbine, were applied to the neurons by iontophoresis.

Results

 

MPH and ATM generally produced inverted-U dose-response curves, with improvement occurring at moderate doses, but not at higher doses. The beneficial effects of these drugs were blocked by idazoxan or SCH. At the cellular level, ATM produced an inverted-U dose-response effect on memory-related firing, enhancing firing for preferred directions (increasing “signals”) and decreasing firing for the nonpreferred directions (decreasing “noise”). The increase in persistent firing for the preferred direction was blocked by yohimbine, whereas the suppression of firing for the nonpreferred directions was blocked by SCH.

Conclusions

 

Optimal doses of MPH or ATM improved PFC cognitive function in monkeys. These enhancing effects appeared to involve indirect stimulation of α₂ adrenoceptors and D₁ dopamine receptors in the PFC. These receptor actions likely contribute to their therapeutic effects in the treatment of attention-deficit/hyperactivity disorder.

 

http://www.ncbi.nlm....les/PMC2999884/

 

Edited by FW900, 01 August 2014 - 04:52 AM.

[Flex]

Found this:

 

An Herbal Nasal Drop Enhanced Frontal and Anterior Cingulate Cortex Activity

http://www.ncbi.nlm....les/PMC3140066/

 

..Initial clinical observations on the herbal nasal drop on patients with different brain disorders, including patients with brain tumor, mental retardation and schizophrenia, have found positive effects. This is especially encouraging as no western drug intervention is presently available for cognitive impairment resulting from brain disorders. Patients being administered the herbal remedy have demonstrated 20%–80% improvement in their conditions..

 

...Initial findings indicated that the treatment group, as compared with the control group, showed significantly greater improvement in spontaneous speech output (mean score: treatment group = 2.24, control group = 0.09, P < .01), inhibition on repetitive speech (mean score: treatment group = 1.14, control group = 0, P < .05) and initiation of behavior (mean score: treatment group = 2.6, control group = 0.33, P < .05)...

 

..Some major ingredients include Herba Artemisiae Annuae, Rhizoma Coptidis and Borneol, in a ratio of 1 : 1 : 0.5

-------

 

Unfortunaetly, I cant tell the remaining unknown compounds nor whether they are crucial...

Edited by Flex, 21 March 2015 - 02:43 PM.

[matter_of_time]

1. The most important you can do to keep your prefrontal cortex young and healty is daily activity (exercise) of 30 minutes (not 5 x 6 minutes) in moderate intensity.

2. 15 minutes daily meditation

3. Cerebrolysin

Daily activity of 30 minutes is not something you can do without. More then half of the population (wild guess) dont get enough exercise. A daily walk of 40 minutes will help propably a lot of the people around here.

[normalizing]

people are still freaked out by the pig brains in cerebrolysin. and i say, with good reason. pigs are fucking filthy animals with very questionable efficiency when it comes to their brains which are usually flooded with prions.

[Metagene]

people are still freaked out by the pig brains in cerebrolysin. and i say, with good reason. pigs are fucking filthy animals with very questionable efficiency when it comes to their brains which are usually flooded with prions.

I can't really fault your logic.

If you want to see how the sausage is made:

http://www.google.co...03333941A?cl=en

[Flex]

Found the following but correct me if I´m wrong because it looks to me that there are Stemcells in various brain areas in humans:

 

Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain

 

Abundant production of new neurons in the adult mammalian brain is limited to the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles in the forebrain (Alvarez-Buylla and Lim, 2004; Thored et al., 2007; Frielingsdorf et al., 2004; Hermann et al., 2009; Zhao et al., 2003).

Neurogenesis may be evoked in quiescent regions, but the number of persisting new neurons that are generated remains low and consequently the functional recovery of the animals limited

(Lindvall et al.,2004).

http://dev.biologist...127.full#ref-24

 

Lindvall et al.,2004:

 

Stem cell therapy for human neurodegenerative disorders–how to make it work

http://www.nature.co...ull/nm1064.html

 

[crazepharmacist]

Why are you messing with ketamine when memantine is basically the same thing only much, much safer?

[Irishdude]

Why are you messing with ketamine when memantine is basically the same thing only much, much safer?

May I ask how you formed this opinion? 

 

 

Edited by Irishdude, 17 May 2015 - 09:52 PM.

[atrw55]

decrease or increase carnitine dopamine levels in frontal cortex?

Carnitine make me impulsive, i think it decrease

 

[BieraK]

According with this study is possible to produce new neurons in the cortex of rats with Fluoxetine, this can be similar in humans
 

 

http://www.nature.co.../npp20132a.html

 

 

Adult neurogenesis in the hippocampal subgranular zone (SGZ) and the anterior subventricular zone (SVZ) is regulated by multiple factors, including neurotransmitters, hormones, stress, aging, voluntary exercise, environmental enrichment, learning, and ischemia. Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) modulates adult neurogenesis in the SGZ, the neuronal area that is hypothesized to mediate the antidepressant effects of these substances. Layer 1 inhibitory neuron progenitor cells (L1-INP cells) were recently identified in the adult cortex, but it remains unclear what factors other than ischemia affect the neurogenesis of L1-INP cells. Here, we show that chronic treatment with an SSRI, fluoxetine (FLX), stimulated the neurogenesis of γ-aminobutyric acid (GABA)ergic interneurons from L1-INP cells in the cortex of adult mice. Immunofluorescence and genetic analyses revealed that FLX treatment increased the number of L1-INP cells in all examined cortical regions in a dose-dependent manner. Furthermore, enhanced Venus reporter expression driven by the synapsin I promoter demonstrated that GABAergic interneurons were derived from retrovirally labeled L1-INP cells. In order to assess if these new GABAergic interneurons possess physiological function, we examined their effect on apoptosis surrounding areas following ischemia. Intriguingly, the number of neurons expressing the apoptotic marker, active caspase-3, was significantly lower in adult mice pretreated with FLX. Our findings indicate that FLX stimulates the neurogenesis of cortical GABAergic interneurons, which might have, at least, some functions, including a suppressive effect on apoptosis induced by ischemia.

Neurogenesis also occurs in the Hypothalamus:

http://www.sciencedi...09130221300023X

 

Adult-born new neurons are continuously added to the hippocampus and the olfactory bulb to serve aspects of learning and perceptual functions. Recent evidence establishes a third neurogenic niche in the ventral hypothalamic parenchyma surrounding the third ventricle that ensures the plasticity of specific brain circuits to stabilize physiological functions such as the energy-balance regulatory system. Hypothalamic lesion studies have demonstrated that regions associated with reproduction-related functions are also capable of recruiting newborn neurons to restore physiological functions and courtship behavior. Induced by lesion or other stimulation, elevated neurotrophic factors trigger neurogenic cascades that contribute to remodeling of certain neural circuits to meet specific transient functions. This insight raises the possibility that event-specific changes, such as increased GnRH, may be mediated by courtship-sensitive neurotrophic factors. We will discuss the potentially integral and ubiquitous roles of neurogenesis in physiological and biological phenomena, roles that await future experimental exploration.

Adult neurogenesis in the hypothalamus: evidence, functions, and implications

http://www.ncbi.nlm....pubmed/21495965

 

IGF-I stimulates neurogenesis in the hypothalamus of adult rats.

http://www.ncbi.nlm....pubmed/20525067

 

--------------------------------------------------------------------------------------------------------------------------------------------------------------------

 

Elizabeth Gould has carried out research about neurogenesis in brain areas different from hippocampus, for example neurogenesis in the neocortex, however that evidence is controversial, here are some studies:

Neurogenesis in Adult Mammals: Some Progress and Problems

http://www.jneurosci...t/22/3/619.full

 

Adult-generated hippocampal and neocortical neurons in macaques have a transient existence

http://www.pnas.org/...pe2=tf_ipsecsha

 

Neurogenesis in the neocortex of adult primates.

http://www.ncbi.nlm....pubmed/10521353

 

--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

 

The other approach is to generate new neurons is by transformin glial cells into functional neurons via SOX-2 activation:

 

 

Reprogramming 'support cells' into neurons could repair injured adult brains

The cerebral cortex lacks the ability to replace neurons that die as a result of Alzheimer's, stroke, and other devastating diseases. A new study shows that a Sox2 protein, alone or in combination with another protein, Ascl1, can cause nonneuronal cells, called NG2 glia, to turn into neurons in the injured cerebral cortex of adult mice. The findings reveal that NG2 glia represent a promising target for neuronal cell replacement strategies to treat brain injury.

http://www.scienceda...41120123136.htm

 

In vivo reprogramming of astrocytes to neuroblasts in the adult brain.

http://www.ncbi.nlm....pubmed/24056302

 

 

Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

http://www.ncbi.nlm....les/PMC4264057/

 

In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model.

http://www.ncbi.nlm....ubmed/24360883/

 

Generation of induced neurons via direct conversion in vivo.

http://www.ncbi.nlm....ubmed/23530235/

Edited by BieraK, 11 July 2015 - 04:48 AM.

[BieraK]

More about SOX-2

This looks exciting 

http://www.ncbi.nlm....pubmed/24569435

In vivo conversion of astrocytes to neurons in the injured adult spinal cord.

Abstract

Spinal cord injury (SCI) leads to irreversible neuronal loss and glial scar formation, which ultimately result in persistent neurological dysfunction. Cellular regeneration could be an ideal approach to replenish the lost cells and repair the damage. However, the adult spinal cord has limited ability to produce new neurons. Here we show that resident astrocytes can be converted to doublecortin (DCX)-positive neuroblasts by a single transcriptionfactor, SOX2, in the injured adult spinal cord. Importantly, these induced neuroblasts can mature into synapse-forming neurons in vivo. Neuronal maturation is further promoted by treatment with a histone deacetylase inhibitor, valproic acid (VPA). The results of this study indicate that in situ reprogramming of endogenous astrocytes to neurons might be a potential strategy for cellular regeneration after SCI.

 

 

 

What is needed for the activation of Sox-2???

Edited by BieraK, 11 July 2015 - 04:49 AM.

[BieraK]

Found the following but correct me if I´m wrong because it looks to me that there are Stemcells in various brain areas in humans:

 

Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain

 

Abundant production of new neurons in the adult mammalian brain is limited to the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles in the forebrain (Alvarez-Buylla and Lim, 2004; Thored et al., 2007; Frielingsdorf et al., 2004; Hermann et al., 2009; Zhao et al., 2003).

Neurogenesis may be evoked in quiescent regions, but the number of persisting new neurons that are generated remains low and consequently the functional recovery of the animals limited

(Lindvall et al.,2004).

http://dev.biologist...127.full#ref-24

 

Lindvall et al.,2004:

 

Stem cell therapy for human neurodegenerative disorders–how to make it work

http://www.nature.co...ull/nm1064.html

Yes, there are stem cells in various brain areas in humans
 

Adult Neurogenesis in the Central and Peripheral Nervous Systems

http://www.ncbi.nlm....les/PMC3395800/

Similar to the SVZ, different types of NSCs exist along the ventricular system, including the 3rd and 4th ventricles of the brain, and the central canal of the spinal cord [10-12]. However, NSCs in these regions appear to be quiescent, and they neither proliferate nor spontaneously produce new neurons in the adult brain [3]. An extended and collapsed area of lateral ventricles called the subcallosal zone (SCZ) also contains NSCs that have the potential to produce neuroblasts [13]. Recently, we found that newly produced neuroblasts in the SCZ fail to mature into functional neurons and undergo massive programmed cell death [14]. Thus, gene knockout of Bax, a pro-apoptotic gene, completely rescues SCZ neuroblasts from death and results in the generation of neurons. This result indicates that the SCZ does not provide a sufficient environment for the maturation of neuroblasts into neurons.

 

Edited by BieraK, 11 July 2015 - 04:23 AM.

[resveratrol_guy]

What is needed for the activation of Sox-2???

 

Since this is an oncogene, you might have better luck activating RepSox (E616452) instead. It sounds like this is an artificial Sox2 analog.

[opusensemble]

I'm placing this here as it may be somewhat related. 
 

I am 38 years old, and am struggling with severe and debilitating treatment resistant depression for about 3 years. 

My main physical symptom since this started has been a constant and unrelenting acid burning/numbing on my left frontal lobe.

This sensation is so debilitating that has me bed-bound 90%+ of the time as gives me some degree of movement and balance difficulties, partial numbness on the left side of my face and memory and cognitive confusion.

 

I have done a MRI scan on 2014, about 8 months after the onset of the symptoms, and the report came normal at the time.

 

Considering the severity of the physical symptoms in my brain, I am wondering if I have any form of frontal lobe atrophy or degenerative condition: http://www.alzheimer...-lobe-dementia/

 

My layman interpretation of the exam shows the existence of a noticeable "gap" between the frontal lobes and the skull bone, 

specially visible in the sagital and axial MRI cuts, suggesting that an atrophy has been taking place: 

 

http://tinyurl.com/mri-sagital

http://tinyurl.com/mri-axial

http://tinyurl.com/mri-coronal

 

Do you think, that attending to my executive functioning impairment this is likely to be a case of frontal lobe atrophy?

 

[gamesguru]

In this case, increased activity would be healthy, stimulate nerve growth, branching, connectivity[!].

green tea extract increased activation in the DLPFC relative to a control condition (FWE P<0.001). This neural effect was related to green tea dosage.

Conclusions:
These data suggest that green tea extract may modulate brain activity in the DLPFC, a key area that mediates working memory processing in the human brain. Moreover, this is the first neuroimaging study implicating that functional neuroimaging methods provide a means of examining how green tea extract acts on the brain.

→   Neural effects of green tea extract on dorsolateral prefrontal cortex

 

[dreamwolf]

Has anyone heard of T-817MA? It appears to be able to remedy the loss of the parvalbumin containing gaba neurons in the prefrontal cortex.

New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function.
Uehara T1, Sumiyoshi T, Kurachi M.
Author information
Abstract
Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia.
PMID: 26630957 PMCID: PMC4759318

Currently in Phase 2 studies for Alzheimer's

[Flex]

Has anyone heard of T-817MA? It appears to be able to remedy the loss of the parvalbumin containing gaba neurons in the prefrontal cortex.

New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function.
Uehara T1, Sumiyoshi T, Kurachi M.
Author information
Abstract
PMID: 26630957 PMCID: PMC4759318

Currently in Phase 2 studies for Alzheimer's

 

Looks nice but be allways aware that You dont know the side-effects. some of them might be persitent due to an unknown mechanism like e.g. epigenetic or positive or negative feed-forward loop.
it´s not quiet easy (i.e. has potential for a years long journey) to find out what it is and how to reverse it...

 

Edit: no scare mongering but take it as a suggestion to request the possible dangers of an unknown substance at e.g. reddit/askscience.

Edited by Flex, 28 August 2016 - 11:29 PM.

[BieraK]

https://www.ncbi.nlm...pubmed/26701067

 

Stem Cells. 2016 Apr;34(4):888-901. doi: 10.1002/stem.2276. Epub 2016 Jan 19.
Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

Kim JY1, Choi K2, Shaker MR1, Lee JH1, Lee B1, Lee E1, Park JY3, Lim MS4,5, Park CH4,5,6, Shin KS2, Kim H1, Geum D7, Sun W1.

Author information

 

Abstract

Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy.

BDNF is easy to induce, several compound can do that: Noopept, P21, Semax, Polygala Tenuifolia, Curcumin.
Somebody know something about Bcl-xL?

Edited by BieraK, 07 January 2017 - 11:23 PM.

[gamesguru]

Bcl-xL is an endogenous agent regulating apoptosis of brain cell and mitochondria

 

quercetin and EGCG appear to regulate it.  given the quantity of tea and red onion in my diet, my level of stupidity is shocking to say the least

Polyphenolic Flavonoids Differ in Their Antiapoptotic Efficacy in Hydrogen Peroxide–Treated Human Vascular Endothelial Cells

1.       Yean-Jung Choi, 

2.       Jung-Sook Kang^*, 

3.       Jung Han Yoon Park, 

4.       Yong-Jin Lee,

5.       Jung-Suk Choi, and 

6.       Young-Hee Kang²

Abstract

Oxidative injury induces cellular and nuclear damage that leads to apoptotic cell death. Agents or antioxidants that can inhibit production of reactive oxygen species can prevent apoptosis. We tested the hypothesis that flavonoids can inhibit H₂O₂-induced apoptosis in human umbilical vein endothelial cells. A 30-min pulse treatment with 0.25 mmol/L H₂O₂ decreased endothelial cell viability within 24 h by ∼40% (P < 0.05) with distinct nuclear condensation and DNA fragmentation. In the H₂O₂ apoptosis model, the addition of 50 μmol/L of the flavanol (-)epigallocatechin gallate and the flavonol quercetin, which have in vitro radical scavenging activity, partially (P < 0.05) restored cell viability with a reduction in H₂O₂-induced apoptotic DNA damage. In contrast, the flavones, luteolin and apigenin, at the nontoxic dose of 50 μmol/L, intensified cell loss (P < 0.05) after exposure to H₂O₂ and did not protect cells from oxidant-induced apoptosis. The flavanones, hesperidin and naringin, did not have cytoprotective effects. The antioxidants, (-)epigallocatechin gallate and quercetin, inhibited endothelial apoptosis, enhanced the expression of bcl-2 protein and inhibited the expression of bax protein and the cleavage and activation of caspase-3. Therefore, flavanols and flavonols, in particular (-)epigallocatechin gallate and quercetin, qualify as potent antioxidants and are effective in preventing endothelial apoptosis caused by oxidants, suggesting that flavonoids have differential antiapoptotic efficacies. The antiapoptotic activity of flavonoids appears to be mediated at the mitochondrial bcl-2 and bax gene level.

 

accidentally churned up this little nugget

 

EBioMedicine. 2015 Jul 7;2(8):898-908. doi: 10.1016/j.ebiom.2015.06.023. eCollection 2015.

Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation.

Etiévant A1, Oosterhof C2, Bétry C3, Abrial E3, Novo-Perez M3, Rovera R3, Scarna H3, Devader C4, Mazella J4, Wegener G5, Sánchez C6, Dkhissi-Benyahya O3, Gronfier C3, Coizet V7, Beaulieu JM8, Blier P2, Lucas G9, Haddjeri N3.

Abstract

Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.