LONGECITY

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After long periods of chronic stress and likely high cortisol my hippocampus has likely seen better days. Sooo I was interested in a short course of tianeptine (as has been discussed previously). I don't have the abstract in front of me, but bacopa apparently protects the hippocampus from cortisol (IIRC) and pregnenelone (thanks funkodyssey):

Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus.

Mayo W, Lemaire V, Malaterre J, Rodriguez JJ, Cayre M, Stewart MG, Kharouby M, Rougon G, Le Moal M, Piazza PV, Abrous DN.

Laboratoire de Psychobiologie des Comportements Adaptatifs, INSERM U588, Domaine de Carreire, Rue Camille Saint-Saens, 33077 Bordeaux, France.

Age-dependent cognitive impairments have been correlated with functional and structural modifications in the hippocampal formation. In particular, the brain endogenous steroid pregnenolone-sulfate (Preg-S) is a cognitive enhancer whose hippocampal levels have been linked physiologically to cognitive performance in senescent animals. However, the mechanism of its actions remains unknown. Because neurogenesis is sensitive to hormonal influences, we examined the effect of Preg-S on neurogenesis, a novel form of plasticity, in young and old rats. We demonstrate that in vivo infusion of Preg-S stimulates neurogenesis and the expression of the polysialylated forms of NCAM, PSA-NCAM, in the dentate gyrus of 3- and 20-month-old rats. These influences on hippocampal plasticity are mediated by the modulation of the gamma-aminobutyric acid receptor complex A (GABA(A)) receptors present on hippocampal neuroblasts. In vitro, Preg-S stimulates the division of adult-derived spheres suggesting a direct influence on progenitors. These data provide evidence that neurosteroids represent one of the local secreted signals controlling hippocampal neurogenesis. Thus, therapies which stimulate neurosteroidogenesis could preserve hippocampal plasticity and prevent the appearance of age-related cognitive disturbances.

Thoughts on the addition of bacopa and pregnenelone? Any other synergistic supps for this purpose? (NB: I'm not depressed).
Edited by scottl, 29 March 2006 - 12:36 PM.

As an initial comment before I do more research, if you have been under high stress for a long period of time, your pregnenolone levels may be quite depressed already. That seems to be a common denominator in various stages of adrenal fatigue, and that was the case with me. Most doctors don't bother to test for pregnenolone because they consider it to be an inactive precursor, when it is in fact a powerful neurosteroid. You might consider having a baseline test done so that you can dose supplemental pregnenolone accordingly.

Actually, you might want to get a baseline on all the key steroid hormones (dhea, test, estrogen, maybe even progesterone) also, since pregnenolone can potentially increase all of them, although at reasonable doses I doubt you'll see anything besides a small bump in DHEA and progesterone.

Thanks funk. Gonna get the bloodwork done in the next few days. Preg and the rest are covered...gotta double check if the panel includes progesterone though.

Oh and check out the DHA abstract I'm about to post.

nicergoline
ALCAR-arginate
lithium orotate
hydergine
Ashwagandha
royal jelly
lion's mane
idebonone

Here's a stack I made up for neurogenesis.

Yeah, there are alot of substances that may increase neurogenesis. Here's a surprise candidate:

Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats.

Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M, Zhang L, Chopp M.

Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich, USA.

BACKGROUND AND PURPOSE: We tested the hypothesis that sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, promotes functional recovery and neurogenesis after stroke. METHODS: Male Wistar rats were subjected to embolic middle cerebral artery occlusion. Sildenafil (Viagra) was administered orally for 7 consecutive days starting 2 or 24 hours after stroke onset at doses of 2 or 5 mg/kg per day. Ischemic rats administered the same volume of tap water were used as a control group. Functional outcome tests (foot-fault, adhesive removal) were performed. Rats were killed 28 days after stroke for analysis of infarct volume and newly generated cells within the subventricular zone and the dentate gyrus. Brain cGMP levels, expression of PDE5, and localized cerebral blood flow were measured in additional rats. RESULTS: Treatment with sildenafil significantly (P<0.05) enhanced neurological recovery in all tests performed. There was no significant difference of infarct volume among the experimental groups. Treatment with sildenafil significantly (P<0.05) increased numbers of bromodeoxyuridine-immunoreactive cells in the subventricular zone and the dentate gyrus and numbers of immature neurons, as indicated by betaIII-tubulin (TuJ1) immunoreactivity in the ipsilateral subventricular zone and striatum. The cortical levels of cGMP significantly increased after administration of sildenafil, and PDE5 mRNA was present in both nonischemic and ischemic brain. CONCLUSIONS: Sildenafil increases brain levels of cGMP, evokes neurogenesis, and reduces neurological deficits when given to rats 2 or 24 hours after stroke. These data suggest that this drug that is presently in the clinic for sexual dysfunction may have a role in promoting recovery from stroke.

PMID: 12411660 [PubMed - indexed for MEDLINE]

This is how you get your wife onboard with your supplementation hobby... throw in a little viagra for "neurogenesis" [lol]

edit: how about the author's names for this study? are they some kind of chinese scientist family? wtf

You've never heard of the (in)famous 'Zhangs'? They've got a real hard-on for research.

Hmmm... was that due to the neurogenic action of Sildenafil itself, or due to the N02 enhanceing effect, or due to the vasodilatory effect of the increased N02 ... if it;s any of the latter then you can just take Arginine Ethyl Ester for the same effect.

What dosage levels of pregnenolone produce these beneficial effects? I've seen pregnenolone on the market is this the same form as what was used in those tests? I assume the levels in the rats were much higher than is found in normal blood levels. I personally would be very hesitant to take a megadose of that or really of anything else. I would think that if you raised your levels up to those of a typical 20 year old, that should be beneficial but that may be too conservative. At least, it's unlikely to produce any negative side effects.

I did try pregnenolone a long while back for cognitive improvement. It gave me a lot of skin issue's, so I stopped using it. Already quantities less than 5 mg a day caused these problems.