New paper: Adult Hippocampal Neural Stem-Progenitor Cells in vitro are Vulnerable to the Mycotoxin Ochratoxin-A

[Guest guest]

THIS TIES A LOT OF THINGS TOGETHER..

Is it all making sense to people now?

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http://toxsci.oxfordjournals.org/cgi/content/abstract/kfm093v1

Toxicol Sci. 2007 Apr 21; [Epub ahead of print]

The common mycotoxin ochratoxin-A (OTA) accumulates in brain,

causes oxidative stress and elicits a DNA repair response that varies

across brain regions and neuronal populations. Neural stem/progenitor

cells (NSC) prepared from hippocampus of adult mouse brain were tested

for their vulnerability to the toxin in vitro. The following

measurements were made in NSC cell cultures in both proliferation and

differentiation media: a) viability (trypan blue exclusion),

proliferative activity ([3H]-thymidine uptake), c) the DNA repair

response (oxyguanosine glycosylase activity), and d) anti-oxidative

response (superoxide dismutase). Cells that had proliferated to

90-100% confluency in the presence of epidermal growth factor (EGF)

and basic fibroblast growth factor (bFGF) were induced to

differentiate by removal of the growth factors.

OTA, added to the cultures in concentrations of 0.01 to 100 µg/mL,

caused a dose- and time-dependent (6-72 hr) decrease in viability of

both proliferating and differentiating NSC. Proliferating NSC

exhibited a greater vulnerability to the toxin than differentiated

neurons despite robust DNA repair and anti-oxidative responses.

Pre-conditioning of NSC with a 12 hr incubation with the pro-oxidant

diethyl maleate increased DNA repair activity and subsequently

provided a moderate degree of neuroprotection. Overall, these results

lead to speculation that OTA exposure may contribute to impaired

hippocampal neurogenesis in vivo, resulting in depression and memory

deficits, conditions reported to be linked to mycotoxin exposure in

humans.

Key Words: neural stem/progenitor cells; hippocampus; ochratoxin-A;

mycotoxin; oxidative stress; DNA repair; 8-oxoguanine glycosylase-1

(OGG1); superoxide dismutase (SOD); diethyl maleate (DEM).

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Add stress to that mix for a deadly combination....

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Also, neurogenesis is frustrated. Is that how and why antidepressants

often don't work in people with mold illness?

I just read an interesting article on neurogenesis that gives one

possible reason why many people who are dealing with mold may have bad

luck with them. In order for them to work to actually cure depression,

they have to help the brain create new cells.

If the brain is at the same time, dealing with a toxin like OTA (which

is a mycotoxin in aspergillus/penicillium spp.) that prevents

neurogenesis, similar to the trichothecenes, the antidepressant won't

be successful in helping the brain repair itself.

For a good overview.. see this article..

The Reinvention of the Self: A mind-altering idea reveals how life

affects the brain.

http://www.seedmagazine.com/news/2006/02/the_reinvention_of_the_self.php

Excellent Wikipedia article on neurogenesis:

http://en.wikipedia.org/wiki/Neurogenesis

Another interesting Scholarpedia article on adult neurogenesis

http://scholarpedia.org/article/Adult_Neurogenesis