Re: Article: Methylating memories; the meme <--> gene link?
- --- In MindBrain@yahoogroups.com, "Robert Karl Stonjek" <stonjek@...>
quotes: "Epigenetic modification of DNA is important in memory
Might this methylation modification represent the mechanism whereby
'memes' gain access to heritable fragments of DNA in germinal cells?
Likewise, the Jacques/Monod yesteryear success in adapting bacteria to
metabolize lactose (DNA derepression?) may now be labeled a
de-methylation activation of gene responsible for lactose dehydrogenases
coding? Interesting...... Dr.d
not remember anything before the age of three. However, the brain seems
to use mechanisms important in fetal development for lifelong learning
and memory. During mitosis, epigenetic modifications, including DNA
methylation, enable parent cells to pass phenotypes on to daughter
cells. Now Miller and Sweatt report that methylation of DNA is important
for memory formation in a recent article in Neuron.
>physically blocking transcription factor binding to DNA. DNA
> The addition of methyl groups to DNA suppresses gene expression by
methyltransferase adds methyl groups to cytosine-guanine nucleotide
>during memory formation in the adult hippocampus. In contextual fear
> The authors found increased expression of DNA methyltransferases
conditioning, animals learn to associate a shock with an environment.
When they are returned to the shock environment, rats freeze with fear.
Thirty minutes after contextual fear training, rats showed increased
hippocampal expression of mRNA encoding the DNA methyltransferases (3a
and 3b) that are important during development.
>authors infused DNA methyltransferase inhibitors or vehicle into the
> Inhibition of DNA methyltransferases blocked memory formation. The
hippocampus following training and tested freezing in the shock
environment 24 hours later. Rats treated with inhibitors showed reduced
freezing relative to rats treated with vehicle. DNA methyltransferase
inhibitors did not permanently impair memory formation. After testing,
the authors retrained the rats. Twenty-four hours later, rats that had
previously been treated with DNA methyltransferase inhibitors showed
freezing comparable to vehicle-treated rats tested 24 hours after
>inhibition increases long-term potentiation and associative learning.
> Protein phosphatase 1 (PP1) suppresses memory formation, and PP1
The authors used methylation-specific real-time PCR to quantify
methylated and unmethylated PP1 after contextual fear conditioning. One
hour after training, rats trained to associate a shock with an
environment showed increased methylation of hippocampal PP1 relative to
rats exposed only to the shock or the shock environment and reduced
expression of PP1 mRNA relative to rats exposed only to the shock
environment. Relative to vehicle-treated controls, rats treated with DNA
methyltransferase inhibitors immediately after training showed less
methylated PP1, more unmethylated PP1 and greater expression of PP1
mRNA. Together, these data suggest that DNA methylation suppresses PP1
expression during associative learning.
>that is important in memory formation. One hour after training, rats
> Associative learning decreased methylation of reelin, another gene
trained to associate shock with an environment showed less methylated
and more unmethylated reelin DNA relative to rats exposed only to shock
or the shock environment and increased reelin mRNA expression relative
to rats exposed only to the shock environment.
>untrained rats, suggesting that methylation of PP1 in the adult
> DNA methyltransferase inhibition did not alter PP1 mRNA expression in
hippocampus is specific to memory formation. Expression of both PP1 and
reelin returned to baseline levels within 24 hours of contextual fear
conditioning training, suggesting that regulation of DNA methylation is
both rapid and dynamic.
>protein 2 (MeCP2), which binds to methylated DNA, and schizophrenia is
> Rett syndrome is associated with mutations in methyl-CpG-binding
associated with hypermethylation of reelin, suggesting that disruption
of DNA methylation can result in neurological disorders that impair
memory and cognition.
>regulates memory formation. Neuron 53, 857-870 (2007).
> Author: Debra Speert
> 1.. Miller, C. A. and Sweatt, J. D. Covalent modification of DNA
> Source: Nature
> Posted by
> Robert Karl Stonjek