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After seven (7) weeks, hyperexcitability stops in ALS?

PostPosted: February 21st, 2015, 6:29 pm
by misterjuanperalta
After Seven (7) Weeks, hyperexcitability stops in ALS?

In the new study, first author Anna-Claire Devlin and colleagues followed cells for 10 weeks. First, collaborators in the laboratory of Siddharthan Chandran at the University of Edinburgh collected skin fibroblasts from one person with ALS due to a TDP-43 mutation, two with C9ORF72-based ALS, and three healthy control donors. They turned the fibroblasts into iPS cells and then pushed them toward a motor neuron lineage. Then Devlin took over, spreading the cells on plates to allow the final steps toward a motor neuron fate.

After a couple of weeks, many cells matured to a point where they were electrically active, firing repeated action potentials in response to stimulation. However, the ALS lines shot off more frequent action potentials for a given stimulation than the control lines. β€œThey are definitely more excitable,” Miles concluded.

However, as the cells aged, the percentage of neurons capable of generating action potentials decreased in the ALS lines. By seven weeks, many of those neurons fell silent, mustering no spike at all. This likely explains the conflict between the earlier papers, agreed experts who spoke with Alzforum. β€œ[This paper] gives probably the best evidence to date for the idea of progression from hyperexcitability to reduced excitation,” said Brian Wainger of Massachusetts General Hospital in Charlestown, a member of the group that previously observed hyperexcitability.

Source: ... -crash-als

Re: After seven (7) weeks, hyperexcitability stops in ALS?

PostPosted: February 22nd, 2015, 4:59 am
by joycecaroll
Ok so what does this mean?

Re: After seven (7) weeks, hyperexcitability stops in ALS?

PostPosted: February 22nd, 2015, 7:45 am
by Yuliasir
Joyce, for me the study seems to be not very clear (whether it was designed to prove genetic factor in ALS, or hyperexcitability of the neurons, or something else). Anyway, it seems like there was quite obvious before that so called hyperexcitability stage (which by the way was your obsesssion) lasts not for long and soon is changed for neural silence (due to decomposition of the cells). In other words, nobody usually has hyperexcitability for longer that several weeks in ALS. If a person demonstrates long term hyperexcitability without any neurologicaldeficite, it is neither ALS, nor prerequisite to develop it.

Re: After seven (7) weeks, hyperexcitability stops in ALS?

PostPosted: February 22nd, 2015, 8:25 pm
by Ghayes420
I didn't get much out of this research. Honestly, I don't really care to research ALS. If there is any new developments on fasciculations and their causes, I would be open to reading more on that topic. You may want to stick to researching the same, just a suggestion and opinion.

I did note..."It is hard to say how that weeks-long progression in the dish compares to the decades-long development of ALS in a person, said Robert Baloh of Cedars-Sinai Medical Center in Los Angeles, who saw excitability drop in ALS motor neurons. The events Devlin and others observed might all happen during the development of the human embryo, he speculated. Therefore, researchers cannot be sure how relevant these excitability changes are to human disease. That said, several studies in mouse models and people with ALS back up the idea that excitability goes up or down as the disease progresses (Bories et al., 2007; Kanai et al., 2006; see also Related Papers below)."

I sure hope GM604 continues on the positive path for everyone.