Noise-Induced Hearing Loss Restored in Mice Through Increased NT3 Production

Late to the game here and slightly off topic but did you know they have a monument to these poor fuzzies in Russia?
http://www.neatorama.com/2013/10/07/Monument-to-Lab-Mice-Mouse-Knitting-a-DNA-Strand/

 

When u wrote Russia... Do we have here any member from Russia?
If we do not, does russian medicine have some treatments for t... ex Soviet population (number) is same as USA population... bit strange than here is (if) not members from that region... :/

 

I ordered 0.5 kg 300 euro of this powefull pure stuff to boost nt3 production ..hopefully to fix my tinnitus illegale Let you know

 

I think you may be cured if nerve damage is the cause

 

Ilija Wow we got our t the same way around the same time lol

 

hi

where did you get it? and is it astanxanthin?

 

Check it out: http://hearinghealthfoundation.org/blog?blogid=177

 

Sadly the story is not new by any means. This has been known for a couple of years now but we haven't seen any trials of any kind yet. This is the problem with research at Universities. They don't ever produce anything but papers. They will never trial any drug or anything. The sole purpose is to write a paper and get publicity. If you actually want to make a drug or a therapy of some kind you need a company to that.

 

How did things go with your purchase and use of the product?

 

To continue this thread... I have been taking 12mg of astax daily for about 4 days now. No micro-dropouts for my 4.5 month old noise-induced Tinnitus as of yet as reported by @kramdrol. In fact, no change whatsoever so far. I guess my neurotrophins are stuck in a traffic jam or something...

Maybe I should up the dosage... It's too early to say anything useful anyway. I'll continue taking them for a while...

 

This study is based on the startling discovery a few years back that hair cells are not the most vulnerable element in the inner ear to the effects of noise exposure - the nerve fibers are. If you are exposed to intense levels of noise your outer hair cells will die and your hearing thresholds (the faintest sounds you can hear) will increase. But you can be exposed to more moderate levels of noise that leave your hair cells intact but damage the connection between the auditory nerve and the brain. When these connections are lost, there is no change in thresholds. However, dropping nerve fibers is like losing pixels on your computer display. You can tell whether it is on or off but the more pixels you lose the harder it is to resolve complex images or scenes. Using this analogy, when nerve fibers are lost understanding complex sounds such as speech in a noisy room can become very difficult. The authors of these studies used genetic approach or pharmacology approaches to help damaged nerve fibers reconnect to the hair cells and restore that critical link of cellular communication. There are a few major caveats though - 1) it's in mice, 2) the drug was applied very close to the time of noise exposure. When a lot of time has transpired between the noise exposure and the drug treatment...well, we don't know. But it won't make anything easier. Unfortunately, this is the more common condition for all of us with tinnitus.

 

What's the product called you are taking? I want to give this a shot.

 

Royal Green Astaxanthin. The downside is you have to eat half a bottle to get a considerable dose, as their version is only 4mg per softgel capsule. I'm currently on 20mg, meaning I have to take 5 pieces. This will empty the bottle quite fast. When this is empty I will look for a higher dosage per capsule. I saw a brand named BioAstin selling a version with 12mg per capsule, so that might be better suited.

I have been experiencing a few episodes of intense fleeting Tinnitus just this morning. When it was finally done, it left me with lower/softer Tinnitus. Not sure if this is in any way related to the Astax, but it is a welcome improvement considering my T has been fairly constant and at the same level for a long while.

No side effects, aside from that my burps smell like algae. But hey, if it works I don't care if I smell like a walking sea aquarium.

I will keep taking them for a while (at least a month). In a study of rats with spinal cord injury this appeared to boost NT-3 production (http://www.academicjournals.org/journal/AJPP/article-full-text-pdf/798C13E29545). It appears Astaxanthin is one of the few antioxidants able to cross the blood-brain barrier, which makes it's properties available to the central nervous system. This might be beneficial.

Oh, and supposedly this is of particular interest for people with synapse damage, whether noise-induced or otherwise. I'm not sure if this is supposed to work for the thousands of other etiologies of Tinnitus. Also I'm of course not sure if this will work at all.

 

Ah, I see. I googled it quickly, seems that Now Foods makes a product with 10mg. I'll try to find it locally, and if not, order it online.

 

@Nick Pyzik

I read somewhere that you tried Astaxanthin before. Did it have any effect for you?

I've seen the topic about the retracting spiral ganglion neurons (SGN) and that a softer Tinnitus might actually mean that the SGN is retracting. As Astaxanthin is supposed to boost production of neurotrophin-3 (NT-3), which according to recent research is able to restore or improve connections between the nerve terminals of the SGN and the hair cell (in mice, at least), one would assume this could mean that the Tinnitus would get louder again if the NT-3 is doing it's job. Right? What would be your thoughts on this? Or don't you deem Astaxanthin beneficial at all?

 

Yes, the problem with any kind of treatment always seems to be the time window in which it can be performed. For a lot of us, that time window has been grossly exceeded already. But one thing about this study kept me hopeful; I'm currently at almost 5 months since noise trauma and have seen Charles Liberman mentioning a "window of months to years" for applying treatment on the basis of NT-3, so I'm willing to trial and error by looking for ways to boost NT-3 production. Astaxanthin might be able to do this, as it was mentioned it boosted NT-3 production in mice with spinal cord injury.

I've read however that Charles Liberman is pursuing a targeted treatment by injecting neurotrophins directly to the cochlear round window via intra-tympanic injection. I can imagine a local targeted dose can be much more concentrated and hence effective than what I can ever achieve with any systemic approach. So yes, there are a lot of caveats unfortunately...

I've quoted the excerpt from the Charles Liberman study below for reference regarding the time window.

http://www.ncbi.nlm.nih.gov/pubmed/27108594

 

Vinnitus,

It's hard for me to recall which month I started taking Astaxanthin, but I think it was sometime last December. I purchased a bottle of 12mg Astaxanthin from a local vitamin shoppe after reading about a user on here talking about it. I can remember how desperate I was to see if this would fix my hearing/ringing. Unfortunately, it didn't show any significant results. I was taking it for many months and the only visible changes with taking it was that it gave me more energy and lifted the depressive/Anhedonia issues I'm still dealing with.

I never was actually bothered by my constant ringing last year. It was much more the disconnection I felt from who I was before and the chronic fatigue I was feeling everyday that bothered me. At the time, I was understanding the mechanisms involved in our hearing much more and was much more focused on trying to "feel" emotions again from what I heard. I actually had tried taking "high doses" of vitamin B-12 a few months before I tried Astaxanthin. I can't remember how I found out about B-12 or why I thought it would help the hearing issues/ringing I was having. The best part after taking my first dose of it though was feeling my mood skyrocket. I felt so much better after taking it and raced back after class to what was my "studio setup" at my apartment up at school. I was astounded that I could feel something from the music I was listening to again. But what I was feeling from music after taking b-12 supplements faded after a few weeks. Months later I tried the Astaxanthin. Like I said, it only gave me energy and lifted my somewhat non-existent feelings at the time.

No changes in my ringing around the first months of taking it, but numerous times where "new connections" had to of formed. As many users on TT describe it, my "hearing" went out and came back. I was taking Astxanthin and also a few other ngf supplements like "Lions Mane" and "Ashwaghanda". This happened plenty of times over the past months since last winter. I was having a harder time processing noise for a while until an event where I jammed with a friend. But there are a lot of factors involved as to why I can now hear sound better. I still don't feel anything at all from it.

I have to agree with the study claiming that lower ringing is related to what could be said as "more damage". My ringing has changed so much since last October. It was extremely noticeable at night and also very noticeable in the morning from October to early December. Then as the months rolled by after December, the fan I always have on at night started to block it out. After awhile the ringing started to subdue and so did the rest of my energy, feelings, mood, focus, and a bit of my memories. Or more so something has completely changed with my memories.

I blame the neuronal changes in my hearing for what's going on. It's sadly been so long since I could emotionally enjoy music. So many hidden changes have happened since last fall. There were so many concert that I had ringing after when I was in a band and also when I was going to live concerts. That ringing after was damage. I wish I could understand which spiral ganglion/nerve fiber was involved in the ringing. I know there are two different types, Afferent and Efferent. There are also two different spiral ganglion neurons. Type I and II.

Do you plan on trying Astaxanthin Vinnitus? When did your ringing begin and has it changed at all?

 

Could you point me to this study? Thanks.

 

Yes, the work that Liberman and Corfas have started is intriguing. You are correct that NT-3 was delivered to the cochlear round window (essentially, the back door to the cochlea) in this study but that it could also be delivered through the ear drum (i.e., tympanic membrane) to the oval window. When Liberman mentions "months to years" I believe he is referring to the length of time before the spiral ganglion neuron, the cell that forms the auditory nerve, dies. And yes, that is a good thing (particularly for cochlear implant users). The synapse between the end of the nerve fiber and hair cell is broken immediately after noise exposure. With every day that passes, the end of the nerve terminal retracts further from the hair cell. NT-3 acts like a trail of bread crumbs and can lure the nerve terminal back towards the hair cell, perhaps close enough to restore the synapse and resume communication. Of course, the further the nerve terminal has retracted, the harder it will be to coax it back into position. In their study, if memory serves, they only delivered the NT-3 immediately after the noise exposure, when the nerve terminal would still be in close proximity to its target. So, it remains to be seen whether their cool, encouraging finding holds when the delay between cochlear trauma and NT-3 delivery is longer. Another major hurdle is that NT-3 is a blunt instrument. It could affect the proliferation and connectivity between all kinds of cells in the inner ear, not just the nerve terminal and the inner hair cell. This paper identifies some of the encouraging things that neurotrophin delivery can do. I don't know how much they have investigated its unwanted side effects.

Has this community been keeping up on business news? Do you know about the birth of a new company called Decibel Therapeutics? If not, you might be interested to see their scientific founders - https://decibeltx.com/about-us/founders/

 

That's why I feel like a stem cell based approach to repairing/reconnecting/regenerating the nerve fibers or spiral ganglion neurons would do a lot more justice. There's going to be many subjects who have had ringing for almost decades. I'm assuming it'll all be figured out through trials. If there's ringing, then there still has to be spiral ganglion neurons/nerve fibers alive and resting in between the inner ear and brain. It's so heartbreaking to thing about all the times I had ringing in the past years as it just would go away a few days after. I had no clue how detrimentally hidden all that really was.

Do you think it's actually dangerous to supplement nerve growth factor type herbal/antioxidant type products? I was taking a few for many months, but have ceased taking all of them except for one. Could taking ngf products through digestion actually cause more damage to already inflamed/oxidative stressed neuronal connections in the brain? I ask that last question because my ringing has actually lowered to the point of not being able to hear it very loudly at night or in the morning. I still hear something, but barely. If I've been taking items that protect brain cells/neuronal functions in the brain, then it wouldn't make sense if the damaged neuronal auditory connections actually died? Would it?

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842978/
Quote: "For many years, the dogma in acquired sensorineural hearing loss was that cochlear nerve degeneration only occurred secondarily to hair cell death. Now, we know that if hair cells are destroyed without an external insult, such as noise or ototoxic drugs, cochlear nerve terminals can survive after hair cell loss, so long as supporting cells survive"
End quote.
It is always good to know what is happening in the inner ear, but I wonder if this is good or bad news.
Do we know if it "easier" to repair hair cells or repair synapses?
My gut feeling tells me the synapses are "easier" to fix. But ignorance is bliss.
Quote: "Hair cell counts showed no loss of inner hair cells (Fig. 1G) and moderate (up to 40%) loss of outer hair cells, but only in the basalmost regions of the cochlear spiral of some groups".
End quote: There is still hair cell loss. In the baselmost regions, so that is mid and high frequencies. This is where most people experience hearing loss. So we still need hair cell regeneration.
Wouldn't it be wonderful if this research is an intermediate step to total regeneration

 

Just so I understand, NGF has been helpful in reducing your T?

 

It's hard to say yes or no because so much has gone on since last fall (around early October). I could associate taking supplements/herbs that initiate NGF are actually what caused my ringing to become much louder at times, but it's difficult to say so. There were many other factors that could have played a part. It's just discomforting to not hear as loud ringing or let alone feel anything from my hearing for me because I strongly connect the ringing to auditory nerve damage.

 

It's hard to tell sarcasm through online text, so I'm hoping that's not how it was intended to be. I was intentionally replying back to Vinnitus' statement "I've seen the topic about the retracting spiral ganglion neurons (SGN) and that a softer Tinnitus might actually mean thatthe SGN is retracting."

I do recall someone posting a study on here claiming such. If there wasn't, then I must be going crazy. I'm having difficulty finding the thread though. I'll do some searching though and hopefully pick it out.

 

Perhaps I can be of assistance
http://journal.frontiersin.org/article/10.3389/fneur.2016.00133/full
Quote: "Perhaps the most surprising outcome of the ICc recording experiments was that noise exposure at 100 dB SPL resulted in a greater increase in spontaneous firing rates than did the 105-dB-SPL exposure."
I assume the spontaneous firing rates is our tinnitus?
If not please disregard this post.

 

Hello @Nick Pyzik

Sorry for getting back to you somewhat late.

Your story sounds familiar. I'm also willing to try a lot to restore some of the hearing lost during the concert I visited, or at the very least keep the synapses in a "recoverable state" until some targeted neurotrophin-based treatment comes out.

I am also suffering from Anhedonia, the things which gave me pleasure before my NIHL do not give me pleasure in any way anymore. I used to read a lot, but now I cannot help but think "No, then the ringing will get to me again" and I consequently cancel my plan to do reading. I have to stay busy all the time, as soon as I sit down I will be bothered by it. Doing some work consequently turned from a pleasurable experience into a struggle every day.

If neurotrophin-3 actually does something for the synapses, I would assume the ringing becoming louder while taking it is a good sign, because that might perhaps mean the nerve-terminals stay close to the hair cell they disconnected from. I am however not certain about the correct dosage of Astaxanthin to accomplish this. You said you took 12mg capsules. Did you take just one daily, or multiple? I am currently at 20mg daily. At first it seemed like my Tinnitus got softer, but recently I had some louder episodes again, so I'm not sure either if this stuff is doing anything at all. Taking the systemic approach is probably not the right way to go at it anyway, as I think we need a concentrated high dose on a targeted location in the ear. I wonder what compound would be appropriate for this targeted application...

I also saw you mentioned a fan blocks out your tinnitus while it formerly did not? Do you mean to say your tinnitus improved (got reduced in intensity)? Of course this is both good news and bad news, if the SGN-retraction theory is true.

Regarding my tinnitus; hard to say if it really got better or if it changed at all. It changes a lot, or at least my perception of it. It also changes according to the position of my head. I guess my general opinion is that there really isn't any change, just bad days and slightly better than bad days. Also the ear fullness still goes on after almost 5 months... I read a lot about people saying that the fullness will go away at least, but I don't notice improvement there either. It is particularly annoying because you can "mask" the noise somewhat, but you cannot reduce the feeling of it.

 

I assume the spontaneous firing rates is our tinnitus?

Increased spontaneous rate is a sign that the brain's amplifier is turned up too high. It is not tinnitus, per se. It probably isn't the most informative signature of pathology. It's the easiest one for people measure so it has become popular - probably too poplar - among scientists that study this type of thing.

 

Still surprising than that when damage in the cochlea is greater in this research (after being exposed to a higher sound level) this spontaneous firing is lower than compared with less damage in the cochlea.
If I interpret what I read, correctly.

 

Feeling nothing is pain. I've been told to move on, but there's nothing to move on to. I've felt emotions all my life and now I feel nothing everyday. Plus I've lost all the energy I had before to exercise and what not.

I've taken Astaxanthin since I believe late November. There were times where I took 3-4 more than the recommended amount of (1) 12mg a day. But I've consistently only taken 1 a day including a good few times away from it.

I started using a fan at night because I enjoyed staying cool and because it was soothing before I ever noticed any ringing. This was many years ago. I never have once tried to block out my ringing. I never was annoyed by my ringing, even before I knew what most likely causes the ringing. I'm still puzzled as to why people dislike their ringing. The ringing has to be what allowed them to feel good, feel like themselves, and not be "stressed out". It just doesn't make sense.

It's very difficult for me to remember all the shows I played in my band, but I know I had plenty of ringing after them throughout 2011-13. Even the live concerts I attended. I had ringing after those. I can remember I even had hyperacusis for a very short period of time around 2012. There was hearing change going on 2 years ago and I also had noticeable quiet ringing last summer when in a quiet room. Then I had my two hearing incidents last fall and my hearing has changed all the way to what it's at now.

I'm still taking Astaxanthin to more so help my body and brain push forward. It contains properties that help with oxidative stress and can even protect cell death inside the hippocampus.

My ringing has evolved from very loud, painfully sensitive, and muffled hearing to fine hearing with ringing barely noticeable unless I completely block out every little bit of noise out there. Which I don't think is good at all. "If neurotrophin-3 actually does something for the synapses, I would assume the ringing becoming louder while taking it is a good sign, because that might perhaps mean the nerve-terminals stay close to the hair cell they disconnected from." I agree with that statement. The closer the nerve fiber is to it's associated hair cell, the louder ones ringing will be. It really has got to be that. That's why one will hear very loud ringing after a concert or loud event involving acoustic trauma.

Do you think quite possibly, it's the glutamate that causes the specific nerve fiber to retract back to the spiral ganglion neuron it's associated with and from there the neuron will die unless kept alive by nf? Excess glutamate kills cells. I believe the Peripheral nervous system can repair itself with the help of NGF, so could the brain be sending out nerve fibers from the PNS to take the place of the damaged CNS nerve fibers/spiral ganglion neurons? I really need help understanding if one nerve fiber/spiral ganglion is apart of the CNS and if the other is apart of the PNS? I only understand the basics like which hair cell they attach to or if there is glutamate involved like I said above.