Chronic Tinnitus and Unipolar Brush Cell Alterations in the Cerebellum and Dorsal Cochlear Nucleus

[NatureHiker]

Highlights
• Unipolar brush cells (UBC) may serve as a cellular substrate of chronic tinnitus.
• Tinnitus elevated a synaptic remodeling indicator, Eps8, in cerebellar UBCs.
• Eps8 was not elevated, but decreased, in UBCs of non-tinnitus rats.
• Synaptic remodeling in a UBC gain-modulation circuit could underpin chronic tinnitus.
• Sound exposure caused neural degeneration, but was not exclusive to tinnitus.

Abstract
Animal model research has shown that the central features of tinnitus, the perception of sound without an acoustic correlate, include elevated spontaneous and stimulus-driven activity, enhanced burst-mode firing, decreased variance of inter-spike intervals, and distortion of tonotopic frequency representation. Less well documented are cell-specific correlates of tinnitus. Unipolar brush cell (UBC) alterations in animals with psychophysical evidence of tinnitus has recently been reported. UBCs are glutamatergic interneurons that appear to function as local-circuit signal amplifiers. UBCs are abundant in the dorsal cochlear nucleus (DCN) and very abundant in the flocculus (FL) and paraflocculus (PFL) of the cerebellum. In the present research, two indicators of UBC structure and function were examined: Doublecortin (DCX) and epidermal growth factor receptor substrate 8 (Eps8). DCX is a protein that binds to microtubules where it can modify their assembly and growth. Eps8 is a cell-surface tyrosine kinase receptor mediating the response to epidermal growth factor; it appears to have a role in actin polymerization as well as cytoskeletal protein interactions. Both functions could contribute to synaptic remodeling. In the present research UBC Eps8 and DCX immunoreactivity (IR) were determined in 4 groups of rats distinguished by their exposure to high-level sound and psychophysical performance: Unexposed, exposed to high-level sound with behavioral evidence of tinnitus, and two exposed groups without behavioral evidence of tinnitus. Compared to unexposed controls, exposed animals with tinnitus had Eps8 IR elevated in their PFL; other structures were not affected, nor was DCX IR affected. This was interpreted as UBC upregulation in animals with tinnitus. Exposure that failed to produce tinnitus did not increase either Eps8 or DCX IR. Rather Eps8 IR was decreased in the FL and DCN of one subgroup (Least-Tinnitus), while DCX IR decreased in the FL of the other subgroup (No-Tinnitus). Neuron degeneration was also documented in the cochlear nucleus and PFL of exposed animals, both with and without tinnitus. Degeneration was not found in unexposed animals. Implications for tinnitus neuropathy are discussed in the context of synaptic remodeling and cerebellar sensory modulation.

http://www.sciencedirect.com/science/article/pii/S037859551730059X#

 

[Dr. Jay Hobbs]

Pretty heavy read there @NatureHiker .
I categorize this finding in with predisposing factors, what I call the (Un)Healthy Brain Lifestyle. It may be inflammation, immune reactivity, etc., but what predisposes one over another, if you address that factor(s), you improve the recovery and reduce the maladaption.
For a rat example,
Protective Effect of Nigella Sativa Oil (cumin) on Acoustic Trauma Induced Hearing Loss in Rats. (Audiol Res. 2017 Jul 18;7(2):181. ), and a series of case studies in humans:

1. Konopka W, Zalewski P, Olszewski J, Olszewska-Ziaber A, Pietkiewicz P. Treatment results of acoustic trauma. Otolaryngol Pol. 1997;51 Suppl 25:281-4.

I see this as potentially a great intervention right after acoustic trauma, as with soldiers, to reduce hearing loss and Tinnitus development.

 

[HomeoHebbian]

Pretty heavy read there @NatureHiker .
I categorize this finding in with predisposing factors, what I call the (Un)Healthy Brain Lifestyle. It may be inflammation, immune reactivity, etc., but what predisposes one over another, if you address that factor(s), you improve the recovery and reduce the maladaption.
For a rat example,
Protective Effect of Nigella Sativa Oil (cumin) on Acoustic Trauma Induced Hearing Loss in Rats. (Audiol Res. 2017 Jul 18;7(2):181. ), and a series of case studies in humans:

1. Konopka W, Zalewski P, Olszewski J, Olszewska-Ziaber A, Pietkiewicz P. Treatment results of acoustic trauma. Otolaryngol Pol. 1997;51 Suppl 25:281-4.

I see this as potentially a great intervention right after acoustic trauma, as with soldiers, to reduce hearing loss and Tinnitus development.

That utterly and completely misses the point of this article, doc. They are describing a structural signature for a potential key neuronal regulator of tinnitus perception. This cell type (UBCs) are positioned to play a key role in amplifying activity within the central authority pathway and this study identifies an enriched protein found only in the subset of noise exposed rats that show behavioral changes that may be related to tinnitus. What this has to do with snake oil - sorry, cumin oil, is escaping me.

 

[stophiss]

That utterly and completely misses the point of this article, doc. They are describing a structural signature for a potential key neuronal regulator of tinnitus perception. This cell type (UBCs) are positioned to play a key role in amplifying activity within the central authority pathway and this study identifies an enriched protein found only in the subset of noise exposed rats that show behavioral changes that may be related to tinnitus. What this has to do with snake oil - sorry, cumin oil, is escaping me.

Can you elaborate on what you mean about having to do with snake oil? You seem to be obtusely relating snake oil to pre-disposition. Are you saying the findings are credible and applicable to possible cure or abatement of tinnitus and somewhat unrelated to the doc's assertion about predisposition? Even with predisposition, are you saying this article is important and that pre-disposition isn't at least overarching because it can be reversed? Of course all of us with tinnitus predisposed by heredity and environment...two overwhelming causal factors... are hoping for a treatment that can reduce tinnitus.

Please expand your thoughts if you would.

 

[HomeoHebbian]

Can you elaborate on what you mean about having to do with snake oil? You seem to be obtusely relating snake oil to pre-disposition. Are you saying the findings are credible and applicable to possible cure or abatement of tinnitus and somewhat unrelated to the doc's assertion about predisposition? Even with predisposition, are you saying this article is important and that pre-disposition isn't at least overarching because it can be reversed? Of course all of us with tinnitus predisposed by heredity and environment...two overwhelming causal factors... are hoping for a treatment that can reduce tinnitus.

Please expand your thoughts if you would.

Snake oil is another way of saying a bogus therapy. I find it frustrating when people who use "Dr" in their title, waltz into a discussion in this excellent forum and write something totally unrelated to the topic of the thread and instead start plugging bogus science on an unrelated theme. This thread could focus on unipolar brush cells: What are they? Why are they a potential master regulator of tinnitus?

When an "expert" writes something pedantic and then references two studies that are unrelated to the topic of the thread - one an old study from an obscure journal with a deeply flawed experimental design, the other a study in rats that did not address tinnitus - it really ticks me off because it devalues what the research forum is trying to do. I think hyping crappy studies with poor scientific foundations belongs on other parts of this web forum.

 

[stophiss]

Snake oil is another way of saying a bogus therapy. I find it frustrating when people who use "Dr" in their title, waltz into a discussion in this excellent forum and write something totally unrelated to the topic of the thread and instead start plugging bogus science on an unrelated theme. This thread could focus on unipolar brush cells: What are they? Why are they a potential master regulator of tinnitus?

When an "expert" writes something pedantic and then references two studies that are unrelated to the topic of the thread - one an old study from an obscure journal with a deeply flawed experimental design, the other a study in rats that did not address tinnitus - it really ticks me off because it devalues what the research forum is trying to do. I think hyping crappy studies with poor scientific foundations belongs on other parts of this web forum.

Now I will state my view. I find your criticism course and crude. I am a scientist FWIW and I understand technical discourse. Your snake oil reference was banal and obtuse. What you didn't go on to say is why the Dr. is wrong other than your generic and scathing repudiation that 'he was wrong.'

The Dr. in question for example may not be an expert in tinnitus however takes an interest in it. He proffered his opinion...technically based or not, and you sully the forum by attacking him and not even providing a substantive technical rebuttal to why he is wrong.

So if 'you' have any validity, why don't you try again without attacking somebody on this forum? If you dismiss UBC related therapy then explain why. If you support this therapy then explain why and why you believe the Dr. is in error.

Calling something snake oil without explaining the basis for this put down is a cope out.

 

[HomeoHebbian]

Now I will state my view. I find your criticism course and crude. I am a scientist FWIW and I understand technical discourse. Your snake oil reference was banal and obtuse. What you didn't go on to say is why the Dr. is wrong other than your generic and scathing repudiation that 'he was wrong.'

The Dr. in question for example may not be an expert in tinnitus however takes an interest in it. He proffered his opinion...technically based or not, and you sully the forum by attacking him and not even providing a substantive technical rebuttal to why he is wrong.

So if 'you' have any validity, why don't you try again without attacking somebody on this forum? If you dismiss UBC related therapy then explain why. If you support this therapy then explain why and why you believe the Dr. is in error.

Calling something snake oil without explaining the basis for this put down is a cope out.

Cumin oil and unipolar brush cells have NOTHING to do with one another. I'm suggesting that discussions about unipolar brush cells are interesting and worthwhile. Take it easy...

 

[stophiss]

Cumin oil and unipolar brush cells have NOTHING to do with one another. I'm suggesting that discussions about unipolar brush cells are interesting and worthwhile. Take it easy...

A bit more clear now. Your snake oil reference was a dissing of cumin oil which you feel is unrelated to UBC.

My point, is the Dr. could have screwed up with his post. They are seemingly unrelated I agree. I don't know his background. I guess we will see if he responds. If he doesn't you win.