Jump to content

Menu

Interesting scientific discovery re: neurons and neurotransmitters


wapiti
 Share

Recommended Posts

http://www.medicalnewstoday.com/articles/319033.php (news):

A new study has made the surprising discovery that neurons are capable of controlling how much dopamine they release, which goes against what specialists have hitherto believed. The newly discovered mechanism might hold significant implications for understanding disorders promoted by abnormal dopamine signaling.
 
Neurons are basic structures of the central nervous system, and they communicate with each other using either chemical or electrical signals, some of which are called "neurotransmitters," and these are stored in synaptic vesicles before release. They are finally released by the neurons through "channels" called synapses.
 
Having abnormal levels of two such neurotransmitters, dopamine and glutamate, has previously been linked with various disorders, such as schizophrenia and depression.
 
In a recent study, a team of researchers from the University of Pittsburgh in Pennsylvania have made surprising discoveries about the communication mechanism between neurons. Senior study author Dr. Zachary Freyberg and his colleagues have found that neurons are able to control how much dopamine they release.
 
This goes against what was previously believed about neural communication, and it may hold important implications for treating psychiatric disorders related to neurotransmitter imbalances.
 
"Our findings demonstrate, for the first time, that neurons can change how much dopamine they release as a function of their overall activity. When this mechanism doesn't work properly, it could lead to profound effects on health," says Dr. Freyberg.

 

http://www.cell.com/neuron/fulltext/S0896-6273(17)30686-4?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627317306864%3Fshowall%3Dtrue (journal article)

 

https://www.eurekalert.org/pub_releases/2017-08/uops-rms081617.php (news article):

"Our findings were completely unexpected," said Freyberg. "They contradict the existing dogma that a finite amount of chemical signal is loaded into a vesicle at any given time, and that vesicle acidity is fixed."

 
The team then demonstrated that the increase in acidity was driven by a transport channel in the cell's surface, which allowed an influx of negatively charged glutamate ions to enter the neuron, thus increasing its acidity. Genetically removing the transporter in fruit flies and mice made the animals less responsive to amphetamine, a drug that exerts its effect by stimulating dopamine release from neurons.
 
"In this case, glutamate is not acting as a neurotransmitter. Instead it is functioning primarily as a source of negative charge, which is being used by these vesicles in a really clever way to manipulate vesicle acidity and therefore change their dopamine content," Freyberg said. "This calls into question the whole textbook model of vesicles as having fixed amounts of single neurotransmitters. It appears that these vesicles contain both dopamine and glutamate, and dynamically modify their content to match the conditions of the cell as needed."
  • Like 1
Link to comment
Share on other sites

I haven't quite gotten to it yet, but a certain doc is connecting this to the histamine angle and H3 receptors(?) (which in turn involves the alternate fever response).  It will take me some time to understand what he's trying to say...

 

I was just going to speculate on histamine's role...it makes me wonder if mast cell degranulation influences any of this. It might explain why some people have good luck with dietary and "natural" intervention for various concerns while other people do not.

  • Like 1
Link to comment
Share on other sites

I'm still trying to figure it out myself.  It would seem far more complicated than a glutamate supplement.  All I can say is that for my kiddo, glutamate and dopamine are probably more directly connected to his issues than, say, serotonin.

 

I did happen to come across another interesting newly-published journal article, A Dopamine Hypothesis of Autism Spectrum Disorder

 

The pathogenesis of PANDAS involves molecular mimicry: host antibodies which cross-react with endogenous proteins in the brain, specifically found in the striatum [24]. Autoantibodies from patients with PANDAS were shown to bind to dopaminergic neurons and cause functional alterations. Evidence shows that antibody binding alters the sensitivity of receptors [25], suggesting a role of dopamine signaling anomalies in prompting the behavioral traits in PANDAS. Furthermore, studies show that PANDAS antibodies activate the Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling pathway [26]. CaMKII is a protein kinase involved in various signaling cascades, with key roles in high-order brain functions [27]. In dopaminergic neurons, CaMKII binds directly to D3 dopamine receptor (D3R) and downregulates its function. Given that D3R is preferentially expressed in the striatum, antibody binding could alter reward, motivation, and motor-related behavior in PANDAS patients [28]. Intriguingly, several studies support the role of D3R and CaMKII signaling dysfunctions in ASD [20,21,29,30], indicating a shared pathogenesis between PANDAS and ASD.

 
Altogether, these data suggest that altering dopamine neurotransmission in the striatum might lead to behavioral traits strikingly similar to those of ASD [24]. This provides support for the first prediction yielded by our hypothesis: dopaminergic dysfunctions in the same brain areas associate with autistic-like behavior regardless of diagnosis. Next, we look at the second prediction of our hypothesis, regarding the behavioral improvement in autistic subjects treated with dopamine antagonists.

 

(I hadn't seen that about D3 before, even though I'm very familiar with high CamKII)

 

That article goes on to discuss the role of dopamine antagonists in ASD:

 

The observed therapeutic effect of dopamine antagonists on the autistic core traits is essential in providing support for the second prediction of our hypothesis: if autistic-like behavior arises from dopaminergic dysfunctions, then dopamine modulators should lead to both social and nonsocial behavioral improvement. Blocking dopamine neurotransmission could also prove to be an important therapeutic test, since it leads to behavioral improvement. However, studies are inconsistent and suggest that autistic subjects display general dopaminergic hypoactivity [4,5,6]. Yet, evidence is scarce and contradictory data pose the need for additional studies in order to establish the characteristics of dopamine signaling in ASD. Along these lines, we will further explore ways of testing the dopamine hypothesis of ASD.

 

I wonder whether the contradictory data might be due to the misunderstanding discussed in the OP article about quantities of dopamine released and how that is determined.

 

I'll have to read this over again tomorrow - long day.  I still need to read more on the histamine angle.

Edited by wapiti
Link to comment
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

 Share

×
×
  • Create New...