tag:blogger.com,1999:blog-655962722302095847.post1395835722766309681..comments2024-03-28T22:33:35.806+01:00Comments on Epiphany: GABAa receptor trafficking, Migraine, Pain, Light Sensitivity, Autophagy, Jacobsen Syndrome, Angelman Syndrome, GABARAP, TRPV1, PX-RICS, CaMKII and CGRP ... Oh and the "fever effect"Peter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger32125tag:blogger.com,1999:blog-655962722302095847.post-44195149756222565682023-04-05T03:23:30.449+02:002023-04-05T03:23:30.449+02:00about insomnia, do you think melatonin help. i mea...about insomnia, do you think melatonin help. i mean use Kbr and melatonin combineAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-54732012024316503962023-04-04T07:53:48.165+02:002023-04-04T07:53:48.165+02:00Do not use it.Do not use it.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-81740546087454647462023-04-04T07:31:06.728+02:002023-04-04T07:31:06.728+02:00Peter, i bough Kbr from merck and my kid used 2 w...Peter, i bough Kbr from merck and my kid used 2 week. seem not good, he sleeping dificulties and insomnia.sometime he cry without reason. any recommand ?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-52975096929363506652019-10-30T09:22:10.511+01:002019-10-30T09:22:10.511+01:00Tyler, thanks for this.
The pharmaceutical scien...Tyler, thanks for this. <br /><br />The pharmaceutical scientists hoping to develop a new drug for NKCC1, told me that very little is known about the detail of KCC2/NKCC1 and all the isoforms. Any new drug will not be available for very many years, so best to make best use of what we have today. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-81280909927791891352019-10-30T07:12:00.088+01:002019-10-30T07:12:00.088+01:00Thought you (and likely only you) might be interes...Thought you (and likely only you) might be interested in this research on the first three-dimensional structure of KCC1:<br /><br />Press Release:<br /><br />https://www.sciencedaily.com/releases/2019/10/191029092536.htm<br /><br />Paper:<br /><br />https://science.sciencemag.org/content/366/6464/505<br /><br />Of course it is not KCC2, but I thought you might be interested nevertheless.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-24870927059051055652019-10-28T23:34:25.194+01:002019-10-28T23:34:25.194+01:00Well I just came across another bit of research po...Well I just came across another bit of research posted in the last couple of days concerning IL-17A which is a bit of a head scratcher:<br /><br />https://www.spectrumnews.org/news/fevers-immune-effect-on-brain-may-ease-autism-traits/<br /><br />From my look at this, what the researchers are arguing is that maternal immune activation during pregnancy causes a reduction in IL-17A receptors in the somatosensory cortex due to receptor desensitization (and likely other areas of the brain) causing these neurons to be hyperactive after birth as they have a low number of IL-17A receptors. When there is an immune challenge, as opposed to just an artificially induced fever, IL-17A is produced in abundance and this attenuates hyperactive neurons in the somatosensory cortex by strongly and persistently activating the IL-17A receptors. Of course, eventually the receptors will autoregulate back to a preprogrammed state of IL-17A equilibrium (i.e. a tolerance) and so the "fever effect" won't last.<br /><br />I could be reading this wrong as I have yet to read the full paper on the subject as I just came across it, so don't start adding massive amounts of salt to your child's diet to quiet their somatosensory cortex and increase their socialability just yet (-:Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-22415412413506218302019-10-28T17:02:12.996+01:002019-10-28T17:02:12.996+01:00okok will buy it then.okok will buy it then.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-2216335885403172019-10-28T16:28:18.207+01:002019-10-28T16:28:18.207+01:00You will only need one pill to know if it helps. T...You will only need one pill to know if it helps. The effect is that fast. It is worth a try.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-3372536271396241652019-10-28T14:09:41.370+01:002019-10-28T14:09:41.370+01:00Then should I buy the probiotic biogaia protectis ...Then should I buy the probiotic biogaia protectis and take it daily?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-71432972328192823942019-10-28T10:48:50.006+01:002019-10-28T10:48:50.006+01:00Ling, I am not an expert in this field.
Here is a...Ling, I am not an expert in this field.<br /><br />Here is another paper that again includes the role of clustering of GABAa receptors. It also explains the role and interplay of excitatory and inhibitory neurons.<br /><br />Role of GABAAR trafficking in the plasticity of inhibitory synapses<br />https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.13742Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-83630185197935091312019-10-28T10:32:22.768+01:002019-10-28T10:32:22.768+01:00The best person to answer this would be one of our...The best person to answer this would be one of our Aspie readers.<br /><br />One OTC product that may be of benefit is the probiotic Biogaia Protectis usually given to children with stomach problems. It has a secondary effect of increasing the amount of the hormone Oxytocin, which affects emotions. It certainly does this in my son.<br /><br />Oxytocin nasal spray has been used in several autism clinical trials, but the effect does not last long. The bacteria in the probiotic (L. reuteri DSM 17938) continuously produces oxytocin and so could well be better than the nasal spray. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-4173161516164673132019-10-27T22:36:22.192+01:002019-10-27T22:36:22.192+01:00Hi, I've been visiting this site recently as m...Hi, I've been visiting this site recently as my diagnosis is ASD and OCD.. I would like to ask for now if there is there a way to improve my emotional awareness? I mean I almost don't know when I'm not feeling nothing ( Most of my day I don't feel body sensation so I think I can say that I don't feel nothing ) and I don't know if I've inability to feel pleasure.. because I don't even know how pleasure feels like.. what can I do? I'm totally lost... I want to be able to say what I'm feeling on every second of my days.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-62777737774161956832019-10-27T22:13:53.636+01:002019-10-27T22:13:53.636+01:00This comment has been removed by the author.waz1https://www.blogger.com/profile/00842201852253513152noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-48327699336561381112019-10-27T00:23:12.583+02:002019-10-27T00:23:12.583+02:00So CAMKIIa is the kinase that connects NMDA recept...So CAMKIIa is the kinase that connects NMDA receptors, L-type calcium channels and GABAa receptors. Very very cool. Not to forget that CamKII also (up)regulates AMPA receptors and thereby increase synaptic strength.<br /><br />Ok, now I have a number of questions! :-D<br /><br />I had not seen the term "GABAergic iLTP" before. Is it a fancy way of saying "noise reduction" or is there some real link to enhanced LTP/memory that I haven't grasped yet?<br /><br />I would really like to read more on the mechanisms of CaMKII - being so central it deserves a post of its own.<br />Given that CACNA1C is implicated in the susceptibility of all the great neurological diseases it would be nice to get that connection clarified too. If hypertension runs in a family - what does that mean for CaMKII? What happens theoretically if you activate CaMKII more than normal? Is Calmodulin also implicated in autism?<br /><br />Other questions regarding this post:<br />Will bumetanide work if neuronal chloride levels are in range (and the dysfunction is instead in the number of surfacing GABAars?) <br />-Maybe this can be answered by looking at what happens in NT people using Bumetanide, do they get sleepy etc.<br />Is TRPV1 expression modulated by GABARAP independently from GABARAPs function as a GABAar transporter?<br />-That is, is TRPV1 only interesting if your GABARAP for some reason is out of balance, or is it interesting for anyone with activated microglia?<br />Didn't those GABAar also had to be clustered to work perfectly?I vaguely remember an older post on the topic.<br /><br />/LingAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-90909285274377173932019-10-27T00:19:36.685+02:002019-10-27T00:19:36.685+02:00What your paper above says that caught my interest...What your paper above says that caught my interest is that it is not only the Ca2+ current through the NMDAr that activates CaMKII, maybe more important for LTP is that CaMKII is activated by the binding to a specific subunit of the NMDAr. <br />This can't be seen in the graphics of this post, and neither Wikipedia seems knowledgeable of it.<br />Details perhaps, but it also means that just enhancing Ca2+ flow through NMDArs might not be enough to get more LTP/better memory, the available number of NMDA receptors that contain the subunit is also important. <br />Incidentally magnesium, used as a mild memory enhancer, raises the expression of this NMDAr subunit while otherwise being a NMDAr blocker. <br /><br />/LingAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-25262012150760159392019-10-26T19:36:18.782+02:002019-10-26T19:36:18.782+02:00Thanks Michalis, this has not been mentioned. A so...Thanks Michalis, this has not been mentioned. A soak in a hot bath might be a simpler method.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-72871537282028479512019-10-25T22:39:19.860+02:002019-10-25T22:39:19.860+02:00That one looks like a gem. Thank you!
/LingThat one looks like a gem. Thank you!<br /><br />/LingAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-27880280140501688392019-10-25T19:43:49.404+02:002019-10-25T19:43:49.404+02:00I don't know if it has ever been mentioned by ...I don't know if it has ever been mentioned by other readers, but there is a company called avacen medical that is selling a device which raises body temperature by inserting the hand in a heated vacuum chamber. It is FDA cleared for the treatment of arthritis and body pains, but there is also an enrollment for a pilot study for autism called “The Fever Effect: Do kids with autism do better when they use a device to warm their blood? Effects of a six-week AVACEN Treatment Method on Autism Spectrum Disorder”. Michalishttps://www.blogger.com/profile/14576567579569186794noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-58762061813743337972019-10-25T16:39:35.516+02:002019-10-25T16:39:35.516+02:00Very interesting Tyler, I think that if you unders...Very interesting Tyler, I think that if you understand autism you will end up understanding many other disorders from Alzheimer's to MS.<br /><br />It would seem that Agmatine and/or beet juice is wise for autism to raise eNOS and NO. Both are also a good idea to avoid Alzheimer's, at least in research models.<br /><br />Down syndrome features early onset Alzheimer's.<br /><br />Anti-IL17 treatment ameliorates Down syndrome phenotypes in mice<br />https://www.ncbi.nlm.nih.gov/pubmed/29758264 Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-46150259419079353332019-10-25T16:28:14.009+02:002019-10-25T16:28:14.009+02:00Incidentally, sodium bicarbonate (baking soda) is ...Incidentally, sodium bicarbonate (baking soda) is a possible non-salt form of sodium. Also, you coud replace the the chloride in NaCl with KCl.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-28417674892381788472019-10-25T16:16:52.727+02:002019-10-25T16:16:52.727+02:00I just came across some very interesting research ...I just came across some very interesting research concerning the relationship between salt intake and accumulation of the tau protein (Alzheimer's).<br /><br />Press Release:<br /><br />https://www.sciencedaily.com/releases/2019/10/191023132201.htm<br /><br />Paper:<br /><br />https://www.nature.com/articles/s41586-019-1688-z<br /><br />Now what is very interesting with respect to this research is not so much the accumulation of tau via salt intake, but the mechanism of action for this effect to occur. What the researchers essentially found is a link that suggests a high-salt diet leads to the small intestine inducing an inflammatory response which releases copious amounts of Interleukin 17 (IL-17) which then travels to the brain where it reduces blood flow via a reduction in nitric oxide. In other words, you can think of excess salt as being the antithesis of drinking beet juice. This reduction in blood flow is what allows the tau buildup which causes cognitive impairment.<br /><br />Children with autism tend to have elevated levels of IL-17 which could primarily be from any number of other reasons many research papers have already explored in the autism space, but this research linking salt to tau suggests restricting salt in the diet of those with autism who may be sensitive to it (this is just pure speculation on my part), could reduce levels of IL-17 and improve autism symptoms.<br /><br />The issue seems to happen in the gut, so diuretics which waste sodium from the blood likely won't do anything from my reading of all of this as it is an immune response from excess salt that seems to be the problem. It may also be the case that a low-salt or no salt diet could help while the constituents of salt (sodium and chloride) are supplemented back into the diet in forms which do not aggravate this IL-17 immune response.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-12485552298660341842019-10-25T10:33:28.239+02:002019-10-25T10:33:28.239+02:00Carla Marta, I was surprised by that article. Prof...Carla Marta, I was surprised by that article. Prof Hollander a while back replicated the fever effect by placing people in hot tubs, to raise their temperature, so no connection to IL-17, it was just raising their body temperature.<br /><br />I think the fever effect is only genuinely present in a minority of cases.<br /><br />Modifying cytokine expression is actually a very good way to treat autism, but entirely unrelated to the fever effect.<br /><br />Most people feel worse when they are sick, regardless of whether they have autism.<br /><br />As with Dravet syndrome, there will be people whose symptoms get worse as their temperature goes up (regardless of them being ill).<br /><br />It is important not to draw false conclusions.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-74789362133015710842019-10-25T10:24:04.868+02:002019-10-25T10:24:04.868+02:00PE, "patients with tics and OCD had significa...PE, "patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD"<br /><br />Activation/inhibition of CaMKII will have many effects and as stated in the main blog post it is implicated in many neurological disorders.<br /><br />Your paper is relevant to my article. Inhibiting CaMKII might be helpful as a therapeutic intervention. But in conditions like Angelman Syndrome you want the opposite therapy, you want to activate CaMKII.<br /> Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-57316376715203228232019-10-25T10:13:41.363+02:002019-10-25T10:13:41.363+02:00CA, some readers do find a benefit from Resveratro...CA, some readers do find a benefit from Resveratrol and Pterostilbene. If you want a supplement to trial, I would opt for Pterostilbene.<br /><br />In general I think you need drugs to have a major impact on autism.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-49589002045540905742019-10-25T07:05:10.660+02:002019-10-25T07:05:10.660+02:00Is this relevant to this article and Peter can you...Is this relevant to this article and Peter can you give your sense with CamKII: Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics and Obsessive-Compulsive Disorder<br />Conclusion: Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology. Thanks, PE<br />Anonymousnoreply@blogger.com