Neuropeptides In The Neuropsychiatric Disorders Treatment?

[Neonytch]

My name is Igor, I'm a phD student at the Moscow State University. At the moment we are studying the role of natural neuropeptides in the treatment of autism spectrum disorders. I would like to discuss with you the possible positive effects of some neuropeptides on the nervous system.

One of the most interesting classes of peptides is individual neuropeptides that have great potential in the treatment of neuropsychiatric diseases, in particular, some severe forms of autism. Psychotropic drugs of such groups as nootropics, neuroleptics, antidepressants and tranquilizers are traditionally used for the treatment of autism. But pharmacotherapy shows only partial effectiveness in just 25% of cases.

Adrenocorticotropic hormone is a key regulator of the synthesis and release of adrenal hormones. ACTH molecule is composed of 39 amino acid residues. This important hormone is a peptide, and to a greater extent it effect on zona fasciculata, which leads to increased formation of glucocorticoids, to a lesser - on zona glomerulosa and zona reticularis, so it has no significant effect on production of mineralocorticoids and sex hormones. ACTH fragments have a direct impact on the central nervous system and some noteworthy drugs based on them have already developed, in particular, Semax.

Semax relates to a class of regulatory peptides. It is a modified ACTH fragment containing seven amino acid residues. Studies of nootropic activity of the peptide showed that semax improves learning of animals in models both with the positive and negative reinforcement, thus the duration of its effects is not less than 20 hours. He has proven neuroprotective, psychogogic, neuroprotective, anti-oxidative and anti-hypoxic action.

At the moment, we are going to test some modifications on these peptides on valproate model of ASD, in this case we start a science croudfunding project at Experiment croudfunding platform: "Can we fight against autism spectrum disorders using peptide approach?": https://experiment.com/projects/can-we-fight-against-autism-using-peptide-approach .  We are interested in any opinions about our project, which, unfortunately, runs too slowly. So if you have any ideas - I would be grateful. Thank you.

Edited May 12, 2014 by Neonytch

[Ahmabeliever]

Hi Igor, I am pleased to meet you. 

 

My name is Dean, I am currently researching my masters in Autism and the Human Microbiota at Auckland University. I am part of the Minds for Minds network looking at ASD with a multidisciplinary approach. We are looking at genetics, microbiota, urinary and neural metabolites, diet, psychology, histories and much more over a very large (~1000) sample set over time. We (Minds for minds) may be at it for decades if that's what it takes.

 

Did you see the recent small study where 9/10 ASD children showed neural developmental abnormalities in the womb? I am sure this will be expanded on in future too.

 

The concept of neuropeptides is not alien to my project, though not directly involved with such, we suspect a gut-brain-microbiota axis, with two way communication and feedback via various pathways (Cryan & Dinan) and gut microbes make all sorts of interesting compounds themselves including dopamine, seratonin, noradrenaline etc (collectively 150 times the genes of their hosts). So microbes can affect mood and behaviour. Hence some results alleviating symptoms with the right probiotics, or knocking out bacteria to relieve symptoms with antibiotics... There will be metabolites from microbial or host origin that may retard other metabolites causing the changes over time that can make ASD so debilitating. So your idea, to me, has geat merit. It will be interesting to run the genes for your family of peptides through the microbial databases to see if they are there.

 

I imagine collectively over time we'll find better means of identifying the disorder early, and halting or alleviating developmental retardation, and other symptomatic presentation. As for genetic predisposition, with over 300 genes associated with ASD, but all of them with other disorders, and none in more than 1% of the ASD population.... HARD! 

 

I've usually had a wine by the time I'm online, so excuse the strange narrative.

 

I am currently breeding and counting microbes for a mock community to assess the error of several DNA extraction protocol.

[CraigD]

My name is Igor, I'm a phD student at the Moscow State University.

Welcome to hypography, Neonytch/Igor.

 

I’m a medical computer programmer, supporting clinicians in an entirely non-academic, non-research setting, but have enjoyed neuropsychology since my introduction to it in the 1990s, when I wrote software for brain injury rehab under a small team of MDs.

 

With my scant knowledge of pharmacology, much of your post is too technical for me to understand, but I have a few basic questions.

• Do you plan to give neuropeptide-based drugs (such as Semax) during pregnancy, or after?

   

  It seems to me that with the present consensus that ASDs are due to early (first trimester) prenatal development, an effective preventive drug therapy would have to occur.

• Will you be trying your therapy on animals? If so, what animal?

   

  I’m curious how ASDs can be studied in animals, as language problems are one of the primary diagnostic criteria for them in humans, and animals have little language compared to humans.

   

  According to new stories such as this autismspeaks article, suggesting that rather than animals with very well-understood genetics and neuroanatomy/chemistry such as rats, or ones close to humans, such as monkeys and apes, songbirds might be useful for animal studies of ASDs. Are you aware of this work? Could it be useful to you?

• You say “we are going to test some modifications on these peptides on valproate model of ASD”. Can you explain to a non-specialist what valproate models are?

   

  I know that valproate drugs, which are typically used to prevent epileptic seizures, have long been listed as teratogens, so should not be used by women who are pregnant or intend to become pregnant, but know little about studies of how they cause birth defects.

I do not give links for the reason that some moderators consider that I'm spamming, I'm sorry.

Please feel free to post links to your research. As long as what you link to is relevant to the discussion, and you provide comments about the linked-to material in your post, we won’t consider it spam. See our site rules for more details.

[Turtle]

My name is Igor, I'm a phD student at the Moscow State University. At the moment we are studying the role of natural neuropeptides in the treatment of autism spectrum disorders. I would like to discuss with you the possible positive effects of some neuropeptides on the nervous system. ...

Hi Igor,

 

I'm curious to know if autism is as prevalent in Russia as it is in the US. Thanks.

[Neonytch]

With my scant knowledge of pharmacology, much of your post is too technical for me to understand, but I have a few basic questions.

• Do you plan to give neuropeptide-based drugs (such as Semax) during pregnancy, or after?

 

After pregnancy, the mechanisms of action of these peptides during pregnancy requires further studys. Direct intranasal administration is much more easier and clear.

 

2. Will you be trying your therapy on animals? If so, what animal?

 

I’m curious how ASDs can be studied in animals, as language problems are one of the primary diagnostic criteria for them in humans, and animals have little language compared to humans.

 

Rodent models of ASD are widely used in studies, you can read about them here (with more details about VPA-model too):

 

http://www.researchgate.net/publication/222678633_Rodent_models_for_autism_A_critical_review

http://www.sciencedirect.com/science/article/pii/S0166432813003264

http://www.sciencedirect.com/science/article/pii/S0889159112002188

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513683/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414062/

 

What about our model, it is quite interesting, precisely because of the effect on the nervous system of the offspring. Valproate model of ASD is performed by prenatal administration of high doses of valproic acid (VPA) to female rat on 12th day of pregnancy. The following characteristics (similar to ASD) were observed in behavior of cubs with fetal valproate syndrome: disturbances in nociception and locomotion;stereotyped hyperactivity in combination with low motivation to explore; increased level of anxiety; low repertoire of social behavior components in combination with increased latency of social behavior. So, we hope to get intresting results with this model.

 

 

Hi Igor, I am pleased to meet you. 

 

My name is Dean, I am currently researching my masters in Autism and the Human Microbiota at Auckland University. I am part of the Minds for Minds network looking at ASD with a multidisciplinary approach. We are looking at genetics, microbiota, urinary and neural metabolites, diet, psychology, histories and much more over a very large (~1000) sample set over time. We (Minds for minds) may be at it for decades if that's what it takes.

 

Did you see the recent small study where 9/10 ASD children showed neural developmental abnormalities in the womb? I am sure this will be expanded on in future too.

 

The concept of neuropeptides is not alien to my project, though not directly involved with such, we suspect a gut-brain-microbiota axis, with two way communication and feedback via various pathways (Cryan & Dinan) and gut microbes make all sorts of interesting compounds themselves including dopamine, seratonin, noradrenaline etc (collectively 150 times the genes of their hosts). So microbes can affect mood and behaviour. Hence some results alleviating symptoms with the right probiotics, or knocking out bacteria to relieve symptoms with antibiotics... There will be metabolites from microbial or host origin that may retard other metabolites causing the changes over time that can make ASD so debilitating. So your idea, to me, has geat merit. It will be interesting to run the genes for your family of peptides through the microbial databases to see if they are there.

 

I imagine collectively over time we'll find better means of identifying the disorder early, and halting or alleviating developmental retardation, and other symptomatic presentation. As for genetic predisposition, with over 300 genes associated with ASD, but all of them with other disorders, and none in more than 1% of the ASD population.... HARD! 

 

I've usually had a wine by the time I'm online, so excuse the strange narrative.

 

I am currently breeding and counting microbes for a mock community to assess the error of several DNA extraction protocol.

 

Wow, you have a great and exciting project, our research area is much narrower.

[Ahmabeliever]

It is good being part of a larger project, but am stuck in a microbe lab mostly. You are very welcome to join minds for minds. https://www.arnnz.org/

 

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I enjoyed the rodent papers, thank you.

[TexasSkye1]

Igor, what was the result of your study?

[write4u]

I  am merely an interested bystander and I cannot contribute to the science,  but from reading I found an interesting connection between autism and microtubule fnction.  I don't know if this is pertinent to the discussion, but thought it might be of interest .  This will be my only post  and I'll sit back and learn.

Role of Microtubule-Associated Protein in Autism Spectrum Disorder

Abstract

 

Quote

 

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with repetitive and restrictive patterns of behaviors or interests. Normal brain development is crucial to behavior and cognition in adulthood. Abnormal brain development, such as synaptic and myelin dysfunction, is involved in the pathogenesis of ASD. Microtubules and microtubule-associated proteins (MAPs) are important in regulating the processes of brain development, including neuron production and synaptic formation, as well as myelination. Increasing evidence suggests that the level of MAPs are changed in autistic patients and mouse models of ASD. Here, we discuss the roles of MAPs.

Keywords: Autism spectrum disorder, Microtubule-associated proteins, Synapse, Myelin

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246838/#

[write4u]

One more post hoping for a response..

Abstract

Quote

Somatostatin (SST) is a growth hormone inhibitory peptide involved in regulation of several physiological responses of cells including neurotransmission, cell migration, maturation, and neurite formation. In the present study, we examined the role of SST in all-trans retinoic acid (RA)-induced progression of neurite outgrowth in SH-SY5Y cells. We also determined the morphological and developmental changes in prominent intracellular markers of neurite growth including microtubule-associated protein 2 (MAP2), neuron-specific III β-tubulin (TUJ1), and Tau. Here, we present evidence that SST is a molecular determinant in regulating the transition of SH-SY5Y cells from non-neuronal entity to neuronal phenotype in response to RA. The results from present study reveal that SST changes the distributional pattern of MAP2/Tau and TUJ1, and activates extracellular signal-regulated kinase (ERK1/2) signaling pathway through SST receptors (SSTRs). The expression of MAP2 and Tau remains elevated upon treatment with RA and SST alone or in combination. Importantly, we identified that the cells displaying strong co-expression of SST and TUJ1 are more likely to bear elongated neurite formation than cells devoid of such expression. These findings show that the site-specific expression of MAP2 and TUJ1 is an essential determinant of neurite outgrowth in SH-SY5Y cells in RA-mediated differentiation. Taken together, results presented here further substantiates the role of SST in the promotion of neurite formation and elongation in SH-SY5Y cells in combination with RA. Investigating how SST can improve neurite formation in neurodegenerative disease may help to develop new therapeutic approach in improving cognitive function and memory loss.

 https://pubmed.ncbi.nlm.nih.gov/30879180/