scholarly journals L1-79 and the Role of Catecholamines in Autism

2020 ◽  
Author(s):  
John Rothman

A growing body of evidence supports a role for catecholaminergic dysfunction in the core symptoms of autism spectrum disorder (ASD). This paper reviews the direct and indirect role of catecholamines on the central and peripheral nervous systems in ASD. Catecholamines innervate every tissue in the body and almost all tracts of the brain, providing a common neurologic regulatory mechanism for all ASD symptoms. Because the morphology of the catecholaminergic synapse is regulated by growth factors that are released contemporaneously with neurotransmitters, an event that results in abnormally large catecholamine release, will also release high levels of growth factors, which can result in the budding and arborization of nerve terminals. Here, we hypothesize that a hypertrophic synaptic morphology can occur in catecholaminergic systems and increase catecholaminergic tone throughout the body, resulting in an imbalance between catecholaminergic neurologic mechanisms and those that oppose them, and consequently pathology. By exerting a presynaptic effect to inhibit tyrosine hydroxylase and thus the synthesis, storage and release of all catecholamines, L1–79 (a tyrosine hydroxylase inhibitor) may diminish neurotransmitter release and its associated growth factors exerting a therapeutic effect on ASD by reducing the hypertrophic morphology of the synapse and bringing catecholamines back into a homeostatic balance with oppositional neurologic and metabolic influences.


2017 ◽  
Vol 76 (4) ◽  
pp. 478-483
Author(s):  
Paul Whiteley

Complex, diverse and rarely appearing without comorbidity, the autism spectrum disorders continue to be a source of research interest. With core symptoms variably impacting on social communication skills, the traditional focus of many research efforts has centred on the brain and how genetic and environmental processes impact on brain structure, function and/or connectivity to account for various behavioural presentations. Alongside emerging ideas on autistic traits being present in various clinical states, the autisms, and the overrepresentation of several comorbid conditions impacting on quality of life, other research avenues have opened up. The central role of the brain in relation to autism may be at least partially influenced by the functions of other organs. The gastrointestinal (GI) tract represents an important biological system pertinent to at least some autism. The notion of a gut–brain–behaviour axis has garnered support from various findings: an overrepresentation of functional and pathological bowel states, bowel and behavioural findings showing bidirectional associations, a possible relationship between diet, GI function and autism and recently, greater focus on aspects of the GI tract such as the collected gut microbiota in relation to autism. Gaps remain in our knowledge of the functions of the GI tract linked to autism, specifically regarding mechanisms of action onward to behavioural presentation. Set however within the context of diversity in the presentation of autism, science appears to be moving towards defining important GI-related autism phenotypes with the possibility of promising dietary and other related intervention options onward to improving quality of life.



2020 ◽  
Vol 8 (8) ◽  
pp. 4245-4249
Author(s):  
Pranita Milind Deshpande ◽  
Anil Managuli

Skin is a type of Gyanendriya (Sparshna indriya) and largest sense organ in the body. It is result of healthy constitution of body as well as healthy mental state. Skin has great cosmetological importance. Due to sed-entary lifestyle, inappropriate diet habits and excessive stress, numerous skin aliments arise. Hence it is need for inculcating healthy skin care habits. One of the common worrying factors related to skin is Dark circles. It affects almost all age groups and is most commonly related to stress and anxiety. Drugs adminis-tered through nasal route acts on higher centers of the brain. It acts on neurological, endocrinal and circula-tory centers and regulates their functions. This study is aimed to evaluate the role of Nasya Karma with kumkumadi taila in Dark circles.



2020 ◽  
Author(s):  
Jason He ◽  
Ericka Wodka ◽  
Mark Tommerdahl ◽  
Richard Edden ◽  
Mark Mikkelsen ◽  
...  

Alterations of tactile processing have long been identified in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the extent to which these alterations are disorder-specific, rather than disorder-general, and how they relate to the core symptoms of each disorder, remains unclear. We measured and compared tactile detection, discrimination and order judgment thresholds between a large sample of children with ASD, ADHD, ASD + ADHD combined and typically developing controls. The pattern of results suggested that while difficulties with tactile detection and order judgement were more common in children with ADHD, difficulties with tactile discrimination were more common in children with ASD. Strikingly, subsequent correlation analyses found that the disorder-specific alterations suggested by the group comparisons were also exclusively related to the core symptoms of each respective disorder. These results suggest that disorder-specific alterations of lower-level sensory processes exist and are specifically related to higher-level clinical symptoms of each disorder.



2020 ◽  
Vol 26 ◽  
Author(s):  
Cristian Muresanu ◽  
Siva G. Somasundaram ◽  
Sergey V. Vissarionov ◽  
Liliya V. Gavryushova ◽  
Vladimir N. Nikolenko ◽  
...  

Background: From the evidence of failed injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. Objective: We seek to stimulate discussions and more research about the possibility of using the already available growth factors found in the prostate gland and endometrium by starting a novel educable physiology, known as biological transformations controlled by the mind. Methods: We summarized the stretch-gated ion channel mechanism of the cell membrane, and offer several practical methods that can be applied by anyone, in order to stimulate and enhance the blood circulation of the growth factors from the seminal fluid to sites throughout the body. This details the practical application of our earlier published studies about biological transformations. Results: A previously reported single-patient case study has been extended, adding more from his personal experiences continually improving this novel physiological training and extending the ideas from our earlier findings in detail. Conclusion: The biological transformation findings demonstrate the need additional research to establish the benefits of these natural therapies to repair and rejuvenate tissues affected by various chronic diseases or aging processes.



2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Reymundo Lozano ◽  
Catherine Gbekie ◽  
Paige M. Siper ◽  
Shubhika Srivastava ◽  
Jeffrey M. Saland ◽  
...  

AbstractFOXP1 syndrome is a neurodevelopmental disorder caused by mutations or deletions that disrupt the forkhead box protein 1 (FOXP1) gene, which encodes a transcription factor important for the early development of many organ systems, including the brain. Numerous clinical studies have elucidated the role of FOXP1 in neurodevelopment and have characterized a phenotype. FOXP1 syndrome is associated with intellectual disability, language deficits, autism spectrum disorder, hypotonia, and congenital anomalies, including mild dysmorphic features, and brain, cardiac, and urogenital abnormalities. Here, we present a review of human studies summarizing the clinical features of individuals with FOXP1 syndrome and enlist a multidisciplinary group of clinicians (pediatrics, genetics, psychiatry, neurology, cardiology, endocrinology, nephrology, and psychology) to provide recommendations for the assessment of FOXP1 syndrome.



2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.



2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.



Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.



2018 ◽  
Vol 17 (4) ◽  
pp. 281-286 ◽  
Author(s):  
Olga V. Kostina

The review presents an analysis of the mechanisms of iron effect on the brain development. The importance of iron deficiency in the perinatal period is considered as a risk factor for the development of neuropsychiatric disorders in children with autism spectrum disorders (ASDs). Possible causes of sideropenia are discussed; data on haematological and biochemical parameters characterizing iron metabolism in children with ASDs are presented. The demand for studying the role of iron metabolism imbalance in the development of neuropsychiatric disorders in order to clarify pathogenetic mechanisms of ASDs and to determine methods for their correction is emphasized.



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