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Synaptic Plasticity and Signaling Pathways in Neurodevelopmental Disorders (NDDs)

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 1447

Special Issue Editor

Special Issue Information

Dear Colleagues, 

Neurodevelopmental disorders (NDDs) are multifaceted conditions characterized by impairments in cognition, communication, behavior and/or motor skills resulting from abnormal brain development. Intellectual disability, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD) fall under the umbrella of NDD.

Any significant deviation from the normal CNS functions due to social deprivation, environmental factors, genetic and metabolic diseases, and immune disorders results in abnormal neuronal connectivity.

This Special Issue therefore shines light on recent research progress in developmental disorders. Some recent findings which inform the scope of the present Issue are as follows: 

1) Neuroligin 3 (NLGN3) and neurexins (NRXNs) include a canonical transsynaptic cell-adhesion pair in autism spectrum disorder (ASD). Impairment of NLGN3-NRXN interaction shows increased sociability, with imbalance in excitatory/inhibitory synaptic protein expression.

2) Brain-resident innate immune cells (i.e., microglia) have the capacity to sculpt neural circuitry and coordinate copious and diverse neurodevelopmental processes. Components of the innate immune system, including Toll-like receptors, cytokines, inflammasomes and phagocytic signals, are critical contributors to brain development. Dysfunction in innate immune signaling pathways has been functionally linked to many neurodevelopmental disorders.

3) Synaptic alterations of low concentrations of organochlorine pesticides, metabotropic glutamate-receptor-dependent long-term depression (mGluR-LTD) and chronic modulation of MAPK/ERK signaling have been associated with prototypical behavioral phenotypes of MDD. 

4) The available clinical and animal studies evidence links to several common signaling pathways in developmental disorders, including prostaglandin-E2 (PGE2) and cyclooxygenase-2 (COX-2), endocannabinoid (eCB), redox signaling, iron signaling, and copper signaling. Particularly, PGE2 is a membrane-derived lipid signaling molecule and plays an important role in neuronal development associated with canonical Wnt signaling. New synthetic inhibitors of lipolytic enzyme phospholipase A2 (PLA2) may be used for the treatment of neuroinflammation-associated neurodevelopmental disorders in cells. These signaling cascades are involved in various neurodevelopment activities.

Topics of interest include the following:

  • Molecular mechanisms related to the development of neurodevelopment within the central nervous system and medical cues;
  • Neurodevelopment and proteinopathies;
  • New potential biomarkers of developmental disorders during early childhood.

Prof. Dr. Kunio Yui
Guest Editor

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Published Papers (1 paper)

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16 pages, 1094 KiB  
Article
Lipid Peroxidation of the Docosahexaenoic Acid/Arachidonic Acid Ratio Relating to the Social Behaviors of Individuals with Autism Spectrum Disorder: The Relationship with Ferroptosis
by Kunio Yui, George Imataka and Tadashi Shiohama
Int. J. Mol. Sci. 2023, 24(19), 14796; https://doi.org/10.3390/ijms241914796 - 30 Sep 2023
Cited by 1 | Viewed by 1195
Abstract
Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders [...] Read more.
Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders (ASD) and eight age-matched controls. Social behaviors were assessed using the social responsiveness scale (SRS). To overcome the problem of using small samples, adaptive Lasso was used to enhance the interpretability accuracy, and a coefficient of variation was used for variable selections. Plasma levels of the MDA-LDL levels (91.00 ± 16.70 vs. 74.50 ± 18.88) and the DHA/arachidonic acid (ARA) ratio (0.57 ± 0.16 vs. 0.37 ± 0.07) were significantly higher and the superoxide dismutase levels were significantly lower in the ASD group than those in the control group. Total SRS scores in the ASD group were significantly higher than those in the control group. The unbeneficial DHA/ARA ratio induced ferroptosis via lipid peroxidation. Multiple linear regression analysis and adaptive Lasso revealed an association of the DHA/ARA ratio with total SRS scores and increased MDA-LDL levels in plasma, resulting in neuronal deficiencies. This unbeneficial DHA/ARA-ratio-induced ferroptosis contributes to autistic social behaviors and is available for therapy. Full article
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