Proteomic Analysis of Brain Region and Sex-Specific Synaptic Protein Expression in the Adult Mouse Brain

Genetic disruption of synaptic proteins results in a whole variety of human neuropsychiatric disorders including intellectual disability, schizophrenia or autism spectrum disorder (ASD). In a wide range of these so-called synaptopathies a sex bias in prevalence and clinical course has been reported. Using an unbiased proteomic approach, we analyzed the proteome at the interaction site of the pre- and postsynaptic compartment, in the prefrontal cortex, hippocampus, striatum and cerebellum of male and female adult C57BL/6J mice. We were able to reveal a specific repertoire of synaptic proteins in different brain areas as it has been implied before. Additionally, we found a region-specific set of novel synaptic proteins differentially expressed between male and female individuals including the strong ASD candidates DDX3X, KMT2C, MYH10 and SET. Being the first comprehensive analysis of brain region-specific synaptic proteomes from male and female mice, our study provides crucial information on sex-specific differences in the molecular anatomy of the synapse. Our efforts should serve as a neurobiological framework to better understand the influence of sex on synapse biology in both health and disease.

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Prenatal Exposure to Valproic Acid Affects Microglia and Synaptic Ultrastructure in a Brain-Region-Specific Manner in Young-Adult Male Rats: Relevance to Autism Spectrum Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms21103576 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3576 ◽

Cited By ~ 3

Author(s):

Magdalena Gąssowska-Dobrowolska ◽

Magdalena Cieślik ◽

Grzegorz Arkadiusz Czapski ◽

Henryk Jęśko ◽

Małgorzata Frontczak-Baniewicz ◽

...

Keyword(s):

Valproic Acid ◽

Autism Spectrum Disorders ◽

Young Adult ◽

Prenatal Exposure ◽

Adult Male ◽

Brain Region ◽

Autism Spectrum ◽

Synaptic Proteins ◽

Specific Manner ◽

Spectrum Disorders

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions categorized as synaptopathies. Environmental risk factors contribute to ASD aetiology. In particular, prenatal exposure to the anti-epileptic drug valproic acid (VPA) may increase the risk of autism. In the present study, we investigated the effect of prenatal exposure to VPA on the synaptic morphology and expression of key synaptic proteins in the hippocampus and cerebral cortex of young-adult male offspring. To characterize the VPA-induced autism model, behavioural outcomes, microglia-related neuroinflammation, and oxidative stress were analysed. Our data showed that prenatal exposure to VPA impaired communication in neonatal rats, reduced their exploratory activity, and led to anxiety-like and repetitive behaviours in the young-adult animals. VPA-induced pathological alterations in the ultrastructures of synapses accompanied by deregulation of key pre- and postsynaptic structural and functional proteins. Moreover, VPA exposure altered the redox status and expression of proinflammatory genes in a brain region-specific manner. The disruption of synaptic structure and plasticity may be the primary insult responsible for autism-related behaviour in the offspring. The vulnerability of specific synaptic proteins to the epigenetic effects of VPA may highlight the potential mechanisms by which prenatal VPA exposure generates behavioural changes.

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Developing Equations for Converting Digestible Energy to Metabolizable Energy for Korean Hanwoo Beef Cattle

Animals ◽

10.3390/ani11061696 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1696

Author(s):

Ridha Ibidhi ◽

Rajaraman Bharanidharan ◽

Jong-Geun Kim ◽

Woo-Hyeong Hong ◽

In-Sik Nam ◽

...

Keyword(s):

Linear Regression ◽

Beef Cattle ◽

Strong Relationship ◽

Dietary Factors ◽

Metabolizable Energy ◽

Coefficient Of Determination ◽

Simple Linear Regression ◽

Male And Female ◽

Digestible Energy ◽

Wide Range

This study was performed to update and generate prediction equations for converting digestible energy (DE) to metabolizable energy (ME) for Korean Hanwoo beef cattle, taking into consideration the gender (male and female) and body weights (BW above and below 350 kg) of the animals. The data consisted of 141 measurements from respiratory chambers with a wide range of diets and energy intake levels. A simple linear regression of the overall unadjusted data suggested a strong relationship between the DE and ME (Mcal/kg DM): ME = 0.8722 × DE + 0.0016 (coefficient of determination (R2) = 0.946, root mean square error (RMSE) = 0.107, p < 0.001 for intercept and slope). Mixed-model regression analyses to adjust for the effects of the experiment from which the data were obtained similarly showed a strong linear relationship between the DE and ME (Mcal/kg of DM): ME = 0.9215 × DE − 0.1434 (R2 = 0.999, RMSE = 0.004, p < 0.001 for the intercept and slope). The DE was strongly related to the ME for both genders: ME = 0.8621 × DE + 0.0808 (R2 = 0.9600, RMSE = 0.083, p < 0.001 for the intercept and slope) and ME = 0.7785 × DE + 0.1546 (R2 = 0.971, RMSE = 0.070, p < 0.001 for the intercept and slope) for male and female Hanwoo cattle, respectively. By BW, the simple linear regression similarly showed a strong relationship between the DE and ME for Hanwoo above and below 350 kg BW: ME = 0.9833 × DE − 0.2760 (R2 = 0.991, RMSE = 0.055, p < 0.001 for the intercept and slope) and ME = 0.72975 × DE + 0.38744 (R2 = 0.913, RMSE = 0.100, p < 0.001 for the intercept and slope), respectively. A multiple regression using the DE and dietary factors as independent variables did not improve the accuracy of the ME prediction (ME = 1.149 × DE − 0.045 × crude protein + 0.011 × neutral detergent fibre − 0.027 × acid detergent fibre + 0.683).

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Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms22147281 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7281

Author(s):

Benoit R. Gauthier ◽

Valentine Comaills

Keyword(s):

Nuclear Envelope ◽

Clinical Symptoms ◽

Genome Instability ◽

Chromosomal Rearrangements ◽

Wide Range ◽

Complex Chromosomal Rearrangements ◽

Health And Disease ◽

Dna Release ◽

Sting Pathway ◽

Eukaryote Genome

The dynamic nature of the nuclear envelope (NE) is often underestimated. The NE protects, regulates, and organizes the eukaryote genome and adapts to epigenetic changes and to its environment. The NE morphology is characterized by a wide range of diversity and abnormality such as invagination and blebbing, and it is a diagnostic factor for pathologies such as cancer. Recently, the micronuclei, a small nucleus that contains a full chromosome or a fragment thereof, has gained much attention. The NE of micronuclei is prone to collapse, leading to DNA release into the cytoplasm with consequences ranging from the activation of the cGAS/STING pathway, an innate immune response, to the creation of chromosomal instability. The discovery of those mechanisms has revolutionized the understanding of some inflammation-related diseases and the origin of complex chromosomal rearrangements, as observed during the initiation of tumorigenesis. Herein, we will highlight the complexity of the NE biology and discuss the clinical symptoms observed in NE-related diseases. The interplay between innate immunity, genomic instability, and nuclear envelope leakage could be a major focus in future years to explain a wide range of diseases and could lead to new classes of therapeutics.

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Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder

International Journal of Molecular Sciences ◽

10.3390/ijms22062811 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2811

Author(s):

Yuyoung Joo ◽

David R. Benavides

Keyword(s):

Autism Spectrum Disorder ◽

Fragile X ◽

Single Gene ◽

Protein Translation ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Spectrum Disorder ◽

Synaptic Proteins ◽

Local Translation ◽

Translation Control

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.

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The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population

Molecular Autism ◽

10.1186/s13229-021-00445-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Michael C. W. English ◽

Gilles E. Gignac ◽

Troy A. W. Visser ◽

Andrew J. O. Whitehouse ◽

James T. Enns ◽

...

Keyword(s):

Factor Analysis ◽

General Population ◽

Measurement Invariance ◽

High Reliability ◽

Predictive Ability ◽

Autistic Traits ◽

Autism Spectrum ◽

Autism Spectrum Quotient ◽

Sensory Sensitivity ◽

Wide Range

Abstract Background Traits and characteristics qualitatively similar to those seen in diagnosed autism spectrum disorder can be found to varying degrees in the general population. To measure these traits and facilitate their use in autism research, several questionnaires have been developed that provide broad measures of autistic traits [e.g. Autism-Spectrum Quotient (AQ), Broad Autism Phenotype Questionnaire (BAPQ)]. However, since their development, our understanding of autism has grown considerably, and it is arguable that existing measures do not provide an ideal representation of the trait dimensions currently associated with autism. Our aim was to create a new measure of autistic traits that reflects our current understanding of autism, the Comprehensive Autism Trait Inventory (CATI). Methods In Study 1, 107 pilot items were administered to 1119 individuals in the general population and exploratory factor analysis of responses used to create the 42-item CATI comprising six subscales: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. In Study 2, the CATI was administered to 1068 new individuals and confirmatory factor analysis used to verify the factor structure. The AQ and BAPQ were administered to validate the CATI, and additional autistic participants were recruited to compare the predictive ability of the measures. In Study 3, to validate the CATI subscales, the CATI was administered to 195 new individuals along with existing valid measures qualitatively similar to each CATI subscale. Results The CATI showed convergent validity at both the total-scale (r ≥ .79) and subscale level (r ≥ .68). The CATI also showed superior internal reliability for total-scale scores (α = .95) relative to the AQ (α = .90) and BAPQ (α = .94), consistently high reliability for subscales (α > .81), greater predictive ability for classifying autism (Youden’s Index = .62 vs .56–.59), and demonstrated measurement invariance for sex. Limitations Analyses of predictive ability for classifying autism depended upon self-reported diagnosis or identification of autism. The autistic sample was not large enough to test measurement invariance of autism diagnosis. Conclusions The CATI is a reliable and economical new measure that provides observations across a wide range of trait dimensions associated with autism, potentially precluding the need to administer multiple measures, and to our knowledge, the CATI is also the first broad measure of autistic traits to have dedicated subscales for social camouflage and sensory sensitivity.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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Evaluation of 16S rRNA primer sets for characterisation of microbiota in paediatric patients with autism spectrum disorder

Scientific Reports ◽

10.1038/s41598-021-86378-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

L. Palkova ◽

A. Tomova ◽

G. Repiska ◽

K. Babinska ◽

B. Bokor ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

16S Rrna ◽

Dna Amplification ◽

Disease Status ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Sequencing Analysis ◽

Key Factor ◽

Health And Disease ◽

Primer Sets

AbstractAbstract intestinal microbiota is becoming a significant marker that reflects differences between health and disease status also in terms of gut-brain axis communication. Studies show that children with autism spectrum disorder (ASD) often have a mix of gut microbes that is distinct from the neurotypical children. Various assays are being used for microbiota investigation and were considered to be universal. However, newer studies showed that protocol for preparing DNA sequencing libraries is a key factor influencing results of microbiota investigation. The choice of DNA amplification primers seems to be the crucial for the outcome of analysis. In our study, we have tested 3 primer sets to investigate differences in outcome of sequencing analysis of microbiota in children with ASD. We found out that primers detected different portion of bacteria in samples especially at phylum level; significantly higher abundance of Bacteroides and lower Firmicutes were detected using 515f/806r compared to 27f/1492r and 27f*/1495f primers. So, the question is whether a gold standard of Firmicutes/Bacteroidetes ratio is a valuable and reliable universal marker, since two primer sets towards 16S rRNA can provide opposite information. Moreover, significantly higher relative abundance of Proteobacteria was detected using 27f/1492r. The beta diversity of sample groups differed remarkably and so the number of observed bacterial genera.

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Autistic traits in offspring of schizophrenic patients in comparison to those of normal population: a case-control study

Middle East Current Psychiatry ◽

10.1186/s43045-021-00100-0 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Shimaa Ibrahim Amin ◽

Ghada Mohamed Salah EL-Deen

Keyword(s):

Social Class ◽

Autistic Traits ◽

Autism Spectrum ◽

Cutoff Point ◽

Control Group ◽

Case Group ◽

Parental History ◽

Autism Quotient ◽

Wide Range ◽

Schizophrenic Patients

Abstract Background Autism is not a discreet condition and those families members with autistic propend are more likely to display autistic symptoms with a wide range of severity, even below the threshold for diagnosis of autism spectrum disorders. Even with a parental history of schizophrenia, the likelihood of autistic spectrum disorder was found to be 3-fold greater. The aim of this study is to assess autistic traits among offspring of schizophrenic patients in the age group from 4 to 11 years and compare it in the offspring of normal individuals, and its association with the sociodemographic data. To determine whether schizophrenic parents are a risk factor to autistic traits in their children. Results There was a statistically significant (P < 0.05*) increase in Autism Quotient Child scores of the case group where 47.2% had a score equal or more than the cutoff point (76), while only 17 19.4% of the control group had the same score with odds = 3.71 indicating that children of schizophrenic parents 18 were three times likely to have Autism Quotient-Child score greater than or equal to the cutoff point (76) than 19 children of healthy parents. No statistically significant association (P ≥ 0.05) was found between all 20 sociodemographic characteristics and Autism Quotient-Child scores among the case group except for family 21 income and social class where there was a statistically significant association (P < 0.05) between insufficient income 22 and low social class and higher Autism Quotient-Child score (≥ 76). Conclusions Children of schizophrenic parents are at high risk to have autistic traits than children of normal parents.

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