Establishment of animal models and behavioral studies for autism spectrum disorders.

In recent years, the incidence of autism spectrum disorder (ASD) has increased, but the etiology and pathogenesis remain unclear. In this narrative review, we review and systematically summarize the methods used to construct animal models to study ASD and the related behavioral studies based on recent literature. Utilization of various ASD animal models can complement research on the etiology, pathogenesis, and core behaviors of ASD, providing information and a foundation for further basic research and clinical treatment of ASD.

Erratum: Pertinence of glioma and single nucleotide polymorphism of TERT, CCDC26, CDKN2A/B, and RTEL1 genes in glioma: a meta-analysis.

[This corrects the article DOI: 10.3389/fonc.2023.1180099.].

Genetic Analyses of Flower Main Traits from Two Pitayas and Their Progenies: A Cactus Plant.

Elucidation of the genetic foundation governing crucial traits in pitaya flowers is imperative for enhancing both the ornamental and economic values. In this study, the dynamic variation in flower genetics, segregation variation patterns, and a mixed inheritance model of the major and multigene flower traits of 'Dahong' and 'Honghuaqinglong' pitayas and their progenies were explored. The results showed that the main traits of flowers exhibited varying degrees of variation among the reciprocal F1 hybrids, with the data exhibiting the characteristics of quantitative traits. The betalain content, petal number, and stigma number exhibited values below the median values of the parents, suggesting a genetic inclination towards lower values. Perianth width, calyx tube width, petal number, and stigma number had the same genetic effects and significant correlation. Stigma-related traits had a clear maternal inheritance tendency. The heritability of flower length, stigma relative to anther distance, and petal betalain content was governed by two pairs of additive-dominant major genes. Perianth width, calyx tube width, petal number, and stigma number all conformed to the model of two pairs of equal-additive-dominant major genes. This study provides valuable information for parental selection, cross-breeding, and the enhancement of pitaya varieties to meet market preferences and environmental conditions.

A fast algorithm to factorize high-dimensional tensor product matrices used in genetic models.

Many genetic models (including models for epistatic effects as well as genetic-by-environment) involve covariance structures that are Hadamard products of lower rank matrices. Implementing these models requires factorizing large Hadamard product matrices. The available algorithms for factorization do not scale well for big data, making the use of some of these models not feasible with large sample sizes. Here, based on properties of Hadamard products and (related) Kronecker products, we propose an algorithm that produces an approximate decomposition that is orders of magnitude faster than the standard eigenvalue decomposition. In this article, we describe the algorithm, show how it can be used to factorize large Hadamard product matrices, present benchmarks, and illustrate the use of the method by presenting an analysis of data from the northern testing locations of the G × E project from the Genomes to Fields Initiative (n ∼ 60,000). We implemented the proposed algorithm in the open-source "tensorEVD" R package.

Genetic Model Identification and Major QTL Mapping for Petiole Thickness in Non-Heading Chinese Cabbage.

Petioles of non-heading Chinese cabbage are not only an important edible part but also a conduit for nutrient transport, holding significant agricultural and research value. In this study, we conducted a comprehensive genetic analysis of petiole-related traits using a segregating population. Modern quantitative genetic approaches were applied to investigate the genetic regulation of petiole thickness. The results indicated that petiole thickness is a quantitative trait, and the identified genetic model was consistent with two pairs of additive-dominant main genes and additive-dominant polygenes (2MG-AD). BSA-seq analysis identified a major effect of QTL controlling petiole thickness on chromosome A09: 42.08-45.09 Mb, spanning 3.01 Mb, designated as QTL-BrLH9. Utilizing InDel markers, the interval was narrowed down to 51 kb, encompassing 14 genes with annotations for 10 of them. Within the interval, four mutated genes were detected. Combined with gene annotation, protein sequence analysis, and homology alignment, it was found that BraA09g063520.3C's homologous gene SMXL6 in Arabidopsis (Arabidopsis thaliana (L.) Heynh) is an inhibitor of the coding and synthesis of the strigolactone pathway. Strigolactone (SLs) plays an important role in plant growth and development. The cloning results showed that multiple frameshift mutations and non-synonymous mutations occurred on the exon. The qPCR results showed that the expression of the gene was significantly different between the two parents at the adult stage, so it was speculated that it would lead to changes in petiole thickness. BraA09g063520.3C was predicted as the final candidate gene.

Non-invasive systemic viral delivery of human alpha-synuclein mimics selective and progressive neuropathology of Parkinson's disease in rodent brains.

BACKGROUND: Alpha-synuclein (α-syn) aggregation into proteinaceous intraneuronal inclusions, called Lewy bodies (LBs), is the neuropathological hallmark of Parkinson's disease (PD) and related synucleinopathies. However, the exact role of α-syn inclusions in PD pathogenesis remains elusive. This lack of knowledge is mainly due to the absence of optimal α-syn-based animal models that recapitulate the different stages of neurodegeneration. METHODS: Here we describe a novel approach for a systemic delivery of viral particles carrying human α-syn allowing for a large-scale overexpression of this protein in the mouse brain. This approach is based on the use of a new generation of adeno-associated virus (AAV), AAV-PHP.eB, with an increased capacity to cross the blood-brain barrier, thus offering a viable tool for a non-invasive and large-scale gene delivery in the central nervous system. RESULTS: Using this model, we report that widespread overexpression of human α-syn induced selective degeneration of dopaminergic (DA) neurons, an exacerbated neuroinflammatory response in the substantia nigra and a progressive manifestation of PD-like motor impairments. Interestingly, biochemical analysis revealed the presence of insoluble α-syn oligomers in the midbrain. Together, our data demonstrate that a single non-invasive systemic delivery of viral particles overexpressing α-syn prompted selective and progressive neuropathology resembling the early stages of PD. CONCLUSIONS: Our new in vivo model represents a valuable tool to study the role of α-syn in PD pathogenesis and in the selective vulnerability of nigral DA neurons; and offers the opportunity to test new strategies targeting α-syn toxicity for the development of disease-modifying therapies for PD and related disorders.

Experimental diabetic animal models to study diabetes and diabetic complications.

Diabetes is an endocrine illness involving numerous physiological systems. To understand the intricated pathophysiology and disease progression in diabetes, small animals are still the most relevant model systems, despite the availability and progression in numerous invitro and insilico research methods in recent years. In general, experimental diabetes is instigated mainly due to the effectiveness of animal models in illuminating disease etiology. Most diabetes trials are conducted on rodents, while some research is conducted on larger animals. This review will discuss the methodology and mechanisms in detail for preparing diabetic animal models, considering the following important points. The exact pathophysiology of the disease may or may not be replicated in animal models, the correct induction doses must be given and the combination of different approaches for the models is recommended to get desired results.•Animal models are essential to understand diabetes etiology and pathophysiology.•Diabetic models can be developed in both rodents and non-rodents.•Chemically induced and genetic models of diabetes are widely used to study diabetes and diabetic complications.

Pertinence of glioma and single nucleotide polymorphism of TERT, CCDC26, CDKN2A/B and RTEL1 genes in glioma: a meta-analysis.

Background: Previous genetic-epidemiological studies considered TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) gene polymorphisms as the risk factors specific to glioma. However, the data samples of previous genetic-epidemiological studies are modest to determine whether they have definite association with glioma. Method: The study paid attention to systematically searching databases of PubMed, Embase, Web of Science (WoS), Scopus, Cochrane Library and Google Scholars. Meta-analysis under 5 genetic models, namely recessive model (RM), over-dominant model (O-DM), allele model (AM), co-dominant model (C-DM) and dominant model (DM) was conducted for generating odds ratios (ORs) and 95% confidence intervals (CIs). That was accompanied by subgroup analyses according to various racial groups. The software STATA 17.0 MP was implemented in the study. Result: 21 articles were collected. According to data analysis results, in four genetic models (AM, RM, DM and C-DM) TERT gene rs2736100 polymorphism, CCDC26 gene rs4295627 polymorphism, CDKN2A/B gene rs4977756 polymorphism and RTEL1 gene rs6010620 polymorphisms increased the risk of glioma in Caucasians to different degrees. In Asian populations, the CCDC26 gene rs4295627 polymorphism and CDKN2A/B gene rs4977756 polymorphism did not exhibit a relevance to the risk of glioma. It is suggested to cautiously explain these results as the sample size is small. Conclusion: The current meta-analysis suggested that the SNP of TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) genes in glioma might increase risk of glioma, but there are ethnic differences. Further studies evaluating these polymorphisms and glioma risk are warranted.

Heart rate reduction after genetic ablation of L-type Cav1.3 channels induces cardioprotection against ischemia-reperfusion injury.

Background: Acute myocardial infarction (AMI) is the major cause of cardiovascular mortality worldwide. Most ischemic episodes are triggered by an increase in heart rate, which induces an imbalance between myocardial oxygen delivery and consumption. Developing drugs that selectively reduce heart rate by inhibiting ion channels involved in heart rate control could provide more clinical benefits. The Cav1.3-mediated L-type Ca2+ current (ICav1.3) play important roles in the generation of heart rate. Therefore, they can constitute relevant targets for selective control of heart rate and cardioprotection during AMI. Objective: We aimed to investigate the relationship between heart rate and infarct size using mouse strains knockout for Cav1.3 (Cav1.3-/-) L-type calcium channel and of the cardiac G protein gated potassium channel (Girk4-/-) in association with the funny (f)-channel inhibitor ivabradine. Methods: Wild-type (WT), Cav1.3+/-, Cav1.3-/- and Girk4-/- mice were used as models of respectively normal heart rate, moderate heart rate reduction, bradycardia, and mild tachycardia, respectively. Mice underwent a surgical protocol of myocardial IR (40 min ischemia and 60 min reperfusion). Heart rate was recorded by one-lead surface ECG recording, and infarct size measured by triphenyl tetrazolium chloride staining. In addition, Cav1.3-/- and WT hearts perfused on a Langendorff system were subjected to the same ischemia-reperfusion protocol ex vivo, without or with atrial pacing, and the coronary flow was recorded. Results: Cav1.3-/- mice presented reduced infarct size (-29%), while Girk4-/- displayed increased infarct size (+30%) compared to WT mice. Consistently, heart rate reduction in Cav1.3+/- or by the f-channel blocker ivabradine was associated with significant decrease in infarct size (-27% and -32%, respectively) in comparison to WT mice. Conclusion: Our results show that decreasing heart rate allows to protect the myocardium against IR injury in vivo and reveal a close relationship between basal heart rate and IR injury. In addition, this study suggests that targeting Cav1.3 channels could constitute a relevant target for reducing infarct size, since maximal heart rate dependent cardioprotective effect is already observed in Cav1.3+/- mice.

Inheritance of Partial Resistance to Isolate VdLs17 of Verticillium dahliae Within Lactuca spp.

Lettuce (Lactuca sativa L.) production is greatly threatened by Verticillium wilt, which is caused by three pathogenic races (races 1, 2, and 3) of the soilborne fungus Verticillium dahliae. Race 1 is predominant, and resistant varieties that provide full protection against it are commercially available. However, heavily relying on race 1-resistant cultivars could shift the population towards resistance-breaking isolates and impact the durability of plant resistance. This study determined the inheritance of partial resistance to isolate VdLs17 of V. dahliae within Lactuca spp. using 258 F2:3 progeny generated from a cross between two partially resistant accessions, 11G99 (L. serriola) and PI 171674 (L. sativa). Eight experiments were performed under greenhouse and growth room conditions across 3 years using a randomized complete block design, and segregation analysis was conducted to determine the inheritance pattern. The results indicate that partial resistance to isolate VdLs17 of V. dahliae is conditioned by a two-major-gene genetic model with additive-dominance-epistatic effects. Transgressive segregants were infrequent but observed in both directions, indicating that favorable and adverse alleles are dispersed in both parents. Combining favorable alleles of these two partially resistant parents appears to be challenging because of epistatic effects and a significant role of environment in disease severity. The probability of capturing favorable additive genes could be maximized by generating and evaluating a large population and making selections at late generations. This study provides valuable insights into the inheritance pattern of partial resistance to isolate VdLs17 of V. dahliae that will be helpful in designing efficient breeding strategies in lettuce.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Remodeling male coercion and the evolution of sexual autonomy by mate choice.

Models of sexual conflict over mating, including conflict over indirect benefits of mate choice, have generally presumed that female resistance to male coercion must involve direct confrontation, which can lead to sexually antagonistic coevolutionary arms-races. We built a quantitative model examining the largely ignored possibility that females may evolve new, additional mate preferences for new male traits that undermine male capacity to coerce. Thus, females may "remodel" the coercive capacity of the male phenotype in order to enhance their own sexual autonomy-a novel alternative mechanism by which females may avoid arms-races. We demonstrate that evolutionary "remodeling" is possible, in spite of costs to males, because females that prefer males with protective, autonomy-enhancing traits (traits correlated with lower coercion effectiveness) are likelier to gain indirect benefits of having attractive mates. Our analysis reveals new possibilities for the evolution of systems of sexual conflict over indirect benefits, showing that autonomy-enhancing male traits can act as a "public good," benefiting all females regardless of mating preferences, leading to oscillatory dynamics; and that preferences for more protective male traits will often be favored relative to preferences for less protective traits, potentially leading to an evolutionary "snowball" of expanding sexual autonomy.

Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights into Pink1 knockout models.

Parkinson's disease (PD) relates to defective mitochondrial quality control in the dopaminergic motor network. Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset, pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra (SNpc). In a reciprocal manner, LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation. Pharmacological intervention in these disease-modifying pathways may facilitate the development of novel PD therapeutics, despite the current lack of an established drug evaluation model. As such, we reviewed the feasibility of employing the versatile global Pink1 knockout (KO) rat model as a self-sufficient, spontaneous PD model for investigating both disease etiology and drug pharmacology. These rats retain clinical features encompassing basal mitophagic flux changes with PD progression. We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.

The Fisher process of sexual selection with the coevolution of preference strength.

Sexual selection has a rich history of mathematical models that consider why preferences favor one trait phenotype over another (for population genetic models) or what specific trait value is preferred (for quantitative genetic models). Less common is exploration of the evolution of choosiness or preference strength: i.e., by how much a trait is preferred. We examine both population and quantitative genetic models of the evolution of preferences, specifically developing "baseline models" of the evolution of preference strength during the Fisher process. Using a population genetic approach, we find selection for stronger and stronger preferences when trait variation is maintained by mutation. However, this force is quite weak and likely to be swamped by drift in moderately-sized populations. In a quantitative genetic model, unimodal preferences will generally not evolve to be increasingly strong without bounds when male traits are under stabilizing viability selection, but evolve to extreme values when viability selection is directional. Our results highlight that different shapes of fitness and preference functions lead to qualitatively different trajectories for preference strength evolution ranging from no evolution to extreme evolution of preference strength.

Estimating the role of single-nucleotide polymorphism (rs1800629)-308 G/A of TNF-alpha gene as genetic marker associated with angina pectoris in a sample of Iraqi patients.

BACKGROUND: Angina pectoris (AP) occurs when oxygen and other nutrients are insufficient to meet the metabolic needs of the heart muscle. Stable angina is the most common, while the unstable angina is less frequent. Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine plays a vital function in the immune response regulation. TNF gene cluster contains many polymorphisms; the most commonly investigated polymorphism is the rs1800629 SNP. This SNP, located at - 308 position with regard to the TNF promoter region, replaces guanine (G) with adenine (A), with the allelic types - 308 G/A, and has been linked to a variety of inflammatory condition and autoimmune diseases. The - 308 G/A SNP was investigated in AP and interconnected to the TNF level to figure out the responsibilities of TNF-alpha gene polymorphism in the pathogenesis of AP. METHOD: The current work design as a case-control study that involves 300 participant divided to 200 patients evaluated as (stable angina n = 100 and unstable angina n = 100) compared with 100 apparently healthy control subjects. The serum level of TNF-alpha was assessed via enzyme-linked immunosorbent assay (ELISA)/sandwich method. The genotype and allele frequency distribution of TNF-alpha rs1800629 gene polymorphism were investigated by TaqMan probe of allelic discrimination method. RESULTS: The levels of TNF-alpha were significantly higher in patients with stable and unstable angina pectoris in comparison with controls. The deviation from Hardy-Weinberg equilibrium (HWE) of TNF-alpha genotypes was obvious in control and unstable angina pectoris groups. Moreover, the significant differences between patients with AP and controls under the five genetic models consider the association between TNF-alpha (rs1800629) - 308 G/A and AP with OR > 1. However, data analysis of allelic and genotypic of (rs1800629) - 308 G/A revealed higher significantly differences of GG homozygous and GA heterozygous proportions between stable angina patients and control. The A allele was more represented as etiological allele, and G allele was represented as protective allele. The serum levels of TNF-alpha were significantly higher in subjects with genetically mutated AA genotypes than in subjects with wild GG genotypes in the study groups. ROC curve analysis found the best cutoff value of TNF-alpha level was 77.25 pg/ml. CONCLUSION: As the results, our data observed a linked of TNF-alpha (rs1800629) - 308 G/A genetic variant with angina pectoris patients, and the A allele has been linked to the production or expression of TNF-alpha serum level and represented an etiological factor of angina pectoris.

Research Development in Patients with Olmsted Syndrome / 罕见病研究

Olmsted syndrome (OS) is an extremely rare hereditary skin disease, that is usually characterized by mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques. The diagnosis of this disease depends primarily on the clinical presentation and OS has to be differentiated from other disorders associated with hyperkeratosis. In recent years, there have been many advances in molecular genetic research on the pathogenesis of the disease. The genes that can cause disease after specific mutations include TRPV3, MBTPS2/S2P and PERP. Therefore, genetic testing has become one of the important methods for the diagnosis of this disease.OS treatment is difficult, and conventional therapy uses topical drugs to soften the cuticle of the skin, or oral Avi A.Excision of palmoplantar keratosis may also be used for constricting rings that severely restrict movement, but they often reoccur after initial improvement. In terms of precision treatment, researchers have tried the small molecule drugs erlotinib and sirolimus and have achieved some results. This paper summarizes the etiology, pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of OS, in order to improve the clinicans' awareness of OS.

Research on genetic model of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of genetic factors on the pathogenesis of keratoconus and its genetic model.METHODS: Genetic epidemiological methods were used to investigate the prevalence of keratoconus in 280 first-degree relatives of 100 patients with keratoconus who attended Henan Eye Hospital between July 2020 and April 2023. The heritability was estimated by Falconer regression method. The general genetic model was calculated using Penrose method, and the genetic model was confirmed by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory.RESULTS: The results showed that there were 16(5.714%)first-degree relatives of keratoconus probands suffering from keratoconus, and the heritability of keratoconus was(86.100±7.400)%. The S/q score calculated by the Penrose method was 35.348, which was near to 1/(q)1/2, suggesting that the genetic model of keratoconus might be polygenic inheritance. The expected prevalence in first-degree relatives of keratoconus patients by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory were 5.900%, 7.714% and 5.700%, respectively, which showed no significant differences from the actual prevalence(5.714%), suggesting that keratoconus was a polygenetic disease.CONCLUSION:Genetic factors might play an important role in the pathogenesis of keratoconus, and keratoconus is a polygenetic disease.

A novel model based on immune-related genes for differentiating biliary atresia from other cholestatic diseases.

PURPOSE: Based on a public gene expression database, this study established the immune-related genetic model that distinguished BA from other cholestasis diseases (DC) for the first time. We explored the molecular mechanism of BA based on the gene model. METHODS: The BA microarray dataset GSE46960, containing BA, other cause of intrahepatic cholestasis than biliary atresia and normal liver gene expression data, was downloaded from the Gene Expression Omnibus (GEO) database. We performed a comprehensive bioinformatics analysis to establish and validate an immune-related gene model and subsequently identified hub genes as biomarkers associated with the molecular mechanisms of BA. To assess the model's performance for separating BA from other cholestasis diseases, we used receiver operating characteristic (ROC) curves and the area under the curve (AUC) of the ROC. Independent datasets GSE69948 and GSE122340 were used for the validation process. RESULTS: The model was built using eight immune-related genes, including EDN1, HAMP, SAA1, SPP1, ANKRD1, MMP7, TACSTD2, and UCA1. In the GSE46960 and validation group, it presented excellent results, and the prediction accuracy of BA in comparison to other cholestasis diseases was good. Functional enrichment analysis revealed significant immunological differences between BA and other cholestatic diseases. Finally, we found that the TNFα-NF-κB pathway is associated with EDN1 gene expression and may explain fibrosis progression, which may become a new therapeutic target. CONCLUSION: In summary, we have successfully constructed an immune-related gene model that can distinguish BA from other cholestatic diseases, while identifying the hub gene. Our exploration of immune genes provides new clues for the early diagnosis, molecular mechanism, and clinical treatment of biliary atresia.

The nematode Oscheius tipulae as a genetic model for programmed DNA elimination.

Programmed DNA elimination (PDE) is a notable exception to the paradigm of genome integrity. In metazoa, PDE often occurs coincident with germline to somatic cell differentiation. During PDE, portions of genomic DNA are lost, resulting in reduced somatic genomes. Prior studies have described the sequences lost, as well as chromosome behavior, during metazoan PDE. However, a system for studying the mechanisms and consequences of PDE in metazoa is lacking. Here, we present a functional and genetic model for PDE in the free-living Rhabditidae nematode Oscheius tipulae, a family that also includes Caenorhabditis elegans. O. tipulae was recently suggested to eliminate DNA. Using staged embryos and DNA FISH, we showed that O. tipulae PDE occurs during embryogenesis at the 8-16 cell stages. We identified a conserved motif, named Sequence For Elimination (SFE), for all 12 break sites on the six chromosomes at the junctions of retained and eliminated DNA. SFE mutants exhibited a "fail-to-eliminate" phenotype only at the modified sites. END-seq revealed that breaks can occur at multiple positions within the SFE, with extensive end resection followed by telomere addition to both retained and eliminated ends. We identified many functional SFEs at the chromosome ends through END-seq in the wild-type embryos, genome sequencing of SFE mutants, and comparative genomics of 23 wild isolates. We suggest that these alternative SFEs provide flexibility in the sequences eliminated and a fail-safe mechanism for PDE. These studies establish O. tipulae as a new, attractive model for studying the mechanisms and consequences of PDE in a metazoan.

Genetic variation in DPP-IV gene linked to predisposition of T2DM: A case control study.

Purpose: DPP-IV is a ubiquitously expressed cell surface protein that can be presented in soluble forms. It has recently gained medical importance as its inhibitors are widely being used as treatment of T2DM. The present research aims to resolve whether genetic variants of DPP-IV have association with susceptibility to T2DM. Method: Two variants of DPP-IV were detected in 100 controls and 100 T2DM by PCR-RFLP technique. Demographic characteristics were recorded. Clinical characteristics were analyzed by enzymatic method. Statistical analysis was performed using SPSS-21. Results: Demographic and clinical characteristics differ significantly between two groups. The genetic variation in SNP rs3788979 and SNP rs7608798, both in case and control, were in accordance with Hardy-Weinberg Equilibrium (p value > 0.05). Both SNPs rs3788979 and rs7608798 were significantly related to T2DM (p- < 0.05). Minor G allele of rs3788979 was linked with the susceptibility of T2DM (p-value-0.000; OR- 4.235). T allele of SNP rs7608798 conferred the risk of diabetes with OR-2.235. Conclusion: This is the first attempt to investigate the association of DPP-IV gene with T2DM in Indian population. The finding of study concludes that genetic variation in DPP-IV gene may considerably increase the risk of developing T2DM.

Maternal Methyl-Enriched Diet Increases Dopaminergic Tone of the Mesolimbic Brain System in Adult Offspring of WAG/Rij Rats.

The aim of this study is to find out whether maternal methyl-enriched diet affects the content of monoamines and their metabolites in brain structures of adult WAG/Rij offspring. It has been shown for the first time that maternal methyl-enriched diet (choline, betaine, folic acid, vitamin B12, L-methionine, zink) during the perinatal period increases dopaminergic tone of the mesolimbic brain system in adult offspring of WAG/Rij rats, which is accompanied by the suppression of the symptoms of genetic absence epilepsy and comorbid depression. Results suggest that maternal methyl-enriched diet during the perinatal period may be served as a new therapeutic strategy to prevent the development of a hypofunction of the mesolimbic dopaminergic brain system and associated genetic absence epilepsy and comorbid depression in offspring.