Gangliosides are major glycans on vertebrate nerve cells, and their metabolic disruption results in congenital disorders with marked cognitive and motor deficits. The sialyltransferase gene
is ...responsible for terminal sialylation of two prominent brain gangliosides in mammals, GD1a and GT1b. In this study, we analyzed the expression of calcium-binding interneurons in primary sensory (somatic, visual, and auditory) and motor areas of the neocortex, hippocampus, and striatum of
-null mice as well as
-null and
-double null. Immunohistochemistry with highly specific primary antibodies for GABA, parvalbumin, calretinin, and calbindin were used for interneuron detection.
-null mice had decreased expression of all three analyzed types of calcium-binding interneurons in all analyzed regions of the neocortex. These results implicate gangliosides GD1a and GT1b in the process of interneuron migration and maturation.
Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation of ...functional neuronal networks. This review focuses on the multifaceted involvement of lipid rafts in key neurodevelopmental processes, including neural differentiation, synaptogenesis and myelination. Through the spatial organisation of signalling components, lipid rafts facilitate precise signalling events that determine neural fate during embryonic development and in adulthood. The evolutionary conservation of lipid rafts underscores their fundamental importance for the structural and functional complexity of the nervous system in all species. Furthermore, there is increasing evidence that environmental factors can modulate the composition and function of lipid rafts and influence neurodevelopmental processes. Understanding the intricate interplay between lipid rafts and neurodevelopment not only sheds light on the fundamental mechanisms governing brain development but also has implications for therapeutic strategies aimed at cultivating neuronal networks and addressing neurodevelopmental disorders.
The aim of this study was to determine the effects of altered ganglioside composition on the expression of Cx37, Cx40, Cx43, Cx45, and Panx1 in different kidney regions of
gene knockout mice (
KO) ...lacking the GD3 synthase enzyme. Experiments were performed in twelve male 6-month-old mice: four wild-type (C57BL/6-type, WT) and eight
KO mice. After euthanasia, kidney tissue was harvested, embedded in paraffin wax, and processed for immunohistochemistry. The expression of connexins and Panx1 was determined in different regions of the kidney: cortex (CTX.), outer stripe of outer medulla (O.S.), inner stripe of outer medulla (IN.S.), and inner medulla (IN.MED.). We determined significantly lower expression of Cx37, Cx40, Cx45, and Panx1 in different parts of the kidneys of
KO mice compared with WT. The most consistent decrease was found in the O.S. where all markers (Cx 37, 40, 45 and Panx1) were disrupted in St8si1 KO mice. In the CTX. region, we observed decrease in the expression of Cx37, Cx45, and Panx1, while reduced expression of Cx37 and Panx1 was more specific to IN.S. The results of the present study suggest that deficiency of GD3 synthase in
KO mice leads to disruption of renal Cx expression, which is probably related to alteration of ganglioside composition.
Chronic stress produces long‐term metabolic changes throughout the superfamily of nuclear receptors, potentially causing various pathologies. Sex hormones modulate the stress response and generate a ...sex‐specific age‐dependent metabolic imprint, especially distinct in the reproductive senescence of females. We monitored chronic stress recovery in two age groups of female Sprague Dawley rats to determine whether stress and/or aging structurally changed the glycolipid microenvironment, a milieu playing an important role in cognitive functions. Old females experienced memory impairment even at basal conditions, which was additionally amplified by stress. On the other hand, the memory of young females was not disrupted. Stress recovery was followed by a microglial decrease and an increase in astrocyte count in the hippocampal immune system. Since dysfunction of the brain immune system could contribute to disturbed synaptogenesis, we analyzed neuroplastin expression and the lipid environment. Neuroplastin microenvironments were explored by analyzing immunofluorescent stainings using a newly developed Python script method. Stress reorganized glycolipid microenvironment in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) hippocampal regions of old females but in a very different fashion, thus affecting neuroplasticity. The postulation of four possible neuroplastin environments pointed to the GD1a ganglioside enrichment during reproductive senescence of stressed females, as well as its high dispersion in both regions and to GD1a and GM1 loss in the CA1 region. A specific lipid environment might influence neuroplastin functionality and underlie synaptic dysfunction triggered by a combination of aging and chronic stress.
Stress causes memory decline in (pre)menopausal female rats. This effect was followed by expressional changes in the lipid environment of the APP, Np65, AMPA‐R, glial cell number and structural changes of membrane lipids in hippocampus. We postulated four possible Np65 environments involving GD1a enrichment and its high dispersion. The specific lipid environment might influence Np65 functionality and could underlie synaptic dysfunction and amyloidogenesis upon aging and stress.
Summary
Background
Research findings of the association and its pattern between obesity and psychiatric/psychological comorbidities are not consistent across the types of comorbidities or the study ...subgroups.
Objectives
We aimed to perform meta‐analysis of cross‐sectional studies and longitudinal studies analysing obesity as a risk factor for conduct disorder in order to assess the association between child/adolescent overweight/obesity and conduct disorder.
Methods
Systematic literature search, study selection and data extraction were performed independently by the two authors. Data were analysed by Comprehensive Meta‐analysis software.
Results
Analysis of 13 high‐quality cross‐sectional studies including 79 027 children and adolescents indicated a significant association between overweight/obesity and conduct disorder among children and adolescents (OR 1.32 95% CI, 1.18‐1.49, I2 = 86.68), with no publication bias. Subgroup analyses yielded a significant difference (P < .01) between boys and girls. Analysis of four low‐ to moderate‐quality longitudinal studies (OR 1.11 95% CI, 0.89‐1.38, I2 = 57.69) showed no prospective association between overweight/obesity and conduct disorder. Subgroup analysis according to gender revealed a significant positive association for boys and negative association for girls.
Conclusions
Based on the high‐quality cross‐sectional data, overweight and obesity are associated with conduct disorder among children and adolescents, affecting boys more frequently than girls. Results of the longitudinal analysis indicated possible association in boys, while girls seem to be protected from conduct disorder. However, these results are very unreliable, indicating the need of well‐designed longitudinal studies to elucidate the pattern of association between these disorders.
Insulin resistance has many deleterious effects on the central nervous system, including the initiation and potentiation of neurodegeneration. While the pathogenesis of Alzheimer's disease has been ...extensively researched with many insights into the effects of amyloids and neurofibrillary tangles, the connection between the two pathogenic entities has not yet been fully elucidated. Gangliosides are commonly found in neuronal membranes and myelin, specifically in lipid rafts that have been linked to pathological amyloidogenesis. In this study, 64 Sprague Dawley rats with equal sex distribution were separated into four sex-specific groups, as follows: control group on standard diet; group on high-fat, high-sugar diet (HFHSD); group on HFHSD treated with metformin; and group on HFHSD treated with liraglutide. Free-floating immunohistochemistry of the rat hippocampi was performed to analyze group-specific and sex-specific changes in the composition of the four most common gangliosides found in neuronal membranes and myelin sheaths, GM1, GD1a, GD1b and GT1b. The groups on HFHSD showed glucose tolerance impairment and body weight increase at the end of the experiment, whereas the groups treated with pharmacotherapeutics had better insulin sensitivity and decreases in body weight by the end of the experiment. Most changes were observed for GM1 and GD1b. Positive immunoreactivity for GM1 was observed in the male group treated with liraglutide in regions where it is not physiologically found. The changes observed following HFHSD and liraglutide treatment were suggestive of ganglioside restructuring that might have implications on pathological amyloidogenesis. Metformin treatment did not significantly alter the hippocampal ganglioside composition in either sex.
The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes.
Elderly Sprague-Dawley ...rats, 45 weeks old, were randomized into four groups: a control group fed on the standard diet (STD), one group fed the HFHSD, and two groups fed the HFHSD along with long-term treatment of either metformin (HFHSD+M) or liraglutide (HFHSD+L). Antidiabetic treatment started 5 weeks after the introduction of the diet and lasted 13 weeks until the animals were 64 weeks old.
Unexpectedly, HFHSD-fed animals did not gain weight but underwent significant metabolic changes. Both antidiabetic treatments produced sex-specific effects, but neither prevented the onset of prediabetes nor diabetes.
Liraglutide vested benefits to liver and skeletal muscle tissue in males but induced signs of insulin resistance in females.
Women’s metabolism during pregnancy undergoes numerous changes that can lead to gestational diabetes mellitus (GDM). The cause and pathogenesis of GDM, a heterogeneous disease, are not completely ...clear, but GDM is increasing in prevalence and is associated with the modern lifestyle. Most diagnoses of GDM are made via the guidelines from the International Association of Diabetes and Pregnancy Study Groups (IADSPG), which involve an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. Diagnosis in this stage of pregnancy can lead to short- and long-term implications for the mother and child. Therefore, there is an urgent need for earlier GDM markers in order to enable prevention and earlier treatment. Routine GDM biomarkers (plasma glucose, insulin, C-peptide, homeostatic model assessment of insulin resistance, and sex hormone-binding globulin) can differentiate between healthy pregnant women and those with GDM but are not suitable for early GDM diagnosis. In this article, we present an overview of the potential early biomarkers for GDM that have been investigated recently. We also present our view of future developments in the laboratory diagnosis of GDM.
Glucose tolerance test (GTT) is standard diagnostic procedure that tests the efficiency of blood glucose-lowering hormones (insulin, incretins, leptin). Contrary, insulin tolerance test (ITT) is ...probing efficiency of blood glucose-rising hormones (glucagon, thyroxine, growth hormone, glucocorticoids, adrenalin, noradrenalin). These two hormone systems together maintain blood glucose levels in a narrow range. Various pathophysiological mechanisms give rise to a reversible condition - prediabetes which then progresses to an irreversible chronic disease - diabetes, both marked with deviation of blood glucose levels outside the set range. In diagnostic purpose, the patient is given glucose load, and blood glucose is measured right before and 2 hours after load. Measurements are more frequent after insulin injection (ITT) or if both tests are performed on experimental animals. In this paper we analyse the mathematical model for GTT and ITT. The obtained model function is an useful tool in describing the dynamics of blood glucose changes.
The study aimed to determine whether the exposure to chronic stress and/or performance of gonadectomy might lead to disturbance in the expression of connexin (Cx) 37, 40 and 43 in the spinal cord ...(SC), as a potential explanation for sex differences in stress-related chronic pain conditions. After the rats were sham-operated or gonadectomized, three 10-day sessions of sham or chronic stress were applied. Immunohistochemistry and transmission electron microscopy (TEM) were used to examine Cx localization and expression in the SC. The gonadectomy resulted in an increase of Cx37 expression in the dorsal horn (DH) of the female rats, but chronic stress suppressed the effects of castration. In male rats, only the combined effects of castration and chronic stress increased Cx37 expression. The influence of chronic stress on the DH Cx40 expression was inversely evident after the castration: increased in the ovariectomized female rats, while decreased in the orchidectomized male rats. We did not find any effect of chronic stress and castration, alone or together, on Cx43 expression in the DH, but the percentage of Cx43 overlapping the astrocyte marker glial fibrillary acidic protein (gfap) increased in the male stressed group after the castration. In conclusion, the association of the chronic stress with sex hormone depletion results in disturbances of the SC Cx expression and might be a possible mechanism of disturbed pain perception after chronic stress exposure.
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