The Role of Dietary Peptides Gluten and Casein in the Development of Autism Spectrum Disorder: Biochemical Perspectives.

This paper examines the role of dietary peptides gluten and casein in modulating brain function in individuals with autism spectrum disorder (ASD) from a biochemical perspective. Neurotransmitter systems and neural networks are crucial for brain function, and alterations at the biochemical level can contribute to the characteristic symptoms and behaviors of ASD. The paper explores how dietary peptides influence neurotransmitter systems and neural networks, highlighting their potential as interventions to improve brain function in ASD. The evidence suggests that dietary peptides can impact neurotransmitter synthesis, release, and receptor interactions, disrupting the balance of neurotransmitter systems and affecting neural network function. The findings underscore the potential of dietary interventions in modulating brain function in ASD and call for further research to elucidate the underlying mechanisms and optimize clinical practice. Considering individual dietary sensitivities and preferences, personalized dietary approaches may be necessary for optimal outcomes. Dietary interventions' timing, duration, and integration with other evidence-based treatments are crucial considerations. Safety considerations and regular monitoring are important to ensure the implementation of dietary interventions safely and effectively.

Linking Environmental Chemicals to Neuroinflammation and Autism Spectrum Disorder: Mechanisms and Implications for Prevention.

This article explores the potential link between endocrine-disrupting chemicals (EDCs), neuroinflammation, and the development of autism spectrum disorder (ASD). Neuroinflammation refers to the immune system's response to injury, infection, or disease in the central nervous system. Studies have shown that exposure to EDCs, such as bisphenol A and phthalates, can disrupt normal immune function in the brain, leading to chronic or excessive neuroinflammation. This disruption of immune function can contribute to developing neurological disorders, including ASD. Furthermore, EDCs may activate microglia, increasing pro-inflammatory cytokine production and astroglia-mediated oxidative stress, exacerbating neuroinflammation. EDCs may also modulate the epigenetic profile of cells by methyltransferase expression, thereby affecting neurodevelopment. This article also highlights the importance of reducing exposure to EDCs and advocating for policies and regulations restricting their use. Further research is needed to understand better the mechanisms underlying the link between EDCs, neuroinflammation, and ASD and to develop new treatments for ASD.

Brain-derived neurotrophic factor (BDNF) in perinatal depression: Side show or pivotal factor?

Perinatal depression is the most common psychiatric complication of pregnancy, with its detrimental effects on maternal and infant health widely underrated. There is a pressing need for specific molecular biomarkers, with pregnancy-related decline in brain-derived neurotrophic factor (BDNF) in the blood and downregulation of TrkB receptor in the brain reported in clinical and preclinical studies. In this review, we explore the emerging role of BDNF in reproductive biology and discuss evidence suggesting its deficiency as a risk factor for perinatal depression. With the increasing evidence for restoration of serum BDNF levels by antidepressant therapy, the strengthening association of perinatal depression with deficiency of BDNF supports its potential as a surrogate endpoint for preclinical and clinical studies.

The synergy of ß amyloid 1-42 and oxidative stress in the development of Alzheimer's disease-like neurodegeneration of hippocampal cells.

Alzheimer's disease (AD) is a type of dementia that affects memory, thinking and behavior. Symptoms eventually become severe enough to interfere with daily tasks. Understanding the etiology and pathogenesis of AD is necessary for the development of strategies for AD prevention and/or treatment, and modeling of this pathology is an important step in achieving this goal. ß-amyloid peptide (Aß) injection is a widely used approach for modeling AD. Nevertheless, it has been reported that the model constructed by injection of Aß in combination with a prooxidant cocktail (ferrous sulfate, Aß, and buthionine sulfoximine (BSO) (FAB)) best reflects the natural development of this disease. The relationship between oxidative stress and Aß deposition and their respective roles in Aß-induced pathology in different animal models of AD have been thoroughly investigated. In the current paper, we compared the effects of Aß 1-42 alone with that of Aß-associated oxidative stress induced by the FAB cocktail on the neurodegeneration of hippocampal cells in vitro. We constructed a FAB-induced AD model using rat primary hippocampal cells and analyzed the contribution of each compound. The study mainly focused on the prooxidant aspects of AD pathogenesis. Moreover, cellular bioenergetics was assessed and routine metabolic tests were performed to determine the usefulness of this model. The data clearly show that aggregated Aß1-42 alone is significantly less toxic to hippocampal cells. Aggregated Aß damages neurons, and glial cells proliferate to remove Aß from the hippocampus. External prooxidant agents (Fe2+) or inhibition of internal antioxidant defense by BSO has more toxic effects on hippocampal cells than aggregated Aß alone. Moreover, hippocampal cells fight against Aß-induced damage more effectively than against oxidative damage. However, the combination of Aß with external oxidative damage and inhibition of internal antioxidant defense is even more toxic, impairs cellular defense systems, and may mimic the late phase of AD-associated cell damage. Our findings strongly indicate a critical role for the combination of Aß and oxidative stress in the development of neurodegeneration in vitro.

Assessment of behavioral, morphological and electrophysiological changes in prenatal and postnatal valproate induced rat models of autism spectrum disorder.

Autism spectrum disorders (ASD) are neurodevelopmental disorders, that are characterized by core symptoms, such as alterations of social communication and restrictive or repetitive behavior. The etiology and pathophysiology of disease is still unknown, however, there is a strong interaction between genetic and environmental factors. An intriguing point in autism research is identification the vulnerable time periods of brain development that lack compensatory homeostatic corrections. Valproic acid (VPA) is an antiepileptic drug with a pronounced teratogenic effect associated with a high risk of ASD, and its administration to rats during the gestation is used for autism modeling. It has been hypothesized that valproate induced damage and functional alterations of autism target structures may occur and evolve during early postnatal life. Here, we used prenatal and postnatal administrations of VPA to investigate the main behavioral features which are associated with autism spectrum disorders core symptoms were tested in early juvenile and adult rats. Neuroanatomical lesion of autism target structures and electrophysiological studies in specific neural circuits. Our results showed that prenatal and early postnatal administration of valproate led to the behavioral alterations that were similar to ASD. Postnatally treated group showed tendency to normalize in adulthood. We found pronounced structural changes in the brain target regions of prenatally VPA-treated groups, and an absence of abnormalities in postnatally VPA-treated groups, which confirmed the different severity of VPA across different stages of brain development. The results of this study clearly show time dependent effect of VPA on neurodevelopment, which might be explained by temporal differences of brain regions' development process. Presumably, postnatal administration of valproate leads to the dysfunction of synaptic networks that is recovered during the lifespan, due to the brain plasticity and compensatory ability of circuit refinement. Therefore, investigations of compensatory homeostatic mechanisms activated after VPA administration and directed to eliminate the defects in postnatal brain, may elucidate strategies to improve the course of disease.

The Involvement of Insulin-Like Growth Factor 1 and Nerve Growth Factor in Alzheimer's Disease-Like Pathology and Survival Role of the Mix of Embryonic Proteoglycans: Electrophysiological Fingerprint, Structural Changes and Regulatory Effects on Neurotrophins.

Alzheimer's disease (AD)-associated neurodegeneration is triggered by different fragments of amyloid beta (Aß). Among them, Aß (25-35) fragment plays a critical role in the development of neurodegeneration-it reduces synaptic integrity by disruption of excitatory/inhibitory ratio across networks and alters the growth factors synthesis. Thus, in this study, we aimed to identify the involvement of neurotrophic factors-the insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF)-of AD-like neurodegeneration induced by Aß (25-35). Taking into account our previous findings on the neuroprotective effects of the mix of proteoglycans of embryonic genesis (PEG), it was suggested to test its regulatory effect on IGF-1 and NGF levels. To evaluate the progress of neurodegeneration, in vivo electrophysiological investigation of synaptic activity disruption of the entorhinal cortex-hippocampus circuit at AD was performed and the potential recovery effects of PEG with relative structural changes were provided. To reveal the direct effects of PEG on brain functional activity, the electrophysiological pattern of the single cells from nucleus supraopticus, sensomotor cortex and hippocampus after acute injection of PEG was examined. Our results demonstrated that after i.c.v. injection of Aß (25-35), the level of NGF decreased in cerebral cortex and hypothalamus, and, in contrast, increased in hippocampus, prompting its multidirectional role in case of brain damage. The concentration of IGF-1 significantly increased in all investigated brain structures. The administration of PEG balanced the growth factor levels accompanied by substantial restoration of neural tissue architecture and synaptic activity. Acute injection of PEG activated the hypothalamic nucleus supraopticus and hippocampal neurons. IGF-1 and NGF levels were found to be elevated in animals receiving PEG in an absence of amyloid exposure. We suggest that IGF-1 and NGF play a critical role in the development of AD. At the same time, it becomes clear that the neuroprotective effects of PEG are likely mediated via the regulation of neurotrophins.

The role of monoamines in the development of Alzheimer's disease and neuroprotective effect of a proline rich polypeptide.

INTRODUCTION: We have analyzed the alterations in the brain monoaminergic system using the rat model of AD-like pathology. In addition, we have investigated potential neuroprotective effects of the hypothalamic proline-rich polypeptide (PRP-1). METHODS: Histochemical staining, HPLC, chemiluminescent and bioluminescence assays. RESULTS: The levels of monoamines in the target AD brain structures were found elevated, except serotonin, which was unaffected in both hippocampus and brainstem and decreased in frontal cortex. This was accompanied by the substantial structural damage of cortical, hippocampal, as well as the monoaminergic neurons of locus coeruleus and oxidative stress. PRP-1 was able to reverse most of these changes. DISCUSSION: The increased levels of major brain monoamines in the model of AD supports the hypothesis of the important role of monoamines in the excessive synaptic excitation resulting in cognitive dysfunction in AD brain. The neuroprotective effect of PRP-1 as manifested by the recovery of monoaminergic system suggests this bioactive compound as a perspective therapeutic agent for the treatment of AD.

Advances in understanding the pathophysiology of autism spectrum disorders.

Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders with typical triad of symptoms: impaired social interaction, language and communication abnormalities and stereotypical behavior. Despite extensive research, the etiology and pathogenesis of ASD remain largely unclear. The lack of solid knowledge on the mechanisms of these disorders decreases the opportunities for pathogenetic treatment of autism. Various theories where proposed in order to explain the pathophysiology underlying ASD. Despite the fact that none of them is able to completely explain the impairments in the nervous system of ASD patients, these hypotheses were instrumental in highlighting the most important mechanisms in the development of this complex disorder. Some new theories are based on neurovisualization studies, others on the data from genomic studies, which become increasingly available worldwide. As the research in this field is largely dependent on the animal models, there is an ongoing discussion and search for the most appropriate one adequately reproducing the pathology. Here we provide an overview of current theories of the origin and development of ASD discussed in the context of existing and proposed rodent models of ASD.