Репозиторий Университета

© 2019 Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.

© 2019 Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.

© 2019 Elsevier Ltd Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum. Adgrl3 −/− mice show increased locomotive activity across all tests and subtle gait abnormalities. These mice also show impairments across spatial memory and learning domains, alongside increased levels of impulsivity and sociability with decreased aggression. However, these alterations were absent in Adgrl3 +/− mice. Across all brain regions tested, the numbers of genes found to exhibit differential expression was relatively small, indicating a specific pathway of action, rather than a broad neurobiological perturbation. Gene-set analysis of differential expression in the PFC detected a number of ADHD-relevant pathways including dopaminergic synapses as well as cocaine and amphetamine addiction. The Slc6a3 gene coding for the dopamine transporter was the most dysregulated gene in the PFC. Unexpectedly, several neurohormone/peptides which are typically only expressed in the hypothamalus were found to be dysregulated in the striatum. Our study further validates Adgrl3 constitutive knockout mice as an experimental model of ADHD while providing neuroanatomical targets for future studies involving ADGRL3 modified models. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

© 2019, Pediatria Ltd. All rights reserved. Attention deficit hyperactivity disorder (ADHD) is an urgent problem due to the high incidence rate, reaching 3–5% in the child population. The article discusses diagnostic criteria for ADHD and manifestation peculiarities in different age periods. It also duscusses etiopathogenesis of ADHD as a multifactorial developmental disorder; reviews main groups of drugs used for the pharmacological correction of the disease, among which nootropics, in particular aminophenylbutyric acid («Anvifen»), occupy a special place. Author discusses and justifies the need for an integrated approach to ADHD treatment, which should combine pharmacotherapy, neuropsychological correction and psychotherapy with a child, parents and teachers.

© 2018, ABV-Press Publishing House. Attention deficit hyperactivity disorder (ADHD) is the most common cause of behavioral disorders and learning difficulties in preschool and school-age children. Patients with ADHD are often diagnosed with concomitant diseases, which creates additional diagnostic and therapeutic challenges and leads to a more significant reduction in the quality of life. ADHD is often associated with epilepsy: ADHD manifestations are more common in individuals with epilepsy, and vice versa, patients with ADHD are more likely to have epilepsy. The estimated prevalence of ADHD in children is 7-9 %, whereas in children with epilepsy, it reaches 20-50 %. Epilepsy is also one of the most common diseases in children (affecting approximately 1 % of the pediatric population), which is often aggravated by concomitant diseases, including cognitive, behavioral and emotional disorders. Various factors, such as characteristics of epileptic process and lesions in particular portions of the brain, can underlie the development of ADHD in epilepsy. Epileptiform activity and adverse effects of antiepileptic drugs can also play an important etiological role. Some antiepileptic drugs (such as barbiturates) may cause symptoms similar to those in ADHD (in this case, inattentiveness and hyperactivity shall be considered as adverse events that can be reduced or eliminated after cessation of the drug) or exacerbate ADHD symptoms in patients with these disorders. Therefore, the drugs with no negative impact on concomitant diseases or with a positive therapeutic effect for both diseases are preferable in these cases. High prevalence of the ADHD/epilepsy combination leads to a greater reduction in the quality of life, suggesting high relevance of this problem and requiring a revision of therapeutic approaches.