• MeSH
• fyziologie výživy kojenců MeSH
• náhražky mateřského mléka MeSH
• nenasycené mastné kyseliny MeSH
• nutriční nároky MeSH
• vývoj dítěte MeSH

• Konspekt
• Pediatrie
• NLK Obory
• pediatrie
• nutriční terapie, dietoterapie a výživa

Methamphetamine (MA), as massively abused psychoactive stimulant, has been associated with many neurological diseases. It has various potent and neurotoxic properties. There are many mechanisms of action that contribute to its neurotoxic and degenerative effects, including excessive neurotransmitter (NEU) release, blockage of NEU uptake transporters, degeneration of NEU receptors, process of oxidative stress etc. MA intoxication is caused by blood-brain barrier disruption resulted from MA-induced oxidation stress. In our laboratory we constantly work on animal research of MA. Our current interest is to investigate processes of MA-induced alteration in neurotransmission, especially during development of laboratory rat. This review will describe current understanding in role of NEUs, which are affected by MA-induced neurotoxicity caused by altering the action of NEUs in the central nervous system (CNS). It also briefly brings information about NEUs development in critical periods of development.

• MeSH
• centrální nervový systém účinky léků   růst a vývoj   metabolismus   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• methamfetamin toxicita   MeSH
• nervový přenos účinky léků   MeSH
• neurogeneze účinky léků   MeSH
• neurotoxické syndromy etiologie   metabolismus   patologie   MeSH
• neurotransmiterové látky toxicita   MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Adenylosuccinate lyase (ADSL) functions in de novo purine synthesis (DNPS) and the purine nucleotide cycle. ADSL deficiency (ADSLD) causes numerous neurodevelopmental pathologies, including microcephaly and autism spectrum disorder. ADSLD patients have normal serum purine nucleotide levels but exhibit accumulation of dephosphorylated ADSL substrates, S-Ado, and SAICAr, the latter being implicated in neurotoxic effects through unknown mechanisms. We examined the phenotypic effects of ADSL depletion in human cells and their relation to phenotypic outcomes. Using specific interventions to compensate for reduced purine levels or modulate SAICAr accumulation, we found that diminished AMP levels resulted in increased DNA damage signaling and cell cycle delays, while primary ciliogenesis was impaired specifically by loss of ADSL or administration of SAICAr. ADSL-deficient chicken and zebrafish embryos displayed impaired neurogenesis and microcephaly. Neuroprogenitor attrition in zebrafish embryos was rescued by pharmacological inhibition of DNPS, but not increased nucleotide concentration. Zebrafish also displayed phenotypes commonly linked to ciliopathies. Our results suggest that both reduced purine levels and impaired DNPS contribute to neurodevelopmental pathology in ADSLD and that defective ciliogenesis may influence the ADSLD phenotypic spectrum.

• MeSH
• adenylsukcinátlyasa nedostatek   metabolismus   MeSH
• aminoimidazolkarboxamid analogy a deriváty   metabolismus   MeSH
• autistická porucha metabolismus   MeSH
• buněčné linie MeSH
• buněčný cyklus MeSH
• ciliopatie metabolismus   MeSH
• dánio pruhované metabolismus   MeSH
• fenotyp MeSH
• fosfoproteiny metabolismus   MeSH
• kur domácí metabolismus   MeSH
• lidé MeSH
• mikrocefalie metabolismus   MeSH
• neurogeneze * MeSH
• poruchy autistického spektra metabolismus   MeSH
• poruchy metabolismu purinů a pyrimidinů metabolismus   MeSH
• poškození DNA MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• puriny metabolismus   MeSH
• ribonukleotidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

OBJECTIVE: To correlate fetal brain magnetic resonance imaging (MRI) findings with epilepsy characteristics and neurodevelopment at 2 years of age in children with tuberous sclerosis complex (TSC) to improve prenatal counseling. STUDY DESIGN: This retrospective cohort study was performed in a collaboration between centers of the EPISTOP consortium. We included children with definite TSC, fetal MRIs, and available follow-up data at 2 years of age. A pediatric neuroradiologist masked to the patient's clinical characteristics evaluated all fetal MRIs. MRIs were categorized for each of the 10 brain lobes as score 0: no (sub)cortical lesions or doubt; score 1: a single small lesion; score 2: more than one small lesion or at least one large lesion (>5 mm). Neurologic manifestations were correlated to lesion sum scores. RESULTS: Forty-one children were included. Median gestational age at MRI was 33.3 weeks; (sub)cortical lesions were detected in 97.6%. Mean lesion sum score was 4.5. At 2 years, 58.5% of patients had epilepsy and 22% had drug-resistant epilepsy. Cognitive, language, and motor development were delayed in 38%, 81%, and 50% of patients, respectively. Autism spectrum disorder (ASD) was diagnosed in 20.5%. Fetal MRI lesion sum scores were significantly associated with cognitive and motor development, and with ASD diagnosis, but not with epilepsy characteristics. CONCLUSIONS: Fetal cerebral lesion scores correlate with neurodevelopment and ASD at 2 years in children with TSC.

• MeSH
• epilepsie epidemiologie   MeSH
• kognitivní poruchy epidemiologie   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   MeSH
• následné studie MeSH
• neurovývojové poruchy epidemiologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• tuberózní skleróza epidemiologie   MeSH
• vývojové poruchy řeči epidemiologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder with a high risk of early-onset epilepsy and a high prevalence of neurodevelopmental comorbidities, including intellectual disability and autism spectrum disorder (ASD). Therefore, TSC is an interesting disease model to investigate early biomarkers of neurodevelopmental comorbidities when interventions are favourable. We investigated whether early EEG characteristics can be used to predict neurodevelopment in infants with TSC. The first recorded EEG of 64 infants with TSC, enrolled in the international prospective EPISTOP trial (recorded at a median gestational age 42 4/7 weeks) was first visually assessed. EEG characteristics were correlated with ASD risk based on the ADOS-2 score, and cognitive, language, and motor developmental quotients (Bayley Scales of Infant and Toddler Development III) at the age of 24 months. Quantitative EEG analysis was used to validate the relationship between EEG background abnormalities and ASD risk. An abnormal first EEG (OR = 4.1, p-value = 0.027) and more specifically a dysmature EEG background (OR = 4.6, p-value = 0.017) was associated with a higher probability of ASD traits at the age of 24 months. This association between an early abnormal EEG and ASD risk remained significant in a multivariable model, adjusting for mutation and treatment (adjusted OR = 4.2, p-value = 0.029). A dysmature EEG background was also associated with lower cognitive (p-value = 0.029), language (p-value = 0.001), and motor (p-value = 0.017) developmental quotients at the age of 24 months. Our findings suggest that early EEG characteristics in newborns and infants with TSC can be used to predict neurodevelopmental comorbidities.

• Publikační typ
• časopisecké články MeSH

We previously reported the multi-system sequelae of fetal growth restriction, induced by placental underperfusion, in near-term born rabbits, in the immediate neonatal period and up to pre-adolescence. Herein, we describe the pulmonary and neurodevelopmental consequences of FGR in rabbits born preterm. We hypothesize that FGR has an additional detrimental effect on prematurity in both pulmonary function and neurodevelopment. FGR was induced at gestational day (GD) 25 by placental underperfusion, accomplished by partial uteroplacental vessel ligation in one uterine horn. Rabbits were delivered by cesarean section at GD 29, and placentas were harvested for histology. Neonates underwent neurobehavioral or pulmonary functional assessment at postnatal day 1, followed by brain or lung harvesting, respectively. The neurodevelopmental assessment included neurobehavioral testing and multiregional quantification of cell density and apoptosis in the brain. Lung assessment included functional testing, alveolar morphometry, and airway histology. FGR was associated with higher perinatal mortality, lower birth and placental weight, and a similar brain-to-body weight ratio compared to controls. Placental underperfusion decreased labyrinth and junction zone volumes in FGR placentas. FGR impaired pulmonary function, depicted by higher parenchymal resistance, damping, and elastance. Alveolar morphometry and airway smooth muscle content were comparable between groups. Neurobehavioral tests showed motoric and sensorial impairment in FGR rabbits. In FGR brains, cell density was globally reduced, with higher apoptosis in selected areas. In conclusion, in preterm-born rabbits, placental underperfusion leads to higher mortality, FGR, and impaired lung and brain development in early assessment. This study complements previous findings of placental, pulmonary, and neurodevelopmental impairment in near-term born rabbits in this model.

• Publikační typ
• časopisecké články MeSH

Alexander disease (AxD) is a rare and severe neurodegenerative disorder caused by mutations in glial fibrillary acidic protein (GFAP). While the exact disease mechanism remains unknown, previous studies suggest that mutant GFAP influences many cellular processes, including cytoskeleton stability, mechanosensing, metabolism, and proteasome function. While most studies have primarily focused on GFAP-expressing astrocytes, GFAP is also expressed by radial glia and neural progenitor cells, prompting questions about the impact of GFAP mutations on central nervous system (CNS) development. In this study, we observed impaired differentiation of astrocytes and neurons in co-cultures of astrocytes and neurons, as well as in neural organoids, both generated from AxD patient-derived induced pluripotent stem (iPS) cells with a GFAPR239C mutation. Leveraging single-cell RNA sequencing (scRNA-seq), we identified distinct cell populations and transcriptomic differences between the mutant GFAP cultures and a corrected isogenic control. These findings were supported by results obtained with immunocytochemistry and proteomics. In co-cultures, the GFAPR239C mutation resulted in an increased abundance of immature cells, while in unguided neural organoids and cortical organoids, we observed altered lineage commitment and reduced abundance of astrocytes. Gene expression analysis revealed increased stress susceptibility, cytoskeletal abnormalities, and altered extracellular matrix and cell-cell communication patterns in the AxD cultures, which also exhibited higher cell death after stress. Overall, our results point to altered cell differentiation in AxD patient-derived iPS-cell models, opening new avenues for AxD research.

• MeSH
• Alexanderova nemoc * genetika   patologie   metabolismus   MeSH
• astrocyty * metabolismus   patologie   MeSH
• buněčná diferenciace * fyziologie   MeSH
• gliový fibrilární kyselý protein * metabolismus   genetika   MeSH
• indukované pluripotentní kmenové buňky * metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé MeSH
• mutace MeSH
• nervové kmenové buňky metabolismus   MeSH
• neurony metabolismus   patologie   MeSH
• organoidy metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• neurofyziologie - děti - Rettův syndrom - diagnostika - studie,

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• pediatrie
• embryologie a teratologie
• genetika, lékařská genetika

Hypoglykémia je najbežnejšou metabolickou poruchou u novorodencov. Definuje sa ako pokles koncentrácie glukózy pod 2,5 mmol/l nezávisle od gestačného veku. Neliečená hypoglykémia novorodenca môže viesť k narušeniu psychomotorického vývoja. Zvyčajne však hypoglykémia predstavuje ľahko riešiteľný problém. Jej liečba jednoznačne zvyšuje pravdepodobnosť vyššej kvality prežívania dieťaťa. V práci sú uvedené aktuálne poznatky o etiopatogenéze, klinickom obraze, diagnostike, liečbe a prognóze novorodeneckej hypoglykémie.

Hypoglycaemia is the most common metabolic disorder in newborns. It is defined as a blood glucose concentration of less than 2.5 mmol/L that is applicable to any infant whether term or preterm. Untreated hypoglycaemia may result in neurodevelopment impairment. Usually hypoglycaemia represents a problem that can be managed easily. Its treatment clearly improves quality of child's subsequent life. The paper presents current knowledge on etiopathogenesis, clinical picture, diagnosis, treatment and prognosis of neonatal hypoglycaemia.

The knowledge of the effects of organophosphate flame retardants on children's neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children's neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children's urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 μg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 μg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = -1.30; 95%CI = -2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = -0.98; 95%CI = -2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = -1.42; 95% CI = -2.70; -0.06; p-value = 0.04) and no clear association with DPHP (β = -1.09; 95% CI = -2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 μg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 μg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was -0.49 (95%CI = -1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was -0.35 (95%CI = -1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.

• Publikační typ
• časopisecké články MeSH