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Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience


Hyperargininemia is an inborn error of metabolism (IEM) characterized by tissue accumulation of arginine (Arg). Mental retardation and other neurological features are common symptoms in hyperargininemic patients. Considering purinergic signaling has a crucial role from the early stages of development and underlying mechanisms of this disease are poorly established, we investigated the effect of Arg administration on locomotor activity, morphological alterations, and extracellular nucleotide hydrolysis in larvae and adult zebrafish. We showed that 0.1 mM Arg was unable to promote changes in locomotor activity. In addition, 7-day-post-fertilization (dpf) larvae treated with Arg demonstrated a decreased body size. Arg exposure (0.1 mM) promoted an increase in ATP, ADP, and AMP hydrolysis when compared to control group. These findings demonstrated that Arg might affect morphological parameters and ectonucleotidase activities in zebrafish larvae, suggesting that purinergic system is a target for neurotoxic effects induced by Arg.

Concepts: Adenosine triphosphate, Effect, Fish, Affect, Zebrafish, Danio kyathit, Inborn error of metabolism, Danios


Intrauterine exposure of term and premature infants to infection/inflammation may increase the risk of perinatal brain injury, which may be more serious than that incurred by interpartum exposure to hypoxia-ischemia (HI). Many microorganisms, including certain viruses, protozoa, and bacteria, have been linked to this injury. In regard to the mechanisms of intrauterine infection-triggered brain injury, the inflammatory risk factors such as cytokines play a central role. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Studies have reported that polymorphism of cytokine genes also has been implicated in perinatal brain injury. Moreover, inflammation and HI may be synergistically involved in this process. Although the relationship between inflammation and adverse neurodevelopmental outcome in affected infants is slowly being elucidated, the literature contains scant evidence of measures that can improve fetal neurologic outcome. Several pharmacologic molecules such as magnesium sulphate, erythropoietin, and corticosteroids as a neuroprotective agent for the fetus need further investigation.

Concepts: Pregnancy, Childbirth, Bacteria, Asthma, Embryo, Fetus, Uterus, Neurology


The starting point for any research on Autism Spectrum Disorder (ASD) involves the identification of people who evince the condition. From this point flows research on symptom presentation, genetics, epidemiology, animal models, treatment efficacy, and many other important topics. Major advances have been made in differential diagnosis, particularly with young children. This fact is particularly important since ASD is a life long condition. This review documents recent advances and the current state of research on this topic.

Concepts: Medical terms, Medical diagnosis, Autism, Pervasive developmental disorder, Asperger syndrome, Autism spectrum, PDD-NOS, Differential diagnosis


It is well known that events which occur in early life exert a significant influence on brain development, what can be reflected throughout adulthood. This study was carried out in order to assess the influence of neonatal tactile stimulation (TS) on behavioral and morphological responses related to depression-like and anxiety-like behaviors, assessed following the administration of sertraline (SERT), a selective serotonin re-uptake inhibitor (SSRI). Male pups were submitted to daily TS, from postnatal day 8 (PND8) to postnatal day 14 (PND14), for 10min every day. On PND50, adult animals were submitted to forced swimming training (15min). On PND51, half of each experimental group (UH and TS) received a single sub-therapeutic dose of sertraline (SER, 0.3mg/kg body weight, i.p.) or its vehicle (C, control group). Thirty minutes after injection, depression-like behaviors were quantified in forced swimming test (FST, for 5min). On the following day, anxiety-like behaviors were assessed in elevated plus maze (EPM), followed by biochemical assessments. TS per se increased swimming time, decreasing immobility time in FST. Besides, TS per se was able to increase frequency of head dipping and time spent in the open arms of EPM, resulting in decreased anxiety index. In addition, groups exposed to TS showed decreased plasma levels of corticosterone per se. Interestingly, while TS exposure significantly potentiated the antidepressant activity of a subtherapeutic dose of SERT, this drug was able to exacerbate TS-induced anxiolytic activity, as observed in FST and EPM, respectively. Decreased plasma levels of both corticosterone and cortisol in animals exposed to TS and treated with SERT are able to confirm the interesting interaction between this neonatal handling and the antidepressant drug. From our results, we conclude that neonatal TS is able to exert beneficial influence on the ability to cope with stressful situations in adulthood, preventing depression and favorably modulating the action of antidepressant drugs.

Concepts: Serotonin, Antidepressant, Selective serotonin reuptake inhibitor, Bupropion, Sertraline, Tricyclic antidepressant, Fluoxetine, Paroxetine


The ketogenic diet, low in carbohydrates and high in fat, was initially designed to reduce seizure onset in epilepsy. More recent evidence has shown its effectiveness in the treatment of movement and psychological disorders, and in general health maintenance. The cellular significance of ketone body metabolism during development and in the adult central nervous system is being revealed; however, the effects of replacing glucose with ketone bodies as the brains primary energy source especially in pregnancy are not fully understood. In this mini-review, we highlight key findings related to the functional consequences of ketone body metabolism and monocarboxylic transporter expression throughout development and adulthood. We outline the therapeutic relevance of ketone bodies, and place a spotlight on the known effects of a maternal ketogenic diet on the developing brain.

Concepts: Central nervous system, Nervous system, Brain, Metabolism, Nutrition, Ketone, Ketone bodies, Carbohydrate


Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders that is among the most severe in terms of prevalence, morbidity and impact to the society. It is characterized by complex behavioral phenotype and deficits in both social and cognitive functions. Although the exact cause of ASD is still not known, the main findings emphasize the role of genetic and environmental factors in the development of autistic behavior. Environmental factors are also likely to interact with the genetic profile and cause aberrant changes in brain growth, neuronal development, and functional connectivity. The past few years have seen an increase in the prevalence of ASD, as a result of enhanced clinical tests and diagnostic tools. Despite growing evidence for the involvement of endogenous biomarkers in the pathophysiology of ASD, early detection of this disorder remains a big challenge. This paper describes the main behavioral and cognitive features of ASD, as well as the symptoms that differentiate autism from other developmental disorders. An attempt will be made to integrate all the available evidence which point to reduced brain connectivity, mirror neurons deficits, and inhibition-excitation imbalance in individuals with ASD. Finally, this review discusses the main factors involved in the pathophysiology of ASD, and illustrates some of the most important markers used for the diagnosis of this debilitating disorder.

Concepts: Psychology, Developmental biology, Autism, Pervasive developmental disorder, Asperger syndrome, Autism spectrum, PDD-NOS, Neural development


Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children’s present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder.

Concepts: Antioxidant, Autism, Pervasive developmental disorder, Glutathione, Asperger syndrome, Autism spectrum, PDD-NOS, Cysteine


Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother-infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2 ) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (post-natal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one’s parents could be inherited in the following generation in a sex-dependent manner.


Lead (Pb) has become one of the most dangerous metals to human health, especially to the nervous system as its persistent accumulation and high toxicity. However, how the gut microbiota influence the Pb-related neurotoxicity remains unclear. The aim of our study was to explore the link among Pb exposure, behavior changes and gut microbiota.


Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular-junction-like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle.