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Mephedrone, a synthetic derivative of cathinone, is a commonly used psychoactive substance. Our previous study showed that exposure to mephedrone during pegnancy induced antiproliferative and pro-apoptotic effects in hippocampus of mice delivered pups. However, its effects on neural stem/progenitor cells (NS/PC) remain unexplored. The aim of this study is to investigate the effects of mephedrone exposure on the proliferation, differentiation, and apoptosis of rat embryonic NS/PC. NS/PC were isolated from rat fetal ganglionic eminence region at embryonic day 14.5. The effects of mephedrone on cell proliferation, neurosphere formation (colonies of NS/PC), neuronal differentiation, and apoptosis of NS/PC were assessed using MTT, immunocytochemistry, and flow cytometry. Mephedrone at concentrations of 20-640 [micro]M significantly decreased the proliferation of NS/PC, induced cell cycle arrest, and enhanced the percent of apoptotic and necrotic cells. Neurosphere assays revealed a significant reduction in the number and diameter of neurosphere-forming cells. In addition, mephedrone significantly decreased the expressions of DCX and NeuN neuronal markers. Taken together, our results suggeste that exposure to mephedrone decreases the viability and neuronal differentiation of embryonic NS/PC. This study showed that mephedrone exposure during fetal or neonatal life may impair neurogenesis and subsequent brain development. Key words: differentiation, mephedrone, neural stem cells, neurotoxicity, proliferation, Introduction Mephedrone, 4-methylmethcathinone (4-MMC), belongs to the [beta]-ketoamphetamines family (Naserzadeh et al. 2019). It is usually abused to induce euphoria, increase mood, and other stimulating effects (Wood and Dargan 2012). [...]

Serotonin (5-HT) acts as a neuromodulator and plays a critical role in brain development. Changes in 5-HT signaling during the perinatal period can affect neural development and may result in behavioral changes in adulthood; however, further investigations are necessary including both sexes to study possible differences. Thus, the aim of this study was to investigate the impact of neonatal treatment with fluoxetine on the development of male and female offspring. The animals were divided into four groups according to sex and treatment. The experimental groups received fluoxetine at 10 mg * [kg.sup.-1] (1 [micro]L/g of body weight (bw)) and the animals of control group received saline solution 0.9% (1 [micro]L/g of bw) from postnatal days 1-21. In the neonatal period, reflex ontogeny, somatic development, physical features, and food intake were recorded. In the postnatal period (until day 31) bw and post-weaning food intake were recorded. Chronic administration of fluoxetine in the neonatal period caused a delay in the reflex ontogeny and somatic development, as well as reduction of lactation, post-weaning bw, and post-weaning food intake in rats. No difference was found between the sexes. These changes reaffirm that serotonin plays an important role in regulating the plasticity of the brain during the early development period, but without sex differences. Key words: serotonin, fluoxetine, reflex, growth and development, feeding behavior, sex difference. La serotonine (5-HT) agit comme neuromodulateur et joue un role crucial dans le developpement du cerveau. Des variations dans les voies de signalisation de la 5-HT au cours de la periode perinatale peuvent affecter le developpement neurologique et pourraient entrainer des changements comportementaux a l'age adulte. Cependant, plus de recherches sont necessaires, y compris des etudes portant sur des differences eventuelles entre les sexes. Par consequent, cette etude portait sur l'incidence de l'administration de fluoxetine au cours de la periode neonatale sur le developpement de rejetons males et femelles. Nous avons reparti les animaux dans quatre groupes selon le sexe et le traitement administre. Les groupes experimentaux ont recu de la fluoxetine a 10 mg/kg (1 [micro]l/g de masse corporelle) et les animaux du groupe temoin ont recu une solution saline a 0,9 % (1 [micro]l/g de masse corporelle) de 1 a 21 jours apres la naissance. Au cours de la periode neonatale, nous avons enregistre les parametres suivants: ontogenese des reflexes, developpement somatique, caracteristiques physiques et apport alimentaire. Au cours de la periode postnatale (jusqu'au jour 31) nous avons enregistre la masse corporelle et l'apport alimentaire apres le sevrage. L'administration prolongee de fluoxetine au cours de la periode neonatale a mene a un retard dans l'ontogenie des reflexes et le developpement somatique, une diminution de la masse corporelle avant et apres le sevrage, ainsi que de l'apport alimentaire apres le sevrage. Nous n'avons observe aucune difference entre les sexes. Ces variations reconfirment que la 5-HT joue un role important dans la regulation de la plasticite du cerveau au cours de la periode de developpement precoce, mais sans difference entre les sexes. Mots-cles: serotonine, fluoxetine, reflexe, croissance et developpement, comportements alimentaires, differences entre les sexes., 1. Introduction Serotonin (5-HT) is a widely distributed neuromodulator that plays an important role in regulating brain development (Gaspar et al. 2003). In early developmental periods, it acts as a [...]

Author(s): Yoon Kyung Choi (corresponding author) [1, 2]; Takakuni Maki [1, 2]; Emiri T Mandeville [1, 2]; Seong-Ho Koh [1, 2, 3]; Kazuhide Hayakawa [1, 2]; Ken Arai [1, 2]; [...]

Individuals with autism spectrum disorder (ASD) and their relatives process faces differently from typically developed (TD) individuals. In an fMRI face-viewing task, TD and undiagnosed sibling (SIB) children (5-18 years) showed face specialization in the right amygdala and ventromedial prefrontal cortex, with left fusiform and right amygdala face specialization increasing with age in TD subjects. SIBs showed extensive antero-medial temporal lobe activation for faces that was not present in any other group, suggesting a potential compensatory mechanism. In ASD, face specialization was minimal but increased with age in the right fusiform and decreased with age in the left amygdala, suggesting atypical development of a frontal-amygdala-fusiform system which is strongly linked to detecting salience and processing facial information., Author(s): Jane E. Joseph[sup.1] , Xun Zhu[sup.1] , Andrew Gundran[sup.1] , Faraday Davies[sup.1] , Jonathan D. Clark[sup.2] , Lisa Ruble[sup.3] , Paul Glaser[sup.2] [sup.4] , Ramesh S. Bhatt[sup.5] Author Affiliations: [...]

Author(s): Katherine Bourzac [1] [illus. 1] Two years after having a stroke at 31, Sonia Olea Coontz remained partially paralysed on her right side. She could barely move her arm, [...]

Injury stimulates neurogenesis in the adult brain, but the role of injury-induced neurogenesis in brain repair and recovery is uncertain. One strategy for investigating this issue is to ablate neuronal precursors and thereby prevent neurogenesis, but this is difficult to achieve in a specific fashion. We produced transgenic mice that express herpes simplex virus thymidine kinase (TK) under control of the promoter for doublecortin (Dcx), a microtubuleassociated protein expressed in newborn and migrating neurons. Treatment for 14 days with the antiviral drug ganciclovir (GCV) depleted Dcx-expressing and BrdU-labeled cells from the rostral subventricular zone and dentate gyrus, and abolished neurogenesis and associated neuromigration induced by focal cerebral ischemia. GCV treatment of Dcx-TK transgenic, but not WT, mice also increased infarct size and exacerbated postischemic sensorimotor behavioral deficits measured by rotarod, limb placing, and elevated body swing tests. These findings provide evidence that injuryinduced neurogenesis contributes to stroke outcome and might therefore be a target for stroke therapy. doi/ 10.1073/pnas.1000154107

The pathogenesis of Huntington's disease (HD) remains elusive. The identification of increasingly early pathophysiological abnormalities in HD suggests the possibility that impairments of striatal medium spiny neuron (MSN) specification and maturation may underlie the etiology of HD. In fact, we demonstrate that HD knock-in (Hdh-Q111) mice exhibited delayed acquisition of early striatal cytoarchitecture with aberrant expression of progressive markers of MSN neurogenesis (Islet1, DARPP-32, mGluR1, and NeuN). Hdh-Q111 striatal progenitors also displayed delayed cell cycle exit between E13.5-15.5 (BrdU birth-dating) and an enhanced fraction of abnormal cycling cells in association with expansion of the pool of intermediate progenitors and over expression of the core pluripotency (PP) factor, Sox2. Clonal analysis further revealed that Hdh-Q111 neural stem cells (NSCs) displayed: impaired lineage restriction, reduced proliferative potential, enhanced late-stage self-renewal, and deregulated MSN subtype specification. Further, our analysis revealed that in addition to Sox2, the core PP factor, Nanog is expressed within the striatal generative and mantle regions, and in Hdh-Q111 embryos the fraction of Nanog-expressing MSN precursors was substantially increased. Moreover, compared to Hdh-Q18 embryos, the Hdh-Q111 striatal anlagen exhibited significantly higher levels of the essential PP cofactor, Stat3. These findings suggest that Sox2 and Nanog may play roles during a selective window of embryonic brain maturation, and alterations of these factors may, in part, be responsible for mediating the aberrant program of Hdh-Q111 striatal MSN specification and maturation. We propose that these HD-associated developmental abnormalities might compromise neuronal homeostasis and subsequently render MSNs more vulnerable to late life stressors. development | huntingtin | medium spiny neurons | neurodegeneration doi/10.1073/pnas.0912171106