The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels

Boulay, Anne; Saubaméa, Bruno; Cisternino, Salvatore; Mignon, Virginie; Mazeraud, Aurélien; Jourdren, Laurent; Blugeon, Corinne; Cohen-Salmon, Martine

doi:10.3389/fncel.2015.00009

Cited by 47 publications

(43 citation statements)

References 51 publications

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“…As opposed to more severe treatments used in previous studies (Eklind et al, 2001; Murray et al, 2015), the degree of severity of hypoxia and systemic inflammation used in the present work was moderate. Mild treatments applied elsewhere still led to brain inflammation associated with necrosis in young animals (Brochu et al, 2011), a loss of pericytes within the developing cortex in mice (Zehendner et al, 2013b), or to a blood-brain barrier breakdown (Zehendner et al, 2013a), but with less severe consequences.…”

Section: Discussioncontrasting

confidence: 59%

Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex

Mordel

Sheikh

Tsohataridis

et al. 2016

Neurobiology of Disease

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During the perinatal period, the brain is highly vulnerable to hypoxia and inflammation, which often cause white matter injury and long-term neuronal dysfunction such as motor and cognitive deficits or epileptic seizures. We studied the effects of moderate hypoxia (HYPO), mild systemic inflammation (INFL), or the combination of both (HYPO+INFL) in mouse somatosensory cortex induced during the first postnatal week on network activity and compared it to activity in SHAM control animals. By performing in vitro electrophysiological recordings with multi-electrode arrays from slices prepared directly after injury (P8–10), one week after injury (P13–16), or in young adults (P28–30), we investigated how the neocortical network developed following these insults. No significant difference was observed between the four groups in an extracellular solution close to physiological conditions. In extracellular 8 mM potassium solution, slices from the HYPO, INFL, and HYPO+INFL group were more excitable than SHAM at P8–10 and P13–16. In these two age groups, the number and frequency of spontaneous epileptiform events were significantly increased compared to SHAM. The frequency of epileptiform events was significantly reduced by the NMDA antagonist D-APV in HYPO, INFL, and HYPO+INFL, but not in SHAM, indicating a contribution of NMDA receptors to this pathophysiological activity. In addition, the AMPA/kainate receptor antagonist CNQX suppressed the remaining epileptiform activity. Electrical stimulation evoked prominent epileptiform activity in slices from HYPO, INFL and HYPO+INFL animals. Stimulation threshold to elicit epileptiform events was lower in these groups than in SHAM. Evoked events spread over larger areas and lasted longer in treated animals than in SHAM. In addition, the evoked epileptiform activity was reduced in the older (P28–30) group indicating that cortical dysfunction induced by hypoxia and inflammation was transient and compensated during early development.

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Section: Discussioncontrasting

confidence: 59%

Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex

Mordel

Sheikh

Tsohataridis

et al. 2016

Neurobiology of Disease

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“…The developmental window of rapid synapse formation and network connectivity in the first few years of life may perhaps be the best time to deliver a beneficial treatment 23,25,29 . The first 5 years of life is also a time of low serotonin production in the frontal cortex in children with ASD 51,52 .…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome

Hess

Fitzpatrick

Nguyen

et al. 2016

J Dev Behav Pediatr

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Objective Observational studies and anecdotal reports suggest sertraline, a selective serotonin reuptake inhibitor (SSRI), may improve language development in young children with fragile X syndrome (FXS). We evaluated the efficacy of six months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS ages 2–6 years. Results Eighty-one subjects were screened for eligibility and 57 were randomized to sertraline (27) or placebo (30). Two subjects from the sertraline arm and three from the placebo arm discontinued. Intent-to-treat analysis showed no difference from placebo on the primary outcomes: the Mullen Scales of Early Learning (MSEL) expressive language age equivalent and Clinical Global Impression-Improvement (CGI-I). However, analyses of secondary measures showed significant improvements, particularly in motor and visual perceptual abilities and social participation. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events occurred. Conclusion This randomized controlled trial of six-months of sertraline treatment showed no primary benefit with respect to early expressive language development and global clinical improvement. However, in secondary, exploratory analyses there were significant improvements seen on motor and visual perceptual subtests, the Cognitive T score sum on the MSEL, and on one measure of Social Participation on the Sensory Processing Measure–Preschool. Further, post hoc analysis found significant improvement in early expressive language development as measured by the MSEL among children with ASD on sertraline. Treatment appears safe for this 6-month period in young children with FXS, but we do not know the long-term side effects of this treatment. These results warrant further studies of sertraline in young children with FXS using refined outcome measures, as well as longer term follow-up studies to address long-term side effects of low-dose sertraline in early childhood.

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“…Postnatal glia cultures were prepared as previously described [35]. Glia media (10% FBS, 2 mM glutamine, 1X penicillin/streptomycin in EMEM) was changed each week.…”

Section: Methodsmentioning

confidence: 99%

Iron Deficiency Impairs Developing Hippocampal Neuron Gene Expression, Energy Metabolism, and Dendrite Complexity

et al. 2016

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Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of the iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a degree of neuronal ID similar to that seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e. BdnfVI,Camk2a,Vamp1,Psd95,Cfl1, Pfn1,Pfn2, and Gda) and mitochondrial function (i.e. Ucp2,Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons were reduced. By 18DIV, partial recovery of the dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and the length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory.

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The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels

Cited by 47 publications

References 51 publications

Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex

Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex

A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome

Iron Deficiency Impairs Developing Hippocampal Neuron Gene Expression, Energy Metabolism, and Dendrite Complexity

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