BDNF-induced White Matter Neuroprotection and Stage-dependent Neuronal Survival Following a Neonatal Excitotoxic Challenge

Husson, Isabelle; Rangon, Claire-Marie; Lelièvre, Vincent; Bemelmans, Alexis-Pierre; Sachs, P.; Mallet, Jacques; Kosofsky, Barry E.; Gressèns, Pierre

doi:10.1093/cercor/bhh127

Cited by 105 publications

(67 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such studies have revealed that there are spiking and nonspiking OPCs and preOLs, and that the spiking class has a selective sensitivity to excitotoxicity in adult spinal cord injury (Karadottir et al, 2008). Overstimulating ionotropic glutamate receptors on preOLs specifically leads to preOL death in vitro (Follett et al, 2000;Husson et al, 2005;Manning et al, 2008). The GENSAT project (http://www.gensat.…”

Section: New Markers For Stage-specific Study Of the Oligodendrocyte mentioning

confidence: 99%

Towards improved animal models of neonatal white matter injury associated with cerebral palsy

Silbereis

Huang

Back

et al. 2010

Disease Models &Amp; Mechanisms

109

View full text Add to dashboard Cite

Newborn neurological injuries are the leading cause of intellectual and motor disabilities that are associated with cerebral palsy. Cerebral white matter injury is a common feature in hypoxic-ischemic encephalopathy (HIE), which affects fullterm infants, and in periventricular leukomalacia (PVL), which affects preterm infants. This article discusses recent efforts to model neonatal white matter injury using mammalian systems. We emphasize that a comprehensive understanding of oligodendrocyte development and physiology is crucial for obtaining new insights into the pathobiology of HIE and PVL as well as for the generation of more sophisticated and faithful animal models.

show abstract

Section: New Markers For Stage-specific Study Of the Oligodendrocyte mentioning

confidence: 99%

Towards improved animal models of neonatal white matter injury associated with cerebral palsy

Silbereis

Huang

Back

et al. 2010

Disease Models &Amp; Mechanisms

109

View full text Add to dashboard Cite

show abstract

“…For each sample, 600 ng were used in reverse transcription (iScript kit; Bio-Rad, Hercules, CA). As described previously (Husson et al, 2005), for the glucocorticoid receptor, the following pair of primers was designed to selectively amplify a 93 bp fragment spanning the 1234 -1336 region of the published mouse sequence (NR3C1, NM008173): 5Ј-TTATGGATATTCAAGCCCTGG-OH and 5ЈAGGCAGAGTTTGGGAGGTAGT-OH. To standardize the experiments, we used a primer set (5-CCGGCTTGTATGCTATC and 5-TCAGTATGTTCGGCTTC, as sense and antisense, respectively) for the mouse ␤2-microglobulin gene.…”

Section: Real-time Reverse Transcription-pcr For Glucocorticoid Recepmentioning

confidence: 99%

Chronic Mild Stress during Gestation Worsens Neonatal Brain Lesions in Mice

Rangon

Fortes²,

Lelièvre³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Cerebral palsy remains a public health priority. Recognition of factors of susceptibility to perinatal brain lesions is key for the prevention of cerebral palsy. In most cases, the pathophysiology of these lesions is thought to involve prior exposure to predisposing factors that make the developing brain more vulnerable to perinatal events. The present study tested the hypothesis that exposure to chronic minimal stress throughout gestation would sensitize the offspring to neonatal excitotoxic brain lesions, which mimic lesions observed in cerebral palsy. Pregnant mice were exposed to chronic, ultramild stress, applied throughout gestation. Neonatal brain lesions were induced by intracerebral injection of glutamate analogs. Excitotoxic lesions were significantly worsened in pups exposed to gestational stress. Stress induced a significant rise of circulating corticosterone levels both in pregnant mothers and in newborn pups. The deleterious effects of stress on excitotoxicity were totally suppressed in mice with reduced levels of glucocorticoid receptors. Stress induced a significant increase of neopallial NMDA binding sites in the offspring. At adulthood, animals exposed to stress and neonatal excitotoxic challenge showed a significant impairment in the Morris water maze test when compared with animals exposed to the excitotoxic challenge but not the gestational stress. These findings suggest that stress during gestation, which may mimic low-level stress in human pregnancy, could be a novel risk factor for cerebral palsy.

show abstract

“…21 GAP-43 is expressed along with BDNF in response to neuronal injuries and is upregulated in granule cells following BDNF treatment. 22,23 In the present study, we test whether GAP-43 is an essential downstream effector of positive AMPA receptor modulators and subsequent BDNF-induced responses.Results S18986 and BDNF enhance GAP-43 expression. In agreement with previous data, 9 there was a threefold increase in BDNF mRNA levels after 3 h of stimulation of…”

mentioning

confidence: 99%

mentioning

confidence: 99%

GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986

et al. 2009

View full text Add to dashboard Cite

Positive a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators include benzamide compounds that allosterically modulate AMPA glutamate receptors. These small molecules that cross the blood-brain barrier have been shown to act as a neuroprotectant by increasing the levels of endogenous brain-derived neurotrophic factor (BDNF). Positive AMPA receptor modulators have also been shown to increase the levels of growth-associated protein-43 (GAP-43). GAP-43 plays a major role in many aspects of neuronal function in vertebrates. The goal of this study was to determine whether GAP-43 was important in mediating the actions of positive AMPA receptor modulator (S18986) and BDNF. Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures; (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDNF; (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy. Positive a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators allosterically modulate AMPA-type glutamate receptors and facilitate fast excitatory transmission, 1,2 and have been shown to enhance learning and memory. [3][4][5] Positive AMPA receptor modulators also decrease neuronal loss in excitotoxic neonatal brain lesions. 6 Thus, positive AMPA receptor modulators are potential candidates for treatment of diseases characterized by cognitive dysfunction and neuronal loss. 7,8 Some of the effects of positive AMPA receptor modulators are mediated via increased BDNF expression. 9,10 Positive AMPA receptor modulators however are preferred over direct administration of BDNF itself as this class of molecules readily crosses the blood-brain barrier. 11 Brain-derived neurotrophic factor is important for appropriate development and connectivity of neurons as well as their survival. 12,13 In adults, activity dependent modulation of BDNF levels is important for synaptic plasticity and remodeling. 14,15 Activation of the extracellular-regulated kinases (ERKs) pathway by BDNF is important for neuronal survival. 16,17 BDNF mediates activity dependent synaptic plasticity by mechanisms that involve receptor regulation and localized gene transcription. 18,19 At present, it is unclear whether the neuroprotection, synaptic remodeling and plasticity effects of BDNF are related to each other through common downstream elements.Growth-associated protein-43 (GAP-43) is a nervous system specific F-actin regulating phosphoprotein expressed during de...

show abstract

BDNF-induced White Matter Neuroprotection and Stage-dependent Neuronal Survival Following a Neonatal Excitotoxic Challenge

Cited by 105 publications

References 36 publications

Towards improved animal models of neonatal white matter injury associated with cerebral palsy

Towards improved animal models of neonatal white matter injury associated with cerebral palsy

Chronic Mild Stress during Gestation Worsens Neonatal Brain Lesions in Mice

GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986

Contact Info

Product

Resources

About