How does alcohol impair neuronal migration?

Kumada, Tatsuro; Jiang, Yulan; Cameron, D. Bryant; Komuro, Hitoshi

doi:10.1002/jnr.21149

Cited by 58 publications

(50 citation statements)

References 49 publications

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“…6A), this mechanism can be ruled out. Some studies have found increased cAMP levels or PKA activity in FAS (45,46); this would lead to an increased calcium current (41), so this mechanism can also be ruled out in our model because a reduction of the calcium current was observed. The activity of G proteins appears unchanged in FAS (47).…”

Section: Discussionmentioning

confidence: 87%

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Servais

Hourez²,

Bearzatto³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

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In cerebellum and other brain regions, neuronal cell death because of ethanol consumption by the mother is thought to be the leading cause of neurological deficits in the offspring. However, little is known about how surviving cells function. We studied cerebellar Purkinje cells in vivo and in vitro to determine whether function of these cells was altered after prenatal ethanol exposure. We observed that Purkinje cells that were prenatally exposed to ethanol presented decreased voltage-gated calcium currents because of a decreased expression of the ␥-isoform of protein kinase C. Longterm depression at the parallel fiber-Purkinje cell synapse in the cerebellum was converted into long-term potentiation. This likely explains the dramatic increase in Purkinje cell firing and the rapid oscillations of local field potential observed in alert fetal alcohol syndrome mice. Our data strongly suggest that reversal of longterm synaptic plasticity and increased firing rates of Purkinje cells in vivo are major contributors to the ataxia and motor learning deficits observed in fetal alcohol syndrome. Our results show that calcium-related neuronal dysfunction is central to the pathogenesis of the neurological manifestations of fetal alcohol syndrome and suggest new methods for treatment of this disorder.calcium ͉ cerebellum ͉ protein kinase ͉ long-term depression ͉ motor learning F etal alcohol syndrome (FAS) is the leading cause of intellectual disability in the Western world with a prevalence of 1 to 1.5 cases per 1,000 live births (1) and a lifetime cost of care of approximately $1.4 million per case. This cost is mainly because of ethanol toxicity in the developing central nervous system, causing intellectual disability, deficits in learning, and fine-motor dysfunction (2).The cerebellum is one of the main targets of in utero ethanol toxicity (3). Within the cerebellum, Purkinje cells (PCs) are highly sensitive to ethanol. PCs constitute the sole output of the cerebellar cortex and thus have a central functional role in integration. All animal models of FAS display a reduction in the number of PCs by Ϸ20% (4), and various authors have proposed that neuronal loss is the only cause of cerebellar deficits in FAS. One study conducted on adult anesthetized rats with FAS led to the conclusion that PCs that survive ethanol administration function normally (5). Thomas et al. (6) found a correlation between total PCs number and motor performance. These experimental data led to the assumption that surviving PCs function normally and that motor coordination impairment in FAS results only from a quantitative defect of PCs. This is crucially important from a therapeutic point of view because very few options exist to replace dead neurons. Many studies have therefore focused on different ways to decrease PC loss in FAS (7,8). However, different models of ataxia that result from PC death per se (pcd mice, SV4 mice, T147 transgenic mice) have demonstrated that considerable neuropathology can occur without the manifestation of a neurologic...

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Section: Discussionmentioning

confidence: 87%

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Servais

Hourez²,

Bearzatto³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

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“…This information is consistent with the fi ndings of Coriale et al 3 Impairments of verbal and non-verbal intelligence in the exposed samples were presented in several studies. 13,20,25,37,41,42 The verbal and non-verbal IQ were equally impaired 38,39 and with an undefi ned consistent pattern. 36 A study by Nash et al 32 also highlighted this diffi culty in both areas and the same study also emphasized that impairment in the verbal domain becomes increasingly pronounced with advancing age.…”

Section: General Intelligencementioning

confidence: 97%

Untitled

2017

JPTCP

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“…However, a hint of the relevance of alterations in calcium signalling in cortical pathologies linked to impaired neuronal migration emerges not from genetic mutations, but from environmental perturbations: Kumada et al [99] have shown that foetal alcohol syndrome (FAS), a serious disorder of brain development caused by maternal alcohol abuse during pregnancy, and other related disturbances, are linked to reduced calcium transients frequency and migratory activity of cerebellar granule cells; caffeine (1mM), by stimulating release form intracellular stores, and NMDA (30 µM), by inducing Ca 2+ influx, significantly reduced the effects of ethanol (25-100 mM) on the Ca 2+ transients and on migration. Similar effects were observed following inhibition of the cAMP pathway.…”

Section: Calcium Signalling and Neuronal Migration Disordersmentioning

confidence: 99%

Calcium Signaling in Neuronal Motility: Pharmacological Tools for Investigating Specific Pathways

Lovisolo

Ariano²,

Distasi³

2012

CMC

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Migration of neurons and neuronal precursors from the site of origin to their final location is a key process in the development of the nervous system and in the correct organization of neuronal structures and circuits. Different modes of migration (mainly radial and tangential) have been described in the last 40 years; for these, as for motility processes involving other cellular types, calcium signalling plays a key role, with influx from the extracellular medium representing the main mechanism, and a more delimited but specific role played by release from intracellular stores.Deciphering the involvement of the different calcium influx pathways has been a major task for cellular neurobiologists, and the availability -or lack -of reliable and selective pharmacological tools has represented the main limiting factor. This review addresses the strategies employed to investigate the role of voltage-dependent calcium channels and of neurotransmitter activated channels, either calcium permeable or not, that directly or indirectly can elicit cytosolic calcium increases; in addition, reference to recent findings on the involvement of other families of calcium permeable channels (such as the transient receptor potential superfamily) is presented. Finally, a brief description of the present -and limited -knowledge of the perturbations of calcium signalling involved in neuronal migration pathologies is provided.

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How does alcohol impair neuronal migration?

Cited by 58 publications

References 49 publications

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Untitled

Calcium Signaling in Neuronal Motility: Pharmacological Tools for Investigating Specific Pathways

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