Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats.

Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Research Abstract Details 

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Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Abstract Text:

The translocator protein (18 kDa; TSPO), formerly known as the peripheral benzodiazepine receptor, is an outer mitochondrial membrane protein that associates with the mitochondrial permeability transition pore to regulate both steroidogenesis and apoptosis. TSPO expression is induced in adult dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury and a TSPO receptor ligand, Ro5-4864, enhances DRG neurite growth in vitro and axonal regeneration in vivo. We have now found that TSPO is induced in neonatal motor neurons after peripheral nerve injury and have evaluated its involvement in neonatal and adult sensory and motor neuron survival, and in adult motor neuron regeneration. The TSPO ligand Ro5-4864 rescued cultured neonatal DRG neurons from nerve growth factor withdrawal-induced apoptosis and protected neonatal spinal cord motor neurons from death due to sciatic nerve axotomy. However, Ro5-4864 had only a small neuroprotective effect on adult facial motor neurons after axotomy, did not delay onset or prolong survival in SOD1 mutant mice, and failed to protect adult DRG neurons from sciatic nerve injury-induced death. In contrast, Ro5-4864 substantially enhanced adult facial motor neuron nerve regeneration and restoration of function after facial nerve axotomy. These data indicate a selective sensitivity of neonatal sensory and motor neurons to survival in response to Ro5-4864, which highlights that survival in injured immature neurons cannot necessarily predict success in adults. Furthermore, although Ro5-4864 is only a very weak promoter of survival in adult neurons, it significantly enhances regeneration and functional recovery in adults.

Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Publishing Authors By Initials

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Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The European journal of neuroscience

VOLUME: 27

Page Numbers: 937-46

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ISSN: 1460-9568

DAY: 12

MONTH: Feb

YEAR: 2008

Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats.

AFFILIATION: Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. cmills@neurocrine.com

Country: France

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MEDLINETA: Eur J Neurosci

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