Article abstract
Nature Neuroscience 11, 1294 - 1301 (2008)
Published online: 19 October 2008 | doi:10.1038/nn.2210
Focal transplantation–based astrocyte replacement is neuroprotective in a model of motor neuron disease
Angelo C Lepore1, Britta Rauck1, Christine Dejea1, Andrea C Pardo1, Mahendra S Rao2, Jeffrey D Rothstein1,3 & Nicholas J Maragakis1
Abstract
Cellular abnormalities in amyotrophic lateral sclerosis (ALS) are not limited to motor neurons. Astrocyte dysfunction also occurs in human ALS and transgenic rodents expressing mutant human SOD1 protein (SOD1G93A). Here we investigated focal enrichment of normal astrocytes using transplantation of lineage-restricted astrocyte precursors, called glial-restricted precursors (GRPs). We transplanted GRPs around cervical spinal cord respiratory motor neuron pools, the principal cells whose dysfunction precipitates death in ALS. GRPs survived in diseased tissue, differentiated efficiently into astrocytes and reduced microgliosis in the cervical spinal cords of SOD1G93A rats. GRPs also extended survival and disease duration, attenuated motor neuron loss and slowed declines in forelimb motor and respiratory physiological functions. Neuroprotection was mediated in part by the primary astrocyte glutamate transporter GLT1. These findings indicate the feasibility and efficacy of transplantation-based astrocyte replacement and show that targeted multisegmental cell delivery to the cervical spinal cord is a promising therapeutic strategy for slowing focal motor neuron loss associated with ALS.
- Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-119, Baltimore, Maryland 21287, USA.
- Invitrogen Corporation, 1610 Faraday Avenue, Carlsbad, California, USA.
- Department of Neuroscience, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Meyer 6-109, Baltimore, Maryland 21287, USA.
Correspondence to: Nicholas J Maragakis1 e-mail: nmaragak@jhmi.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Has gene therapy for ALS arrived?Nature Medicine News and Views (01 Oct 2003)
VEGF: multitasking in ALSNature Neuroscience News and Views (01 Jan 2005)
See all 6 matches for News And ViewsRESEARCH
Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALSNature Neuroscience Article (01 Jan 2005)
Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytesNature Biotechnology Research (01 Jan 2009)
See all 57 matches for Research
