Heat shock protein 27 rescues motor neurons following nerve injury and preserves muscle function

TY - JOUR

T1 - Heat shock protein 27 rescues motor neurons following nerve injury and preserves muscle function

AU - Sharp, Paul

AU - Krishnan, Michelle

AU - Pullar, Oliver

AU - Navarrete, Roberto

AU - Wells, Dominic

AU - de Belleroche, Jacqueline

PY - 2006/4

Y1 - 2006/4

N2 - Heat shock proteins (HSPs) are a family of ubiquitously expressed proteins that are up-regulated in response to a range of stresses and play an important role in cellular defence mechanisms. In previous studies, we demonstrated that overexpression of heat shock protein 27 (HSP27) in transgenic mice has significant cytoprotective properties in vivo, reducing caspase-3-mediated cell death in the hippocampus associated with limbic seizures and reducing infarct size in cardiac ischaemia. In motor neurons, HSP27 is also implicated as a survival promoting factor; however, it remains to be established whether HSP27 is able to exert long-term neuroprotective effects following neonatal nerve injury. We now show that, following neonatal nerve crush, HSP27 overexpression in vivo provides a substantial rescue of motor neurons 5–6 months following nerve injury. Furthermore, in vivo isometric tension recordings demonstrate that surviving motor neurons were able to regenerate, resulting in a 90% improvement (P < 0.0005) in motor unit number in HSP27 mice. Moreover, this increase in motor unit number was associated with improved muscle weight, muscle force, contractile speeds, and histochemical markers of muscle activity. These properties of HSP27 therefore have considerable potential for improving long-term muscle function in motor neuron disorders.

AB - Heat shock proteins (HSPs) are a family of ubiquitously expressed proteins that are up-regulated in response to a range of stresses and play an important role in cellular defence mechanisms. In previous studies, we demonstrated that overexpression of heat shock protein 27 (HSP27) in transgenic mice has significant cytoprotective properties in vivo, reducing caspase-3-mediated cell death in the hippocampus associated with limbic seizures and reducing infarct size in cardiac ischaemia. In motor neurons, HSP27 is also implicated as a survival promoting factor; however, it remains to be established whether HSP27 is able to exert long-term neuroprotective effects following neonatal nerve injury. We now show that, following neonatal nerve crush, HSP27 overexpression in vivo provides a substantial rescue of motor neurons 5–6 months following nerve injury. Furthermore, in vivo isometric tension recordings demonstrate that surviving motor neurons were able to regenerate, resulting in a 90% improvement (P < 0.0005) in motor unit number in HSP27 mice. Moreover, this increase in motor unit number was associated with improved muscle weight, muscle force, contractile speeds, and histochemical markers of muscle activity. These properties of HSP27 therefore have considerable potential for improving long-term muscle function in motor neuron disorders.

KW - Animals

KW - Animals, Newborn

KW - Choline O-Acetyltransferase

KW - Disease Models, Animal

KW - Dose-Response Relationship, Radiation

KW - Electric Stimulation

KW - Female

KW - HSP27 Heat-Shock Proteins

KW - Heat-Shock Proteins

KW - Immunohistochemistry

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Motor Neurons

KW - Muscle Contraction

KW - Muscle Fibers, Skeletal

KW - Muscle, Skeletal

KW - Nerve Crush

KW - Reaction Time

KW - Recovery of Function

KW - Sciatic Neuropathy

U2 - 10.1016/j.expneurol.2005.12.031

DO - 10.1016/j.expneurol.2005.12.031

M3 - Article

C2 - 16497297

SN - 0014-4886

VL - 198

SP - 511

EP - 518

JO - Experimental Neurology

JF - Experimental Neurology

IS - 2

M1 - N/A

ER -