TY - JOUR T1 - Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9735 LP - 9745 DO - 10.1523/JNEUROSCI.1912-05.2005 VL - 25 IS - 42 AU - Mac B. Robinson AU - J. Lille Tidwell AU - Thomas Gould AU - Anna R. Taylor AU - Jason M. Newbern AU - Jason Graves AU - Michael Tytell AU - Carol E. Milligan Y1 - 2005/10/19 UR - http://www.jneurosci.org/content/25/42/9735.abstract N2 - The dependence of developing spinal motoneuron survival on a soluble factor(s) from their target, muscle tissue is well established both in vivo and in vitro. Considering this apparent dependence, we examined whether a specific component of the stress response mediates motoneuron survival in trophic factor-deprived environments. We demonstrate that, although endogenous expression of heat shock protein 70 (HSP70) did not change during trophic factor deprivation, application of e-rhHsp70 (exogenous recombinant human Hsp70) promoted motoneuron survival. Conversely, depletion of HSP70 from chick muscle extract (MEx) potently reduces the survival-promoting activity of MEx. Additionally, exogenous treatment with or spinal cord overexpression of Hsp70 enhances motoneuron survival in vivo during the period of naturally occurring cell death [programmed cell death (PCD)]. Hindlimb muscle cells and lumbar spinal astrocytes readily secrete HSP70 in vitro, suggesting potential physiological sources of extracellular Hsp70 for motoneurons. However, in contrast to exogenous treatment with or overexpression of Hsp70 in vivo, muscle-targeted injections of this factor in an ex vivo preparation fail to attenuate motoneuron PCD. These data (1) suggest that motoneuron survival requirements may extend beyond classical trophic factors to include HSP70, (2) indicate that the source of this factor is instrumental in determining its trophic function, and (3) may therefore influence therapeutic strategies designed to increase motoneuron Hsp70 signaling during disease or injury. ER -