Thermal preconditioning and heat-shock protein 72 preserve synaptic transmission during thermal stress.
As with other tissues, exposing the mammalian CNS to nonlethal heat stress (i.e., thermal preconditioning) increases levels of heat-shock proteins (Hsps) such as Hsp70 and enhances the viability of neurons under subsequent stress. Using a medullary slice preparation from a neonatal mouse, including the site of the neural network that generates respiratory rhythm (the pre-Bötzinger complex), we show that thermal preconditioning has an additional fundamental effect, protection of synaptic function. Relative to 30 degrees C baseline, initial thermal stress (40 degrees C) greatly increased the frequency of synaptic currents recorded without pharmacological manipulation by approximately 17-fold (p < 0.01) and of miniature postsynaptic currents (mPSCs) elicited by GABA (20-fold) glutamate (10-fold), and glycine (36-fold). Thermal preconditioning (15 min at 40 degrees C) eliminated the increase in frequency of overall synaptic transmission during acute thermal stress and greatly attenuated the frequency increases of GABAergic, glutamatergic, and glycinergic mPSCs (for each, p < 0.05). Moreover, without thermal preconditioning, incubation of slices in solution containing inducible Hsp70 (Hsp72) mimicked the effect of thermal preconditioning on the stress-induced release of neurotransmitter. That preconditioning and exogenous Hsp72 can affect and preserve normal physiological function has important therapeutic implications.
Kelty
Jonathan D
JD
Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, Illinois 60637, USA. j-kelty@uchicago.edu
Noseworthy
Peter A
PA
Feder
Martin E
ME
Robertson
R Meldrum
RM
Ramirez
Jan-Marino
JM
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005260:Female; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000494:pharmacology*; D018869:Heat-Shock Response / Q000502:physiology*; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D012125:Respiratory Center / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494372:Hspa8 protein, mouse; D011994:Recombinant Proteins