Prevention by Regular Exercise of Acute Sleep Deprivation-Induced Impairment of Late Phase LTP and Related Signaling Molecules in the Dentate Gyrus

Mol Neurobiol. 2016 Jul;53(5):2900-2910. doi: 10.1007/s12035-015-9176-4. Epub 2015 Apr 23.

Abstract

The dentate gyrus (DG) and CA1 regions of the hippocampus are intimately related physically and functionally, yet they react differently to insults. The purpose of this study was to determine the protective effects of regular treadmill exercise on late phase long-term potentiation (L-LTP) and its signaling cascade in the DG region of the hippocampus of rapid eye movement (REM) sleep-deprived rats. Adult Wistar rats ran on treadmills for 4 weeks then were acutely sleep deprived for 24 h using the modified multiple platform method. After sleep deprivation, the rats were anesthetized and L-LTP was induced in the DG region. Extracellular field potentials from the DG were recorded in vivo, and levels of L-LTP-related signaling proteins were assessed both before and after L-LTP expression using immunoblot analysis. Sleep deprivation reduced the basal levels of phosphorylated cAMP response element-binding protein (P-CREB) as well as other upstream modulators including calcium/calmodulin kinase IV (CaMKIV) and brain-derived neurotrophic factor (BDNF) in the DG of the hippocampus. Regular exercise prevented impairment of the basal levels of P-CREB and total CREB as well as those of CaMKIV in sleep-deprived animals. Furthermore, regular exercise prevented sleep deprivation-induced inhibition of L-LTP and post-L-LTP downregulation of P-CREB and BDNF levels in the DG. The current findings show that our exercise regimen prevents sleep deprivation-induced deficits in L-LTP as well as the basal and poststimulation levels of key signaling molecules.

Keywords: BDNF; CREB; DG; L-LTP; Sleep deprivation; Treadmill exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4 / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dentate Gyrus / metabolism*
  • Dentate Gyrus / physiopathology*
  • Long-Term Potentiation*
  • Male
  • Phosphorylation
  • Physical Conditioning, Animal*
  • Rats, Wistar
  • Signal Transduction*
  • Sleep Deprivation / physiopathology*
  • Sleep Deprivation / prevention & control*

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4