Premium
Suppression of hippocampal plasticity‐related gene expression by sleep deprivation in rats
Author(s) -
GuzmanMarin Ruben,
Ying Zhe,
Suntsova Natalia,
Methippara Melvi,
Bashir Tariq,
Szymusiak Ronald,
GomezPinilla Fernando,
McGinty Dennis
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.115287
Subject(s) - synapsin i , long term potentiation , hippocampal formation , endocrinology , creb , hippocampus , neocortex , medicine , sleep deprivation , brain derived neurotrophic factor , synaptic plasticity , neurotrophic factors , neuroscience , chemistry , biology , circadian rhythm , transcription factor , biochemistry , vesicle , receptor , membrane , gene , synaptic vesicle
Previous work shows that sleep deprivation impairs hippocampal‐dependent learning and long‐term potentiation (LTP). Brain‐derived neurotrophic factor (BDNF), cAMP response‐element‐binding (CREB) and calcium–calmodulin‐dependent protein kinase II (CAMKII) are critical modulators of hippocampal‐dependent learning and LTP. In the present study we compared the effects of short‐ (8 h) and intermediate‐term (48 h) sleep deprivation ( SD ) on the expression of BDNF and its downstream targets, Synapsin I, CREB and CAMKII in the neocortex and the hippocampus. Rats were sleep deprived using an intermittent treadmill system which equated total movement in the SD and control treadmill animals (CT), but permitted sustained periods of rest in CT animals. Animals were divided into SD (treadmill schedule: 3 s on/12 s off) and two treadmill control groups, CT1 (15 min on/60 min off) and CT2 (30 min on/120 min off – permitting more sustained sleep). Real‐time Taqman RT‐PCR was used to measure changes in mRNA; BDNF protein levels were determined using ELISA . In the hippocampus, 8 h treatments reduced BDNF , Synapsin I, CREB and CAMKII gene expression in both SD and control groups. Following 48 h of experimental procedures, the expression of all these four molecular markers of plasticity was reduced in SD and CT1 groups compared to the CT2 and cage control groups. In the hippocampus, BDNF protein levels after 8 h and 48 h treatments paralleled the changes in mRNA. In neocortex, neither 8 h nor 48 h SD or control treatments had significant effects on BDNF , Synapsin I and CAMKII mRNA levels. Stepwise regression analysis suggested that loss of REM sleep underlies the effects of SD on hippocampal BDNF , Synapsin I and CREB mRNA levels, whereas loss of NREM sleep underlies the effects on CAMKII mRNA.