Suppression of hippocampal plasticity‐related gene expression by sleep deprivation in rats

Abstract

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.

The impact of sleep loss on hippocampal function

“…Taishi et al (2001) found that after 8 h of sleep deprivation the immediate early gene Arc increased within the hippocampus, but the growth factor BDNF remained unchanged. However, Guzman-Marin et al (2006) gene expression were reduced after sleep deprivation. Our group has recently examined gene-expression changes specifically within the hippocampus after sleep deprivation using genome-wide microarray assays.…”

A review of lifestyle factors that contribute to important pathways associated with major depression: Diet, sleep and exercise

“…Experimental studies show that prolonged sleep restriction or disruption affects hippocampal integrity (Guzman-Marin et al, 2006, Kopp et al, 2006, McDermott et al, 2003, Roman et al, 2005a. For example, in young male rats, one month of chronic sleep restriction reduced dorsal hippocampal volume by 10% (Novati et al, 2011).…”

Administration of the protein synthesis inhibitor, anisomycin, has distinct sleep-promoting effects in lateral preoptic and perifornical hypothalamic sites in rats

“…We interpret our finding as showing that the effects of PSI on sleep are mediated specifically by sleep-regulatory sites. Although PSI application in HIPPO is likely to affect local protein synthesis and hippocampal function, and sleep may facilitate synthesis of plasticity-related proteins such as brain derived neurotrophic factor (BDNF) in HIPPO (Guzman-Marin et al, 2006), our findings suggest that these interactions are not critically related to the control of sleep-wake states.…”

“…We have found that 48 h sleep deprivation reduces protein levels of brain-derived neurotrophic factor in hippocampus (Guzman-Marin et al, 2006).…”