Gene expression in the rat cerebral cortex: Comparison of recovery sleep and hypnotic-induced sleep

• Published in: Neuroscience 2006-01, Vol.141 (1), p.371-378
• Main Authors: Wisor, J.P., Morairty, S.R., Huynh, N.T., Steininger, T.L., Kilduff, T.S.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Cerebral Cortex - metabolism; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Electroencephalography - methods; Fos-Related Antigen-2 - genetics; Fos-Related Antigen-2 - metabolism; Fundamental and applied biological sciences. Psychology; gamma-hydroxybutyrate; Gene Expression - physiology; glucose-regulated proteins; heat shock proteins; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Hypnotics and Sedatives - pharmacology; immediate early genes; Male; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system (semeiology, syndromes); Neurology; Nuclear Receptor Subfamily 4, Group A, Member 1; Rats; Rats, Inbred WKY; Reaction Time - drug effects; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; Recovery of Function - drug effects; Recovery of Function - physiology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Sleep - drug effects; Sleep - physiology; Sleep deprivation; Sleep Deprivation - physiopathology; Sleep. Vigilance; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrates: nervous system and sense organs; zolpidem
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.03.028

Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABAB ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the ω1 site on the GABAA receptor/Cl− ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.