Abstract
An immobilization stress (IS) of 1 h applied at the beginning of the dark phase is followed by a sleep rebound. During the restraint, serotonin released by the dorsal raphe nucleus within the arcuate area stimulates the availability of corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39). Three hours after the restraint, CLIP, through its hypnogenic properties, contributes to the sleep rebound that follows the IS. Here, we immunohistochemically evaluated protein expression of the immediate early gene, c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in hypothalamic (preoptic area [POA], paraventricular nucleus [PVN], arcuate nucleus [ARC]) and brain stem (dorsal raphe [DR], locus coeruleus [LC]) nuclei involved in the acute response to stress and the subsequent stress-related sleep rebound (recovery period). Immediately after the 1-h restraint, c-Fos and p-ERK expression increased in all structures studied, particularly in PVN and LC. Three hours later, the number of p-ERK- and c-Fos-positive neurons was reduced in PVN and LC (p < 0.001) as well as in DR (p < 0.01) compared to control animals. In contrast, both c-Fos and p-ERK expression in POA neurons (p < 0.01) and c-Fos expression in ARC neurons (p < 0.001) were increased 3 h after the IS. The marked activation observed in PVN and LC nucleus immediately after the IS confirms that these structures are clearly reactive to stress. However, the high activity observed in POA and ARC neurons during the recovery period, not described to date, highlights the particular part played by these structures in the stress-related sleep rebound. An unbalance in the above processes may contribute to pathological outcomes, such as anxiety and depression.
Similar content being viewed by others
References
Bonnet C, Leger L, Baubet V, Debilly G, Cespuglio R (1997) Influence of a 1 h immobilization stress on sleep states and corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39, Ph-ACTH18-39) brain contents in the rat. Brain Res 751:54–63
Briski K, Gillen E (2001) Differential distribution of Fos expression within the male rat preoptic area and hypothalamus in response to physical vs. psychological stress. Brain Res Bull 55:401–408
Carrasco GA, Van de Kar LD (2003) Neuroendocrine pharmacology of stress. Eur J Pharmacol 463:235–272
Cespuglio R, Marinesco S, Baubet V, Bonnet C, el Kafi B (1995) Evidence for a sleep-promoting influence of stress. Adv Neuroimmunol 5:145–154
Chowdhury GM, Fujioka T, Nakamura S (2000) Induction and adaptation of Fos expression in the rat brain by two types of acute restraint stress. Brain Res Bull 52:171–182
Cirelli C, Tononi G (2000a) On the functional significance of c-Fos induction during the sleep–waking cycle. Sleep 23:453–469
Cirelli C, Tononi G (2000b) Gene expression in the brain across the sleep–waking cycle. Brain Res 885:303–321
Cirelli C, Pompeiano M, Tononi G (1996) Neuronal gene expression in the waking state: a role for the locus coeruleus. Science 274:1211–1215
Dentico D, Amici R, Baracchi F, Cerri M, Del Sindaco E, Luppi M, Martelli D, Perez E, Zamboni G (2009) c-Fos expression in preoptic nuclei as a marker of sleep rebound in the rat. Eur J Neurosci 30:651–661
Descamps A, Cespuglio R (2010) Influence of aging on the sleep rebound induced by immobilization stress in the rat. Brain Res 1335:14–23
Diaz-Ruiz O, Navarro L, Mendez-Diaz M, Galicia O, Elder JH, Sanna PP, Drucker-Colin R, Prospero-Garcia O (2001) Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase. Brain Res 913:78–81
Garcia-Garcia F, Beltran-Parrazal L, Jimenez-Anguiano A, Vega-Gonzalez A, Drucker-Colin R (1998) Manipulations during forced wakefulness have differential impact on sleep architecture, EEG power spectrum, and Fos induction. Brain Res Bull 47:317–324
Gonzalez MM, Debilly G, Valatx JL, Jouvet M (1995) Sleep increase after immobilization stress: role of the noradrenergic locus coeruleus system in the rat. Neurosci Lett 202:5–8
Grewal SS, York RD, Stork PJ (1999) Extracellular-signal-regulated kinase signalling in neurons. Curr Opin Neurobiol 9:544–553
Gvilia I, Xu F, McGinty D, Szymusiak R (2006a) Homeostatic regulation of sleep: a role for preoptic area neurons. J Neurosci 26:9426–9433
Gvilia I, Turner A, McGinty D, Szymusiak R (2006b) Preoptic area neurons and the homeostatic regulation of rapid eye movement sleep. J Neurosci 26:3037–3044
Hegde P, Singh K, Chaplot S, Shankaranarayana Rao BS, Chattarji S, Kutty BM, Laxmi TR (2008) Stress-induced changes in sleep and associated neuronal activity in rat hippocampus and amygdala. Neuroscience 153:20–30
Imbe H, Murakami S, Okamoto K, Iwai-Liao Y, Senba E (2004) The effects of acute and chronic restraint stress on activation of ERK in the rostral ventromedial medulla and locus coeruleus. Pain 112:361–371
Koehl M, Bouyer JJ, Darnaudery M, Le Moal M, Mayo W (2002) The effect of restraint stress on paradoxical sleep is influenced by the circadian cycle. Brain Res 937:45–50
Kwon MS, Seo YJ, Shim EJ, Choi SS, Lee JY, Suh HW (2006) The effect of single or repeated restraint stress on several signal molecules in paraventricular nucleus, arcuate nucleus and locus coeruleus. Neuroscience 142:1281–1292
Leger L, Goutagny R, Sapin E, Salvert D, Fort P, Luppi PH (2009) Noradrenergic neurons expressing Fos during waking and paradoxical sleep deprivation in the rat. J Chem Neuroana 37:149–157
Lu J, Bjorkum AA, Xu M, Gaus SE, Shiromani PJ, Saper CB (2002) Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep. J Neurosci 22:4568–4576
Maloney KJ, Mainville L, Jones BE (1999) Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. J Neurosci 19(8):3057–3072
Marinesco S, Bonnet C, Cespuglio R (1999) Influence of stress duration on the sleep rebound induced by immobilization in the rat: a possible role for corticosterone. Neuroscience 92:921–933
Mercier S (2003) Behavioural changes after an acute stress: stressor and test type influences. Behav Brain Res 139:167–175
Palkovits M (2008) Stress-induced activation of neurons in the ventromedial arcuate nucleus: a blood–brain–CSF interface of the hypothalamus. Stress, Neurotransmitters, and Hormones. Ann N Y Acad Sci 1148:57–63
Papale LA, Andersen ML, Antunes IB, Alvarenga TA, Tufik S (2005) Sleep pattern in rats under different stress modalities. Brain Res 1060:47–54
Pawlyk AC, Morrison AR, Ross RJ, Brennan FX (2008) Stress-induced changes in sleep in rodents: models and mechanisms. Neurosci Biobehav Rev 32:99–117
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, San Diego
Pompeiano M, Cirelli C, Arrighi P, Tononi G (1995) c-Fos expression during wakefulness and sleep. Neurophysiol Clin 25:329–341
Ramos JW (2008) The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells. Int J Biochem Cell Biol 40:2707–2719
Rampin C, Cespuglio R, Chastrette N, Jouvet M (1991) Immobilisation stress induces a paradoxical sleep rebound in rat. Neurosci Lett 126:113–118
Rioja J, Santin LJ, Dona A, de Pablos L, Minano FJ, Gonzalez-Baron S, Aguirre JA (2006) 5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in serotonin neurons of the raphe nuclei after immobilization stress in the male rat. Neurosci Lett 397:190–195
Sasaguri K, Kikuchi M, Hori N, Yuyama N, Onozuka M, Sato S (2005) Suppression of stress immobilization-induced phosphorylation of ERK 1/2 by biting in the rat hypothalamic paraventricular nucleus. Neurosci Lett 383:160–164
Selye H (1950) Stress and the general adaptation syndrome. Br Med J 1:1383–1392
Senba E, Ueyama T (1997) Stress-induced expression of immediate early genes in the brain and peripheral organs of the rat. Neurosci Res 29:183–207
Shen CP, Tsimberg Y, Salvadore C, Meller E (2004) Activation of ERK and JNK MAPK pathways by acute swim stress in rat brain regions. BMC Neurosci 5:36
Shimizu Y, Sugama S, Degiorgio LA, Cho BP, Joh TH (2004) Cell-type specific signal transduction and gene regulation via mitogen-activated protein kinase pathway in catecholaminergic neurons by restraint stress. Neuroscience 129:831–839
Stamp J, Herbert J (2001) Corticosterone modulates autonomic responses and adaptation of central immediate-early gene expression to repeated restraint stress. Neuroscience 107:465–479
Suchecki D, Tiba PA, Machado RB (2012) REM sleep rebound as an adaptive response to stressful situations. Front Neurol 3(41):1–12
Sullivan NR, Crane JW, Damjanoska KJ, Carrasco GA, D’Souza DN, Garcia F, Van de Kar LD (2005) Tandospirone activates neuroendocrine and ERK (MAP kinase) signaling pathways specifically through 5-HT1A receptor mechanisms in vivo. Naunyn Schmiedebergs Arch Pharmacol 371:18–26
Tononi G, Cirelli C (2001) Modulation of brain gene expression during sleep and wakefulness: a review of recent findings. Neuropsychopharmacology 25:S28–S35
Van Reeth O, Weibel L, Spiegel K, Leproult R, Dugovic C, Maccari S (2000) Interactions between stress and sleep: from basic research to clinical situations. Sleep Med Rev 4:201–219
Vanhoutte P, Barnier JV, Guibert B, Pages C, Besson MJ, Hipskind RA, Caboche J (1999) Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices. Mol Cell Biol 19:136–146
Vazquez-Palacios G, Velazquez-Moctezuma J (2000) Effect of electric foot shocks, immobilization, and corticosterone administration on the sleep–wake pattern in the rat. Physiol Behav 71:23–28
Vazquez-Palacios G, Retana-Marquez S, Bonilla-Jaime H, Velazquez-Moctezuma J (2004) Stress-induced REM sleep increase is antagonized by naltrexone in rats. Psychopharmacology 171:186–190
Weinberg MS, Girotti M, Spencer RL (2007) Restraint-induced fra-2 and c-fos expression in the rat forebrain: relationship to stress duration. Neuroscience 150(2):478–486
Xia Z, Dudek H, Miranti CK, Greenberg ME (1996) Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism. J Neurosci 16:5
Acknowledgments
Financial support was provided by Claude Bernard University of Lyon, the Neuroscience Research Center of Lyon, Lyon, France, and Neuroscience Research Center, Shahid Beheshti Medical Sciences University, Evin, Teheran, Iran. The authors are also thankful to English Manager Science Editing (Sydney, Australia) for reviewing the English form.
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding authors
Additional information
G. Bezhadi and R. Cespuglio share equality for the last position.
Rights and permissions
About this article
Cite this article
Keshavarzy, F., Bonnet, C., Bezhadi, G. et al. Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound. Brain Struct Funct 220, 1793–1804 (2015). https://doi.org/10.1007/s00429-014-0728-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-014-0728-6