Abstract
Mammalian torpor is associated with neuronal tau protein hyperphosphorylation. This process is fully reversed upon rewarming to euthermy. Not much is known about the hyperphosphorylation dynamics during cooling and rewarming to and from torpor. In this study we show that there is a negative relation between brain temperature and the amount of tau hyperphosphorylation in the cortex of Syrian hamsters. This relation was found to be nonlinear: the fastest changes in the hyperphosphorylation state of the tau protein occurred around brain temperatures of ~27°C. The amount of hyperphosphorylation did not substantially increase further with the time spent in torpor. In mice, reversible hyperphosphorylation could also be detected during torpor-like hypothermia at 21°C, but was not present during torpor-like hypothermia at an ambient temperature of 30°C. These results suggest that tau hyperphosphorylation is not only passively connected with brain temperature, but is actively regulated. The results argue against a need for periodic euthermy to reverse hyperphosphorylation of tau in the brain. Alternatively we hypothesise that the phosphorylation of the tau protein may play an active role in the regulation of the neuronal metabolism, facilitating the entrance and or maintenance of the torpid state.
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References
Arendt T, Stieler J, Strijkstra AM, Hut RA, Rudiger J, Van der Zee EA, Harkany T, Holzer M, Hartig W (2003) Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J Neurosci 23:6972–6981
Barnes BM (1989) Freeze avoidance in a mammal: body temperatures below 0 degree C in an Arctic hibernator. Science 244:1593–1595
Boerema AS (2012) The brain at low temperature: neuronal and behavioural dynamics in mammalian hibernation and torpor. PhD thesis, University of Groningen
Boerema AS, Steinlechner S, Van der Zee EA, Keijser JN, Stieler J, Strijkstra AM (2008) Reversible hyperphosphorylation of the microtubule-associated protein tau during daily torpordaily torpor in Djungarian hamsters. In: Lovegrove BG, McKechnie AE (eds) Hypometabolism in animals: hibernation, torpor and cryobiology. Pietermartizburg, South Africa, pp 151–156
van Breukelen F, Martin SL (2001) Translational initiation is uncoupled from elongation at 18 degrees C during mammalian hibernation. Am J Physiol Regul Integr Comp Physiol 281:R1374–R1379
van Breukelen F, Martin SL (2002) Reversible depression of transcription during hibernation. J. Comp. Physiol. B. Biochem Syst Environ Physiol 172:355–361
Carey HV, Andrews MT, Martin SL (2003) Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153–1181
Deboer T, Franken P, Tobler I (1994) Sleep and cortical temperature in the Djungarian hamster under baseline conditions and after sleep deprivation. J Comp Physiol A 174:145–155
Deboer T, Tobler I (1995) Temperature dependence of EEG frequencies during natural hypothermia. Brain Res 670:153–156
Gong C-X, Liu F, Grundke-Iqbal I, Iqbal K (2006) Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylationtau. J Alzheimers Dis 9:1–12
Hart GW (1997) Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. Annu Rev Biochem 66:315–335
Härtig W, Stieler JT, Boerema AS, Wolf J, Schmidt U, Weissfuss J, Bullmann T, Strijkstra AM, Arendt T (2007) Hibernation model of tau phosphorylation in hamsters: selective vulnerability of cholinergic basal forebrain neurons—implications for Alzheimer’s disease. Eur J Neurosci 25:69–80
Heldmaier G, Ortmann S, Elvert R (2004) Natural hypometabolism during hibernation and daily torpordaily torpor in mammals. Respir Physiol Neurobiol 141:317–329
Heldmaier G, Ruf T (1992) Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B Biochem Syst Environ Physiol 162:696–706
Hut RA, Pilorz V, Boerema AS, Strijkstra AM, Daan S (2011) Working for food shifts nocturnal mouse activity into the day. PLoS ONE 6:e17527
Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, Coxson PG, Budinger TF (1991) Diminished glucose transport in Alzheimer’s disease: dynamic PET studies. J Cereb Blood Flow Metab 11:323–330
Johnson GVW, Stoothoff WH (2004) Tau phosphorylation in neuronal cell function and dysfunction. J Cell Sci 117:5721–5729
Krilowicz BL, Glotzbach SF, Heller HC (1988) Neuronal activity during sleep and complete bouts of hibernation. Am J Physiol Regul Integr Comp Physiol 255:R1008–R1019
Lee Y-ja, S-ichi Miyake, Wakita H, McMullen DC, Azuma Y, Auh S, Hallenbeck JM (2007) Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells. J Cereb Blood Flow Metab 27:950–962
Liu F, Iqbal K, Grundke-Iqbal I, Hart GW, Gong C-X (2004) O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer’s disease. Proc Natl Acad Sci USA 101:10804–10809
Lyman CP (1948) The oxygen consumption and temperature regulation of hibernating hamsters. J Exp Zool 109:55–78
Lyman CP, O’Brien RC (1974) A comparison of temperature regulation in hibernating rodents. Am J Physiol 227:218–223
Nickerson DM, Facey DE, Grossman GD (1989) Estimating physiological thresholds with continuous two-phase regression. Physiol Zool 62:866–887
Planel E, Miyasaka T, Launey T, Chui D-H, Tanemura K, Sato S, Murayama O, Ishiguro K, Tatebayashi Y, Takashima A (2004) Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer’s disease. J Neurosci 24:2401–2411
Schubert KA, Boerema AS, Vaanholt LM, de Boer SF, Strijkstra AM, Daan S (2010) Daily torpor in mice: high foraging costs trigger energy-saving hypothermia. Biol Lett 6:132–135
Shafi R, Iyer SPN, Ellies LG, O’Donnell N, Marek KW, Chui D, Hart GW, Marth JD (2000) The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. Proc Nat Acad Sci 97:5735–5739
Stieler JT, Bullmann T, Kohl F, Tøien O, Brückner MK, Härtig W, Barnes BM, Arendt T (2011) The physiological link between metabolic rate depression and tau phosphorylation in mammalian hibernation. PLoS ONE 6:e14530
Storey KB (2010) Out cold: biochemical regulation of mammalian hibernation—a mini-review. Gerontology 56:220–230
Strijkstra AM (1999) Periodic euthermy during hibernation in the European ground squirrel: causes and consequences. PhD Thesis, University of Groningen
Strijkstra AM (2006) Good and bad in the hibernating brain. J British Interplanet Soc 59:119–123
Strijkstra AM (2009) Hibernation in Encyclopedia of neuroscience Berlin. Springer, Heidelberg, pp 1831–1836
Strijkstra AM, de Boer T, Daan S (2000) Slowing of sigma and theta EEG frequencies during entry into natural hypothermia in European ground squirrels. Sleep Wake Res Neth 11:114–119
Su B, Wang X, Drew KL, Perry G, Smith MA, Zhu X (2008) Physiological regulation of tau phosphorylation during hibernation. J Neurochem 105:2098–2108
Swoap SJ, Rathvon M, Gutilla M (2007) AMP does not induce torpor. Am J Physiol Regul Integr Comp Physiol 293:R468–R473
Zhang J, Kaasik K, Blackburn MR, Lee CC (2006) Constant darkness is a circadian metabolic signal in mammals. Nature 439:340–343
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Boerema, A.S., Keijser, J.N., Bouma, H.R., van der Zee, E.A., Strijkstra, A.M. (2012). The Brain at Low Temperature: Tau Hyperphosphorylation Dynamics in Hibernation Torpor. In: Ruf, T., Bieber, C., Arnold, W., Millesi, E. (eds) Living in a Seasonal World. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28678-0_17
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