Abstract
Status epilepticus (SE) is a common neurological condition associated with high rates of mortality and permanent brain injury. SE usually leads to neuronal death which may be accompanied by edema, epileptogenesis and learning impairment. Aquaporin-4 (AQP4), is a transmembrane water channel protein in the neuropil of the central nervous system that has an important role in water transport in the brain; AQP4 expression is altered in many pathological conditions such as changes in the blood- brain barrier and/or astrocytic activation, including seizures. AQP4 was shown to be downregulated in the piriform cortex and the hippocampus after SE. Although it is normally expressed at a high level in the cerebellum, little is known about AQP4 levels in the cerebellum following SE. We addressed this in the present study in a mouse model of pilocarpine-induced SE. We found that AQP4 expression was reduced from 3 h to 3 days after SE, with the levels recovering on day 7. Moreover, mice in the acute post-SE stages exhibited impaired motor coordination and learning. These results indicate that cerebellar damage following SE involves changes in AQP4 expression.
Similar content being viewed by others
References
Badaut J, Lasbennes F, Magistretti PJ, Regli L (2002) Aquaporins in brain: distribution, physiology, and pathophysiology. J Cereb Blood Flow Metab 22:367–378. doi:10.1097/00004647-200204000-00001
Buckmaster PS, Haney MM (2012) Factors affecting outcomes of pilocarpine treatment in a mouse model of temporal lobe epilepsy. Epilepsy Res 102:153–159. doi:10.1016/j.eplepsyres.2012.05.012
Cavalheiro EA, Santos NF, Priel MR (1996) The pilocarpine model of epilepsy in mice. Epilepsia 37:1015–1019
Clopath C (2012) Synaptic consolidation: an approach to long-term learning. Cogn Neurodyn 6:251–257. doi:10.1007/s11571-011-9177-6
Costa C, Tortosa R, Domenech A, Vidal E, Pumarola M, Bassols A (2007) Mapping of aggrecan, hyaluronic acid, heparan sulphate proteoglycans and aquaporin 4 in the central nervous system of the mouse. J Chem Neuroanat 33:111–123. doi:10.1016/j.jchemneu.2007.01.006
Covolan L, Mello LE (2000) Temporal profile of neuronal injury following pilocarpine or kainic acid-induced status epilepticus. Epilepsy Res 39:133–152
Curia G, Longo D, Biagini G, Jones RS, Avoli M (2008) The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods 172:143–157. doi:10.1016/j.jneumeth.2008.04.019
DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG (1995) Epidemiology of status epilepticus. J Clin Neurophysiol 12:316–325
Du M, Li J, Wang R, Wu Y (2016) The influence of potassium concentration on epileptic seizures in a coupled neuronal model in the hippocampus. Cogn Neurodyn 10:405–414. doi:10.1007/s11571-016-9390-4
Elger CE, Helmstaedter C, Kurthen M (2004) Chronic epilepsy and cognition. Lancet Neurol 3:663–672. doi:10.1016/s1474-4422(04)00906-8
Emerson MR, Nelson SR, Samson FE, Pazdernik TL (1999) Hypoxia preconditioning attenuates brain edema associated with kainic acid-induced status epilepticus in rats. Brain Res 825:189–193
Freichel C, Potschka H, Ebert U, Brandt C, Loscher W (2006) Acute changes in the neuronal expression of GABA and glutamate decarboxylase isoforms in the rat piriform cortex following status epilepticus. Neuroscience 141:2177–2194. doi:10.1016/j.neuroscience.2006.05.040
Fujikawa DG (1995) Neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia 36:186–195
Fukuda AM, Adami A, Pop V, Bellone JA, Coats JS, Hartman RE, Ashwal S, Obenaus A, Badaut J (2013) Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery. J Cereb Blood Flow Metab 33:1621–1632. doi:10.1038/jcbfm.2013.118
Glickstein M, Strata P, Voogd J (2009) Cerebellum: history. Neuroscience 162:549–559. doi:10.1016/j.neuroscience.2009.02.054
Groticke I, Hoffmann K, Loscher W (2007) Behavioral alterations in the pilocarpine model of temporal lobe epilepsy in mice. Exp Neurol 207:329–349. doi:10.1016/j.expneurol.2007.06.021
Haj-Yasein NN, Vindedal GF, Eilert-Olsen M, Gundersen GA, Skare O, Laake P, Klungland A, Thoren AE, Burkhardt JM, Ottersen OP, Nagelhus EA (2011) Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet. Proc Natl Acad Sci U S A 108:17815–17820. doi:10.1073/pnas.1110655108
Hubbard JA, Hsu MS, Seldin MM, Binder DK (2015) Expression of the astrocyte water channel aquaporin-4 in the mouse brain. ASN Neuro. doi:10.1177/1759091415605486
Itoh K, Inamine M, Oshima W, Kotani M, Chiba Y, Ueno M, Ishihara Y (2015) Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam. Brain Res 1608:225–234. doi:10.1016/j.brainres.2015.03.005
Kim JE, Ryu HJ, Yeo SI, Seo CH, Lee BC, Choi IG, Kim DS, Kang TC (2009) Differential expressions of aquaporin subtypes in astroglia in the hippocampus of chronic epileptic rats. Neuroscience 163:781–789. doi:10.1016/j.neuroscience.2009.07.028
Kim JE, Yeo SI, Ryu HJ, Kim MJ, Kim DS, Jo SM, Kang TC (2010) Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus. J Comp Neurol 518:4612–4628. doi:10.1002/cne.22482
Lee DJ, Hsu MS, Seldin MM, Arellano JL, Binder DK (2012) Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis. Exp Neurol 235:246–255. doi:10.1016/j.expneurol.2012.02.002
Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6:159–163. doi:10.1038/72256
Manley GT, Binder DK, Papadopoulos MC, Verkman AS (2004) New insights into water transport and edema in the central nervous system from phenotype analysis of aquaporin-4 null mice. Neuroscience 129:983–991. doi:10.1016/j.neuroscience.2004.06.088
Mauk MD, Medina JF, Nores WL, Ohyama T (2000) Cerebellar function: coordination, learning or timing? Curr Biol 10:R522–R525
Medina JF, Mauk MD (2000) Computer simulation of cerebellar information processing. Nat Neurosci 3(Suppl):1205–1211. doi:10.1038/81486
Muller CJ, Groticke I, Hoffmann K, Schughart K, Loscher W (2009) Differences in sensitivity to the convulsant pilocarpine in substrains and sublines of C57BL/6 mice. Genes Brain Behav 8:481–492. doi:10.1111/j.1601-183X.2009.00490.x
Murphy GG (2013) Spatial learning and memory-what’s TLE got to do with it? Epilepsy Curr 13:26–29. doi:10.5698/1535-7511-13.1.26
Nagelhus EA, Mathiisen TM, Ottersen OP (2004) Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 129:905–913. doi:10.1016/j.neuroscience.2004.08.053
Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR (2010) Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 51:883–890. doi:10.1111/j.1528-1167.2009.02481.x
Nico B, Ribatti D, Frigeri A, Nicchia GP, Corsi P, Svelto M, Roncali L (2002) Aquaporin-4 expression during development of the cerebellum. Cerebellum 1:207–212. doi:10.1080/14734220260418439
Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP (1997) Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 17:171–180
Oliveira CV, Grigoletto J, Funck VR, Ribeiro LR, Royes LF, Fighera MR, Furian AF, Oliveira MS (2015) Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice. Physiol Behav 143:142–150. doi:10.1016/j.physbeh.2015.03.004
Oshio K, Binder DK, Yang B, Schecter S, Verkman AS, Manley GT (2004) Expression of aquaporin water channels in mouse spinal cord. Neuroscience 127:685–693. doi:10.1016/j.neuroscience.2004.03.016
Papadopoulos MC, Verkman AS (2013) Aquaporin water channels in the nervous system. Nat Rev Neurosci 14:265–277. doi:10.1038/nrn3468
Racine RJ (1972) Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294
Rice AC, DeLorenzo RJ (1998) NMDA receptor activation during status epilepticus is required for the development of epilepsy. Brain Res 782:240–247
Rowley S, Patel M (2013) Mitochondrial involvement and oxidative stress in temporal lobe epilepsy. Free Radic Biol Med 62:121–131. doi:10.1016/j.freeradbiomed.2013.02.002
Shadmehr R, Brashers-Krug T (1997) Functional stages in the formation of human long-term motor memory. J Neurosci 17:409–419
Shadmehr R, Holcomb HH (1997) Neural correlates of motor memory consolidation. Science 277:821–825
Sharma N, Baxter MG, Petravicz J, Bragg DC, Schienda A, Standaert DG, Breakefield XO (2005) Impaired motor learning in mice expressing torsinA with the DYT1 dystonia mutation. J Neurosci 25:5351–5355. doi:10.1523/jneurosci.0855-05.2005
Sperk G (1994) Kainic acid seizures in the rat. Prog Neurobiol 42:1–32
Stewart LS, Persinger MA (2001) Ketamine prevents learning impairment when administered immediately after status epilepticus onset. Epilepsy Behav 2:585–591. doi:10.1006/ebeh.2001.0272
Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinrok Z, Turski L (1983) Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav Brain Res 9:315–335
Vella J, Zammit C, Di Giovanni G, Muscat R, Valentino M (2015) The central role of aquaporins in the pathophysiology of ischemic stroke. Front Cell Neurosci 9:108. doi:10.3389/fncel.2015.00108
Wei P, Blundon JA, Rong Y, Zakharenko SS, Morgan JI (2011) Impaired locomotor learning and altered cerebellar synaptic plasticity in pep-19/PCP4-null mice. Mol Cell Biol 31:2838–2844. doi:10.1128/mcb.05208-11
Xing Y, Qin Y, Jing W, Zhang Y, Wang Y, Guo D, Xia Y, Yao D (2016) Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats. Cogn Neurodyn 10:23–30. doi:10.1007/s11571-015-9361-1
Zhang C, Chen J, Lu H (2015) Expression of aquaporin-4 and pathological characteristics of brain injury in a rat model of traumatic brain injury. Mol Med Rep 12:7351–7357. doi:10.3892/mmr.2015.4372
Acknowledgements
The works were supported by Grants from the Department of Neurosurgery, Nanchong Central Hospital, Second Affiliated Hospital of North Sichuan Medical College.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that have no conflict of interest.
Rights and permissions
About this article
Cite this article
Tang, H., Shao, C. & He, J. Down-regulated expression of aquaporin-4 in the cerebellum after status epilepticus. Cogn Neurodyn 11, 183–188 (2017). https://doi.org/10.1007/s11571-016-9420-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11571-016-9420-2