Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice
Abstract
Background: There is no universally accepted behavioral scoring to define the early development of phenothiazine (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling. [GMJ.2019;8:e1511]References
Rizvi S, Ladino LD, Hernandez-Ronquillo L, Tellez-Zenteno JF. Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure. Seizure. 2017;49:46-53.
https://doi.org/10.1016/j.seizure.2017.02.006
PMid:28242175
Tellez-Zenteno JF, Hernandez-Ronquillo L. A review of the epidemiology of temporal lobe epilepsy. Epilepsy research and treatment. 2012;2012:630853.
https://doi.org/10.1155/2012/630853
PMid:22957234 PMCid:PMC3420432
Zhong Q, Ren BX, Tang FR. Neurogenesis in the Hippocampus of Patients with Temporal Lobe Epilepsy. Current neurology and neuroscience reports. 2016;16(2):20.
https://doi.org/10.1007/s11910-015-0616-3
PMid:26769029
Andres-Mach M, Fike JR, Luszczki JJ. Neurogenesis in the epileptic brain: a brief overview from temporal lobe epilepsy. Pharmacological reports : PR. 2011;63(6):1316-23.
https://doi.org/10.1016/S1734-1140(11)70696-X
Niimi Y, Levison SW. Pediatric brain repair from endogenous neural stem cells of the subventricular zone. Pediatric research. 2018;83(1-2):385-96.
https://doi.org/10.1038/pr.2017.261
PMid:29028220
Kruger GM, Morrison SJ. Brain repair by endogenous progenitors. Cell. 2002;110(4):399-402.
https://doi.org/10.1016/S0092-8674(02)00899-1
Levesque M, Avoli M, Bernard C. Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration. Journal of neuroscience methods. 2016;260:45-52.
https://doi.org/10.1016/j.jneumeth.2015.03.009
PMid:25769270 PMCid:PMC4880459
Loscher W. Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs. Neurochemical research. 2017;42(7):1873-88.
https://doi.org/10.1007/s11064-017-2222-z
PMid:28290134
Buckmaster PS. Laboratory animal models of temporal lobe epilepsy. Comparative medicine. 2004;54(5):473-85.
PMid:15575361
Park JH, Cho H, Kim H, Kim K. Repeated brief epileptic seizures by pentylenetetrazole cause neurodegeneration and promote neurogenesis in discrete brain regions of freely moving adult rats. Neuroscience. 2006;140(2):673-84.
https://doi.org/10.1016/j.neuroscience.2006.02.076
PMid:16616429
Zhu X, Dong J, Shen K, Bai Y, Chao J, Yao H. Neuronal nitric oxide synthase contributes to pentylenetetrazole-kindling-induced hippocampal neurogenesis. Brain research bulletin. 2016;121:138-47.
https://doi.org/10.1016/j.brainresbull.2016.01.010
PMid:26820711
Aniol VA, Stepanichev MY, Lazareva NA, Gulyaeva NV. An early decrease in cell proliferation after pentylenetetrazole-induced seizures. Epilepsy & behavior: E&B. 2011;22(3):433-41.
https://doi.org/10.1016/j.yebeh.2011.08.002
PMid:21907628
Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalography and clinical neurophysiology. 1972;32(3):281-94.
https://doi.org/10.1016/0013-4694(72)90177-0
Dhir A. Pentylenetetrazol (PTZ) kindling model of epilepsy. Current protocols in neuroscience. 2012;Chapter 9:Unit9.37.
Luttjohann A, Fabene PF, van Luijtelaar G. A revised Racine's scale for PTZ-induced seizures in rats. Physiology & behavior. 2009;98(5):579-86.
https://doi.org/10.1016/j.physbeh.2009.09.005
PMid:19772866
Chen Z, Li Z, Sakurai E, Izadi Mobarakeh J, Ohtsu H, Watanabe T et al. Chemical kindling induced by pentylenetetrazol in histamine H(1) receptor gene knockout mice (H(1)KO), histidine decarboxylase-deficient mice (HDC(-/-)) and mast cell-deficient W/W(v) mice. Brain research. 2003;968(1):162-6.
https://doi.org/10.1016/S0006-8993(03)02229-7
Kelly KM. Aging models of acute seizures and epilepsy. Epilepsy currents. 2010;10(1):15-20. 18. Browning RA, Nelson DK. Modification of electroshock and pentylenetetrazol seizure patterns in rats after precollicular transections. Experimental neurology. 1986;93(3):546-56.
https://doi.org/10.1016/0014-4886(86)90174-3
Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harbor perspectives in medicine. 2015;5(6).
https://doi.org/10.1101/cshperspect.a022426
PMid:26033084 PMCid:PMC4448698
Velíšková J, . Behavioral characterization of seizures in rats. In: Pitkanen A,Schwartzkroin P, Moshe S, editors. Models of seizures and epilepsy. San Diego: Elsevier Inc.; 2006.
https://doi.org/10.1016/B978-012088554-1/50050-5
Goddard GV, McIntyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation. Experimental neurology. 1969;25(3):295-330.
https://doi.org/10.1016/0014-4886(69)90128-9
Deisseroth K, Singla S, Toda H, Monje M, Palmer TD, Malenka RC. Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron. 2004;42(4):535-52.
https://doi.org/10.1016/S0896-6273(04)00266-1
Mizoguchi H, Yamada K. Roles of matrix metalloproteinases and their targets in epileptogenesis and seizures. Clinical psychopharmacology and neuroscience: the official scientific journal of the Korean College of Neuropsychopharmacology. 2013;11(2):45-52.
https://doi.org/10.9758/cpn.2013.11.2.45
PMid:24023547 PMCid:PMC3766754
Zhang Q, Liu G, Wu Y, Sha H, Zhang P, Jia J. BDNF promotes EGF-induced proliferation and migration of human fetal neural stem/progenitor cells via the PI3K/Akt pathway. Molecules (Basel, Switzerland). 2011;16(12):10146-56.
https://doi.org/10.3390/molecules161210146
PMid:22146375 PMCid:PMC6264301
Han D, Yamada K, Senzaki K, Xiong H, Nawa H, Nabeshima T. Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats. Journal of neurochemistry. 2000;74(2):792-8.
https://doi.org/10.1046/j.1471-4159.2000.740792.x
PMid:10646532
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