|
|
|
|
|
| Protective effect of leptin on seizure brain injury in neonatal rats and its effect on expression of CB-D28k in hippocampus |
| Li Ya-chao, Li Li-li, Jin Mei-fang, Gao Yuan-yuan, Chen ni-na, Wang Dan-dan, Ni Hong |
| Department of Neurology Laboratory, Institute of Pediatric Medicine, Children′s Hospital Affiliated to Soochow University, Suzhou 215000, China |
|
|
|
|
Abstract Objective To investigate the neuroprotective effect of leptin intervention in the acute phase on brain injury and on the expression of CB-D28k in hippocampus in seizure neonatal rats. Methods Seven-day-old Sprague-Dawley rats were randomly divided into 4 groups: blank control group (Control group), Leptin control group (Leptin group), simple seizure group (RS) and Leptin intervention group (RS+Leptin group). The rats in the seizure group and the Leptin intervention group were treated with trifluoroether to induce seizure for 30 minutes for 7 days. The Leptin control group and the Leptin intervention group were received Leptin 4 mg/kg intraperitoneally after 1 hour of daily seizure. On the 14 day (24 hours after the last seizure), 5 rats in each group were randomly sacrificed and hippocampus were taken. Western blot was used to evaluate the expression of CB-D28k in hippocampus. Real-time reverse-transcription polymerase chain reactions (RT-PCRs) were used to detect the expression of CB-D28k mRNA in hippocampus. The neurobehavioral test was performed on P33 in each group. Results There were significant differences in the number of error among the four groups, with it in the RS group significantly more increaser than in the control group (F=5.471，F=13.775，P<0.05). Compared with the control group, the latency of the RS group was significantly shorter (times：1.40±0.52 vs. 0.80±0.42，P<0.05); compared with the RS group, the latency of RS+Leptin group was significantly longer (times：0.60±0.52 vs.1.40±0.52，P<0.05). The expression of CB-D28k and mRNA in the seizure group was significantly decreased compared with the control group (0.44±0.09 vs.1.29±0.20，0.49±0.10 vs.1.08±0.16，P<0.05), and the expression of CB-D28k and mRNA in the RS+Leptin group was significantly increased compared with RS group (0.44±0.09 vs.1.22±0.21，0.49±0.10 vs.0.93±0.09，P<0.05). Conclusion The acute phase intervention of Leptin has neuroprotective effects on neurobehavioral injury induced by seizure in neonatal rats, and its mechanism may be related to the regulation of CB-D28k expression in hippocampus.
|
|
|
|
Corresponding Authors:
Ni Hong, E-mail: nhdortor@163.com
|
|
|
|
| ［1］姜明, 胡洪涛, 闫欣,等. 血清尿酸水平对癫痫与晕厥的鉴别诊断价值［J］. 中国急救医学, 2018， 38(5):403-405.
［2］秦炯. 重视对儿童癫（癎）共患病的认识与研究［J］. 中华儿科杂志, 2007, 45(8):561-563.
［3］Holden KF, Lindquist K, Tylavsky FA, et al. Serum leptin level and cognition in the elderly: Findings from the Health ABC Study［J］. Neurobiology of Aging, 2009, 30(9):1483-1489.
［4］Lieb W, Beiser AS, Vasan RS, et al. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging［J］. JAMA, 2009, 302(23):2565-2572.
［5］Zeki Al Hazzouri A, Haan MN, Whitmer RA, et al. Central Obesity, leptin and cognitive decline: the sacramento area latino study on aging［J］. Dement Geriatr Cogn Disord, 2012, 33(6):400-409.
［6］Witte AV, Kbe T, Graunke A, et al. Impact of leptin on memory function and hippocampal structure in mild cognitive impairment［J］. Human Brain Mapp, 2016, 37(12):4539-4549.
［7］Farr SA, Banks WA, Morley JE. Effects of leptin on memory processing［J］. Peptides, 2006, 27(6):1420-1425.
［8］Sato T, Hanyu H, Hirao K, et al. Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease［J］. Neurobiol Aging, 2011, 32(9):1626-1633.
［9］Searcy JL, Phelps JT, Pancani T, et al. Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer′s disease［J］. J Alzheimers Dis, 2012, 30(4):943-961.
［10］Mello LE, Cavalheiro EA, Tan AM, et al. Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting［J］. Epilepsia, 2010, 34(6):985-995.
［11］Holmes GL, Tian C, Hernan AE, et al. Alterations in sociability and functional brain connectivity caused by early-life seizures is reversed by bumetanide［J］. Neurobiol Dis, 2015, 77:204-219.
［12］Hernan AE, Holmes GL, Isaev D, et al. Altered short-term plasticity in the prefrontal cortex after early life seizures［J］. Neurobiol Dis, 2013, 50:120-126.
［13］Tian T, Ni H, Sun BL. Neurobehavioral deficits in a rat model of recurrent neonatal seizures are prevented by a ketogenic diet and correlate with hippocampal zinc/lipid transporter signals［J］. Biol Trace Elem Res, 2015, 167(2):251-258.
［14］Ni H, Sun Q, Tian T, et al. Long-term expression of metabolism-associated genes in the rat hippocampus following recurrent neonatal seizures and its regulation by melatonin［J］. Mol Med Rep, 2015, 12(2):2727-2734.
［15］Liberini CG, Boyle CN, Cifani C, et al. Amylin receptor components and the leptin receptor are co‐expressed in single rat area postrema neurons［J］. Eur J Neurosci, 2016, 43(5):653-661.
［16］Smith PM, Brzezinska P, Hubert F, et al. Leptin influences the excitability of area postrema neurons［J］. Am J Physiol Regul Integr Comp Physiol, 2016, 310(5):R440-448.
［17］O′Malley D, Macdonald N, Mizielinska S, et al. Leptin promotes rapid dynamic changes in hippocampal dendritic morphology［J］.Mol Cell Neurosci, 2007, 35(4):559-572.
［18］Garza JC, Guo M, Zhang W, et al. Leptin increases adult hippocampal neurogenesis in vivo and in vitro［J］. J Biol Chem, 2008, 283(26):18 238-18 247.
［19］Miao T, Wu D, Zhang Y, et al. Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons［J］. J Neurosci, 2006, 26(37):9512-9519.
［20］Ni H, Sun Q, Tian T, et al. Prophylactic treatment with melatonin before recurrent neonatal seizures: effects on long-term neurobehavioral changes and the underlying expression of metabolismrelated genes in rat hippocampus and cerebral cortex［J］. Pharmacol Biochem Behav, 2015, 133:25-30.
［21］Deng ZH, Liao J, Zhang JY, et al. Inhibition of the connexin 43 elevation may be involved in the neuroprotective activity of leptin against brain ischemic injury［J］. Cell Mol Neurobiol, 2014, 34(6):871-879.
［22］Jin MF, Ni H, Li LL. Leptin maintained zinc homeostasis against glutamate-induced excitotoxicity by preventing mitophagymediated mitochondrial activation in HT22 hippocampal neuronal cells［J］. Front Neurol, 2018, 9:322.
［23］Doherty GH, Beccanokelly D, Yan SD, et al. Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β［J］. Neurobiology of Aging, 2013, 34(1):226-237.
［24］Pérez-González R, Alvira-Botero MX, Robayo O, et al. Leptin gene therapy attenuates neuronal damages evoked by amyloid-β and rescues memory deficits in APP/PS1 mice［J］. Gene Ther, 2014, 21(3):298-308.
［25］Molinari S, Battini R, Ferrari S, et al. Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression［J］. Proc Natl Acad Sci USA, 1996, 93(15):8028-8033.
［26］Berggrd T, Miron S, Onnerfjord P, et al. Calbindin D28k exhibits properties characteristic of a Ca2+ sensor［J］. J Biol Chem, 2002, 277(19):16 662-16 672.
［27］Lee YJ, Yan BC, Park JH, et al. Differences of calcium binding proteins immunoreactivities in the young hippocampal CA1 region from the adult following transient ischemic damage［J］. J Neurol Sci, 2013, 326(1-2):40-47.
［28］Verdaguer E, Brox S, Petrov D, et al. Vulnerability of Calbindin, Calretinin and Parvalbumin in a transgenic/knock-in APPswe/PS1dE9 mouse model of Alzheimer disease together with disruption of hippocampal neurogenesis［J］. Exp Gerontol, 2015, 69:176-188.
［29］Murayama N, Noshita T, Ogino R, et al. SUN11602-induced hyperexpression of calbindin D-28k is pivotal for the survival of hippocampal neurons under neurotoxic conditions［J］. Brain Res, 2015, 1594:71-81. |
|
|
|
Address: 1 North 2nd Street,
Zhongguancun, 
