Effect of Recombinant Insulin-like Growth Factor-2 Injected into the Hippocampus on Memory Impairment Following Hippocampal Intracerebral Hemorrhage in Rats
DOI:
https://doi.org/10.31661/gmj.v7i.1353Keywords:
Intracerebral Hemorrhage, IGF-2, Learning, Memory, HippocampusAbstract
Background: Insulin-like growth factor 2 (IGF-2) is a growth factor and an anti-inflammatory cytokine that plays a pivotal role in memory. In this study, we examined the effect of recombinant IGF-2 on memory impairment due to intracerebral hemorrhage (ICH). Avoidance and recognition memory, locomotor activity, neurological deficit score (NDS), and the level of the IGF-2 gene expression were evaluated. Materials and Methods: To induce ICH, 100 μL of autologous blood was injected into the left hippocampus of male Sprague Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 minutes after the induction of ICH. Then, over two weeks, NDS, locomotor activity, passive avoidance, and novel object recognition (NOR) test were evaluated. Finally, the level of IGF-2 gene expression was evaluated by using the real-time polymerase chain reaction technique. Result: Our results indicated that recombinant IGF-2 injection significantly increased step-through latency (P<0.001) and total time spent in the dark box (P<0.01). However, no significant difference was seen in recognition memory and NDS. Locomotor activity did not significantly change in any group. A significantly reduced level of IGF-2 was observed after two weeks (P<0.05). Conclusion:The results of this study show that a single dose of recombinant IGF-2 injection can influence hippocampus-dependent memories. Importantly, IGF-2 did not change locomotor activity and NDS after two weeks, which probably represents its specific function in memory.[GMJ.2018;7:e1353]
References
Stern SA, Kohtz AS, Pollonini G, Alberini CM. Enhancement of memories by systemic administration of insulin-like growth factor II. Neuropsychopharmacology.2014; 39(9): 2179–90. https://doi.org/10.1038/npp.2014.69PMid:24642597 PMCid:PMC4104337 Manno EM. Update on Intracerebral Hemorrhage. Contin Lifelong Learn Neurol. 2012; 18(3): 598–610. https://doi.org/10.1212/01.CON.0000415430.99394.3ePMid:22810251 Rynkowski MA, Kim GH, Komotar RJ, Otten ML, Ducruet AF, Zacharia BE, et al. A mouse model of intracerebral hemorrhage using autologous blood infusion. Nat Protoc. 2008; 3(1): 122–8. https://doi.org/10.1038/nprot.2007.513PMid:18193028 Zhou L, Liu C, Wang Z, Shen H, Wen Z, Chen D, et al. Pannexin-1 is involved in neuronal apoptosis and degeneration in experimental intracerebral hemorrhage in rats. Mol Med Rep. 2018; 17(4): 5684–91. https://doi.org/10.3892/mmr.2018.8624Evans MA, Kim HA, Ling YH, Uong S, Vinh A, De Silva TM, et al. Vitamin D3 Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke. NeuroMolecular Med. 2018; 20(1): 147–59. https://doi.org/10.1007/s12017-018-8484-zPMid:29476479 PMCid:PMC5834596 Guerra GP, Mello CF, Bochi GV, Pazini AM, Fachinetto R, Dutra RC, et al. Hippocampal PKA/CREB pathway is involved in the improvement of memory induced by spermidine in rats. Neurobiol Learn Mem. 2011; 96(2): 324–32. https://doi.org/10.1016/j.nlm.2011.06.007PMid:21708277 Alberini CM. Transcription Factors in Long-Term Memory and Synaptic Plasticity. Physiol Rev. 2009; 89(1): 121–45. https://doi.org/10.1152/physrev.00017.2008PMid:19126756 PMCid:PMC3883056 Bartsch D, Casadio A, Karl KA, Serodio P, Kandel ER. CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation. Cell. 1998; 95(2): 211–23. https://doi.org/10.1016/S0092-8674(00)81752-3Alberini CM, Ghirardi M, Metz R, Kandel ER. C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia. Cell. 1994; 76(6): 1099–114. https://doi.org/10.1016/0092-8674(94)90386-7Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, et al. A critical role for IGF-II in memory consolidation and enhancement. Nature. 2011; 469(7331): 491–9. https://doi.org/10.1038/nature09667PMid:21270887 PMCid:PMC3908455 Nielsen FC. The molecular and cellular biology of insulin-like growth factor II. Prog Growth Factor Res. 1992; 4(3): 257–90. https://doi.org/10.1016/0955-2235(92)90023-BFernandez AM, Torres-Alemán I. The many faces of insulin-like peptide signalling in the brain. Nat Rev Neurosci. 2012; 13(4): 225–39. https://doi.org/10.1038/nrn3209PMid:22430016 Kihara T, Shimohama S. Alzheimer's disease and acetylcholine receptors. Acta Neurobiol Exp (Wars). 2004; 64(1): 99–105. Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, et al. Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial. Stroke. 1995; 26(4): 602–5. https://doi.org/10.1161/01.STR.26.4.602PMid:7709405 Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, et al. Selfotel in acute ischemic stroke : possible neurotoxic effects of an NMDA antagonist. Stroke. 2000; 31(2): 347–54. https://doi.org/10.1161/01.STR.31.2.347PMid:10657404 Schmeisser MJ, Baumann B, Johannsen S, Vindedal GF, Jensen V, Hvalby OC, et al. I B Kinase/Nuclear Factor B-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling. J Neurosci. 2012; 32(16): 5688–703. https://doi.org/10.1523/JNEUROSCI.0111-12.2012PMid:22514330 Suh H-S, Zhao M-L, Derico L, Choi N, Lee SC. Insulin-like growth factor 1 and 2 (IGF1, IGF2) expression in human microglia: differential regulation by inflammatory mediators. J Neuroinflammation. 2013; 10(1): 805. https://doi.org/10.1186/1742-2094-10-37PMid:23497056 PMCid:PMC3607995 Sierra A, Beccari S, Diaz-Aparicio I, Encinas JM, Comeau S, Tremblay M-È. Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis. Neural Plast. 2014; 2014: 1–15. https://doi.org/10.1155/2014/610343PMid:24772353 PMCid:PMC3977558 Council NR. Guide for the Care and Use of Laboratory Animals [Internet]. Washington, D.C.: National Academies Press. 2011. Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother. 2010; 1(2): 87–93. https://doi.org/10.4103/0976-500X.72350PMid:21350616 PMCid:PMC3043327 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. Elsevier. 2007. Geiger BM, Frank LE, Caldera-Siu AD, Pothos EN. Survivable stereotaxic surgery in rodents. J Vis Exp. 2008;(20). Krafft PR, Rolland WB, Duris K, Lekic T, Campbell A, Tang J, et al. Modeling Intracerebral Hemorrhage in Mice: Injection of Autologous Blood or Bacterial Collagenase. J Vis Exp. 2012;(67): e4289. Geiger BM, Frank LE, Caldera-Siu AD, Pothos EN. Survivable stereotaxic surgery in rodents. J Vis Exp. 2008;(20). Krafft PR, Rolland WB, Duris K, Lekic T, Campbell A, Tang J, et al. Modeling Intracerebral Hemorrhage in Mice: Injection of Autologous Blood or Bacterial Collagenase. J Vis Exp. 2012;(67): e4289. https://doi.org/10.3791/4289Wen Z, Mei B, Li H, Dou Y, Tian X, Shen M, et al. P2X7 Participates in Intracerebral Hemorrhage-Induced Secondary Brain Injury in Rats via MAPKs Signaling Pathways. Neurochem Res. 2017; 42(8): 2372–83. https://doi.org/10.1007/s11064-017-2257-1PMid:28488233 Sansing LH, Kasner SE, McCullough L, Agarwal P, Welsh FA, Kariko K. Autologous Blood Injection to Model Spontaneous Intracerebral Hemorrhage in Mice. J Vis Exp. 2011;(54). Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke. 1995; 26(4): 627–34; discussion 635. Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke. 1995; 26(4): 627–34; discussion 635. https://doi.org/10.1161/01.STR.26.4.627PMid:7709410 Liu H, Sun X, Zou W, Leng M, Zhang B, Kang X, et al. Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke. Complement Ther Med. 2017; 32: 85–90. https://doi.org/10.1016/j.ctim.2017.03.014PMid:28619309 Zhu W, Gao Y, Chang C-F, Wan J, Zhu S, Wang J. Mouse Models of Intracerebral Hemorrhage in Ventricle, Cortex, and Hippocampus by Injections of Autologous Blood or Collagenase. Ahmad M, editor. PLoS One. 2014; 9(5): e97423. Pan X, Jiang T, Zhang L, Zheng H, Luo J, Hu X. Physical Exercise Promotes Novel Object Recognition Memory in Spontaneously Hypertensive Rats after Ischemic Stroke by Promoting Neural Plasticity in the Entorhinal Cortex. Front Behav Neurosci. 2017; 11: 185. https://doi.org/10.3389/fnbeh.2017.00185PMid:29167635 PMCid:PMC5682296 Hansen KF, Sakamoto K, Wayman GA, Impey S, Obrietan K. Transgenic miR132 Alters Neuronal Spine Density and Impairs Novel Object Recognition Memory. Dawson TM, editor. PLoS One. 2010; 5(11): e15497. Esmaeili Tazangi P, Moosavi SMS, Shabani M, Haghani M. Erythropoietin improves synaptic plasticity and memory deficits by decrease of the neurotransmitter release probability in the rat model of Alzheimer's disease. Pharmacol Biochem Behav. 2015; 130: 15–21. https://doi.org/10.1016/j.pbb.2014.12.011PMid:25553822 Haghani M, Shabani M, Javan M, Motamedi F, Janahmadi M. CB1 Cannabinoid Receptor Activation Rescues Amyloid ß-Induced Alterations in Behaviour and Intrinsic Electrophysiological Properties of Rat Hippocampal CA1 Pyramidal Neurones. Cell Physiol Biochem. 2012; 29(3–4): 391–406. https://doi.org/10.1159/000338494PMid:22508047 Pascual-Lucas M, Viana da Silva S, Di Scala M, Garcia-Barroso C, Gonzalez-Aseguinolaza G, Mulle C, et al. Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice. EMBO Mol Med. 2014; 6(10): 1246–62. https://doi.org/10.15252/emmm.201404228PMid:25100745 PMCid:PMC4287930 Nader K, Schafe GE, LeDoux JE. The labile nature of consolidation theory. Nat Rev Neurosci. 2000; 1(3): 216–9. https://doi.org/10.1038/35044580PMid:11257912 Bramham CR, Alme MN, Bittins M, Kuipers SD, Nair RR, Pai B, et al. The Arc of synaptic memory. Exp brain Res. 2010; 200(2): 125–40. https://doi.org/10.1007/s00221-009-1959-2PMid:19690847 PMCid:PMC2803749 Steinmetz AB, Johnson SA, Iannitelli DE, Pollonini G, Alberini CM. Insulin-like growth factor 2 rescues aging-related memory loss in rats. Neurobiol Aging. 2016; 44: 9–21. https://doi.org/10.1016/j.neurobiolaging.2016.04.006PMid:27318130 PMCid:PMC4913033 Lee Y, Lee YW, Gao Q, Lee Y, Lee HE, Ryu JH. Exogenous insulin-like growth factor 2 administration enhances memory consolidation and persistence in a time-dependent manner. Brain Res. 2015; 1622: 466–73. https://doi.org/10.1016/j.brainres.2015.07.002PMid:26168901 Labandeira-Garcia JL, Costa-Besada MA, Labandeira CM, Villar-Cheda B, RodrÃguez-Perez AI. Insulin-Like Growth Factor-1 and Neuroinflammation. Front Aging Neurosci. 2017; 9: 365. https://doi.org/10.3389/fnagi.2017.00365PMid:29163145 PMCid:PMC5675852 Wynes MW, Riches DWH. Induction of macrophage insulin-like growth factor-I expression by the Th2 cytokines IL-4 and IL-13. J Immunol. 2003; 171(7): 3550–9. https://doi.org/10.4049/jimmunol.171.7.3550Kaur C, Sivakumar V, Dheen ST, Ling EA. Insulin-like growth factor I and II expression and modulation in amoeboid microglial cells by lipopolysaccharide and retinoic acid. Neuroscience. 2006; 138(4): 1233–44. https://doi.org/10.1016/j.neuroscience.2005.12.025PMid:16448778 Alberini CM, Chen DY. Memory enhancement: consolidation, reconsolidation and insulin-like growth factor 2. Trends Neurosci. 2012; 35(5): 274–83. https://doi.org/10.1016/j.tins.2011.12.007PMid:22341662 PMCid:PMC3348400 Livingstone C. IGF2 and cancer. Endocr Relat Cancer. 2013; 20(6): R321–39. https://doi.org/10.1530/ERC-13-0231PMid:24080445 Brouwer-Visser J, Huang GS. IGF2 signaling and regulation in cancer. Cytokine Growth Factor Rev. 2015. 26(3): 371–7. https://doi.org/10.1016/j.cytogfr.2015.01.002PMid:25704323
