Intra-Hippocampal Injection of Abscisic Acid Attenuates Learning and Memory Deficits, and Changes Oxidative Stress Indices in REM Sleep Deprived Rats

Iranian Journal of Veterinary Science and Technology

دوره 17، شماره 2 - شماره پیاپی 39، شهریور 2025، صفحه 29-37   

نوع مقاله: Research Article

شناسه دیجیتال (DOI): 10.22067/ijvst.2025.86932.1355

نویسندگان

Alireza Fekrat¹؛ Mahzad Abbasnejad²؛ Razieh Kooshki^{* 3}؛ Parastoo Nikkhouy²؛ Mehdi Abbasnejad²

¹Department of Psychiatry, Noureh hospital, Kerman University of Medical Sciences, Kerman, Iran. .

²Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.

³Department of Biology, Faculty of Sciences, Lorestan University, Khorramabad, Iran.

چکیده

This study evaluated whether intra-hippocampal administration of ABA can modulate learning and memory performance and oxidative stress biomarker activities in the cerebral cortex of rats exposed to rapid eye movement (REM) sleep deprivation. Adult male Wistar rats were cannulated in the CA1 area of the hippocampus. After recovery, the rats were subjected to REM sleep deprivation for 4 days. Then, the groups of REM sleep-deprived (SD) rats were treated with ABA (5, 10, and 15 µg) and ABA (10 µg) + bicuculline (Bic), a competitive GABAA receptor antagonist. Memory and learning were evaluated with the Morris water maze (MWM) and shuttle box tests. Moreover, alterations in catalase levels as an antioxidant enzyme, MDA, and H2O2 as oxidant biomarkers were determined in rat brain cortex. REM SD rats indicated noteworthy learning and memory deficits in both the MWM and shuttle box tests when compared to control rats. However, intra-CA1 injection of ABA (10 µg) decreased cognitive impairment in REM SD rats. Bic (1 μg/rat) could not change ABA (10 µg) effects. In addition, an increase in catalase activity and a decrease in MDA and H2O2 were indicated in the brain cortex of ABA (10 µg) and ABA+ Bic treated groups. Overall, the data showed ABA's aptitude to attenuate REM sleep deprivation-induced learning and memory disruption and oxidative damage in rats. Manipulation of the GABAA receptor failed to inhibit ABA effects in REM SD rats.

کلیدواژه‌ها

sleep deprivation؛ abscisic acid؛ bicuculline؛ learning and memory؛ Rat

سایر فایل های مرتبط با مقاله

4-1355-persian abs-F.pdf

مراجع

1.    Gong L, Liu Q. Mobile phone addiction and sleep quality: the mediating role of anxiety and the moderating role of emotion regulation. Behav Sci. 2023;13(3):250. Doi: 0.3390/bs13030250.
2.    Chattu VK, Manzar MD, Kumary S, Burman D, Spence DW, Pandi-Perumal SR. The global problem of insufficient sleep and its serious public health implications. Healthcare; 2018: MDPI.  Doi: 10.3390/healthcare7010001.
3.    Tobaldini E, Costantino G, Solbiati M, Cogliati C, Kara T, Nobili L, et al. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases. Neurosci Biobehav Rev. 2017;74:321-9. Doi: 10.1016/j.neubiorev.2016.07.004.
4.    Shen Y, Lv Q-k, Xie W-y, Gong S-y, Zhuang S, Liu J-y, et al. Circadian disruption and sleep disorders in neurodegeneration. Trans  Neurodegeneration. 2023;12(1):8. Doi: 10.1186/s40035-023-00340-6.
5.    Guan Z, Peng X, Fang J. Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus. Brain Res. 2004;1018(1):38-47. Doi: 10.1016/j.brainres.2004.05.032.
6.    Latchoumane C-F V, Ngo H-V V, Born J, Shin H-S. Thalamic spindles promote memory formation during sleep through triple phase-locking of cortical, thalamic, and hippocampal rhythms. Neuron. http://dx.doi.org/10.1016/j.neuron.2017.06.025 (2017). Doi: 10.1016/j.neuron.2017.06.025.
7.    Abel T, Havekes R, Saletin JM, Walker MP. Sleep, plasticity and memory from molecules to whole-brain networks. Curr Biol. 2013;23(17):R774-R88. Doi: 10.1016/j.cub.2013.07.025.
8.    Havekes R, Canton DA, Park AJ, Huang T, Nie T, Day JP, et al. Gravin orchestrates protein kinase A and β2-adrenergic receptor signaling critical for synaptic plasticity and memory. J  Neurosci. 2012;32(50):18137-49. Doi: 10.1523/JNEUROSCI.3612-12.2012.
9.    Henderson MX, Wirak GS, Zhang Y-q, Dai F, Ginsberg SD, Dolzhanskaya N, et al. Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation. Acta Neuropathologica. 2016;131(4):621-37. Doi: 10.1007/s00401-015-1512-2.
10.    Rolls A, Colas D, Adamantidis A, Carter M, Lanre-Amos T, Heller HC, et al. Optogenetic disruption of sleep continuity impairs memory consolidation. Proc Natl Academy Sci. 2011;108(32):13305-10. Doi: 10.1073/pnas.1015633108.
11.    Matthys D, Gielis J, Debergh P. Ethylene.  Automation and environmental control in plant tissue culture. Springer; 1995. p. 473-91.
12.    Magnone M, Ameri P, Salis A, Andraghetti G, Emionite L, Murialdo G, et al. Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans. FASEB J. 2015;29(12):4783-93. Doi: 10.1096/fj.15-277731. 
13.    Finkelstein RR, Gampala SS, Rock CD. Abscisic acid signaling in seeds and seedlings. Plant Cell. 2002;14(suppl 1):S15-S45.  Doi: 10.1105/tpc.010441.
14.    Qi C-C, Zhang Z, Fang H, Liu J, Zhou N, Ge J-F, et al. Antidepressant effects of abscisic acid mediated by the downregulation of corticotrophin-releasing hormone gene expression in rats. Int  J  Neuropsychopharmacol. 2015;18(4). Doi: 10.1093/ijnp/pyu006.
15.    Qi C-C, Ge J-F, Zhou J-N. Preliminary evidence that abscisic acid improves spatial memory in rats. Phys Behav. 2015;139:231-9. Doi: 10.1016/j.physbeh.2014.11.053. 
16.    Bassaganya-Riera J, Guri AJ, Lu P, Climent M, Carbo A, Sobral BW, et al. Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor γ.  J Biol  Chem. 2011;286(4):2504-16. Doi: 10.1074/jbc.M110.160077.
17.    Sturla L, Fresia C, Guida L, Bruzzone S, Scarfì S, Usai C, et al. LANCL2 is necessary for abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells. J Biol Chem. 2009;284(41):28045-57.  Doi: 10.1074/jbc.M109.035329.
18.    Magnone M, Bruzzone S, Guida L, Damonte G, Millo E, Scarfì S, et al. Abscisic acid released by human monocytes activates monocytes and vascular smooth muscle cell responses involved in atherogenesis. J  Biol Chem. 2009;284(26):17808-18. Doi: 10.1074/jbc.M809546200.
19.    Zocchi E, Basile G, Cerrano C, Bavestrello G, Giovine M, Bruzzone S, et al. ABA-and cADPR-mediated effects on respiration and filtration downstream of the temperature-signaling cascade in sponges. J Cell Sci. 2003;116(4):629-36. Doi: 10.1242/jcs.00277.
20.    Scarfì S, Ferraris C, Fruscione F, Fresia C, Guida L, Bruzzone S, et al. Cyclic ADP-ribose-mediated expansion and stimulation of human mesenchymal stem cells by the plant hormone abscisic acid. Stem Cells. 2008;26(11):2855-64. Doi: 10.1634/stemcells.2008-0488. 
21.    Freitag CM, Miller RJ. Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines? Front  Cell  Neurosci. 2014;8:238. Doi: 10.3389/fncel.2014.00238.
22.    Mollashahi M, Abbasnejad M, Esmaeili-Mahani S. Phytohormone abscisic acid elicits antinociceptive effects in rats through the activation of opioid and peroxisome proliferator-activated receptors β/δ. Eur J Pharmacol. 2018;832:75-80. Doi: 10.1016/j.ejphar.2018.05.013. 
23.    Madadzadeh M, Abbasnejad M, Mollashahi M, Pourrahimi AM, Esmaeili-Mahani S. Phytohormone abscisic acid boosts pentobarbital-induced sleep through activation of GABA-A, PPARβ and PPARγ receptor signaling. Arq de Neuro-Psiquiatria. 2021;79:216-21. Doi: 10.1590/0004-282X-ANP-2019-0393.
24.    Alhola P, Polo-Kantola P. Sleep deprivation: impact on cognitive performance. Neuropsychiatric disease and treatment. 2007;3(5):553-67.
25.    Vaseghi S, Arjmandi-Rad S, Kholghi G, Nasehi M. Inconsistent effects of sleep deprivation on memory function. EXCLI journal. 2021;20:1011. Doi: 10.17179/excli2021-3764.
26.    Jiao Q, Dong X, Guo C, Wu T, Chen F, Zhang K, et al. Effects of sleep deprivation of various durations on novelty-related object recognition memory and object location memory in mice. Behav  Brain Res. 2022;418:113621. Doi: 10.1016/j.bbr.2021.113621.
27.    Ma Y, Liang L, Zheng F, Shi L, Zhong B, Xie W. Association between sleep duration and cognitive decline. JAMA netw open. 2020;3(9):e2013573-e. Doi: 10.1001/jamanetworkopen.2020.13573.
28.    Khorasani A, Abbasnejad M, Esmaeili-Mahani S. Phytohormone abscisic acid ameliorates cognitive impairments in streptozotocin-induced rat model of Alzheimer's disease through PPARβ/δ and PKA signaling. Int J Neurosci. 2019;129(11):1053-65. Doi: 10.1080/00207454.2019.1634067.
29.    Kooshki R, Anaeigoudari A, Abbasnejad M, Askari-Zahabi K, Esmaeili-Mahani S. Abscisic acid interplays with PPARγ receptors and ameliorates diabetes-induced cognitive deficits in rats. Avicenna J Phytomed. 2021;11(3):247.
30.    Swanwick CC, Murthy NR, Mtchedlishvili Z, Sieghart W, Kapur J. Development of γ-aminobutyric acidergic synapses in cultured hippocampal neurons. J Comp Neurol. 2006;495(5):497-510. Doi: 10.1002/cne.20897.
31.    Tyzio R, Represa A, Jorquera I, Ben-Ari Y, Gozlan H, Aniksztejn L. The establishment of GABAergic and glutamatergic synapses on CA1 pyramidal neurons is sequential and correlates with the development of the apical dendrite. J Neurosci. 1999;19(23):10372-82.  Doi: 10.1523/JNEUROSCI.19-23-10372.1999.

32.    Makkar SR, Zhang SQ, Cranney J. Behavioral and neural analysis of GABA in the acquisition, consolidation, reconsolidation, and extinction of fear memory. Neuropsychopharmacology. 2012;37(7):1793. Doi: 10.1038/npp.2010.53.
33.    Whissell PD, Eng D, Lecker I, Martin LJ, Wang D-S, Orser BA. Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus. Front  Neural Circuits. 2013;7:146. Doi: 10.3389/fncir.2013.00146. 
34.    Wimmer GE, Poldrack RA. Reward learning and working memory: Effects of massed versus spaced training and post-learning delay period. Mem  Cogn. 2022;50(2):312-24. Doi: 10.3758/s13421-021-01233-7. 
35.    Chen P, Ban W, Wang W, You Y, Yang Z. The Devastating Effects of Sleep Deprivation on Memory: Lessons from Rodent Models. Clock Sleep. 2023;5(2):276-94. Doi: 10.3390/clockssleep5020022.
36.    Celik I, Turker M, Tuluce Y. Abcisic acid and gibberellic acid cause increased lipid peroxidation and fluctuated antioxidant defense systems of various tissues in rats. J Hazardous Mat. 2007;148(3):623-9. Doi: 10.1016/j.jhazmat.2007.03.018. 
37.    Soti M, Abbasnejad M, Kooshki R, Esmaeili-Mahani S. Central microinjection of phytohormone abscisic acid changes feeding behavior, decreases body weight, and reduces brain oxidative stress in rats. Nutr  Neurosci. 2019;22(10):678-87. Doi: 10.1080/1028415X.2018.1431093.
38.    Chen X, Ding C, Liu W, Liu X, Zhao Y, Zheng Y, et al. Abscisic acid ameliorates oxidative stress, inflammation, and apoptosis in thioacetamide-induced hepatic fibrosis by regulating the NF-кB signaling pathway in mice. Eur  J Pharmacol. 2021;891:173652. Doi: 10.1016/j.ejphar.2020.173652.
39.    Naderi R, Esmaeili-Mahani S, Abbasnejad M. Phosphatidylinositol-3-kinase and protein kinase C are involved in the pro-cognitive and anti-anxiety effects of phytohormone abscisic acid in rats. Biomed Pharmacother. 2017;96:112-9. Doi: 10.1016/j.biopha.2017.09.089.
40.    Kooshki R, Abbasnejad M, Esmaeili-Mahani S, Raoof M. The Modulatory Role of Orexin 1 Receptor in CA1 on Orofacial Pain-induced Learning and Memory Deficits in Rats. Basic Clin  Neurosci. 2017;8(3):213. Doi: 10.18869/nirp.bcn.8.3.213.
41.    McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG, Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci. 2003;23(29):9687-95. Doi: 10.1523/JNEUROSCI.23-29-09687.2003.
42.    Morris RG, Garrud P, Rawlins Ja, O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature. 1982;297(5868):681-3.
43.    Kameyama T, Nabeshima T, Kozawa T. Step-down-type passive avoidance-and escape-learning method: Suitability for experimental amnesia models. J Pharmacological Met. 1986;16(1):39-52. Doi: 10.1016/0160-5402(86)90027-6.
44.    Hodges DM, DeLong JM, Forney CF, Prange RK. Improving the thiobarbituric acid-reactive-substances assay for estimating lipid peroxidation in plant tissues containing anthocyanin and other interfering compounds. Planta. 1999;207(4):604-11. Doi: 10.1007/s004250050524
45.    Velikova V, Yordanov I, Edreva A. Oxidative stress and some antioxidant systems in acid rain-treated bean plants. Plants Sci. 2000; 59-66. Doi: 10.1016/S0168-9452(99)00197-1.