Effect of oleuropein on cognitive deficits and changes in hippocampal brain-derived neurotrophic factor and cytokine expression in a rat model of post-traumatic stress disorder
Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. This psychopathological response to traumatic stressors induces learning and memory deficits in rats. Oleuropein (OLE), a major compound in olive leaves, has been reported to possess several pharmacological properties, including anti-cancer, anti-diabetic, anti-atherosclerotic and neuroprotective activities. However, the cognitive effects of OLE and its mechanism of action have remained unclear in PTSD. In this study, we examined whether OLE improved spatial cognitive impairment induced in rats following single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or various doses of OLE for 14 consecutive days after the SPS procedure. The SPS procedure resulted in cognitive impairment in the object recognition task and the Morris water maze test, which was reversed by OLE (100 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction analysis, the administration of OLE significantly alleviated memory-associated decreases in the levels of brain-derived neurotrophic factor and cAMP response element-binding protein and mRNA in the hippocampus. Together, these findings suggest that OLE attenuated SPS-induced cognitive impairment significantly by inhibiting the expression of pro-inflammatory mediators in the rat brain. Thus, OLE reversed several behavioral impairments triggered by the traumatic stress of SPS and might be a potential useful therapeutic intervention for PTSD.
KeywordsOleuropein Memory Post-traumatic stress disorder Brain-derived neurotrophic factor cAMP response element-binding protein Pro-inflammatory cytokines
This research was supported by a Grant from the National Research Foundation of Korea funded by the Korean government (2016R1D1A1A09917012).
- 1.Shafia S, Vafaei AA, Samaei SA, Bandegi AR, Rafiei A, Valadan R, Hosseini-Khah Z, Mohammadkhani R, Rashidy-Pour A (2017) Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis-related proteins in a rat model of post-traumatic stress disorder. Neurobiol Learn Mem 139:165–178CrossRefGoogle Scholar
- 6.Karpova NN, Pickenhagen A, Lindholm J, Tiraboschi E, Kulesskaya N, Agústsdóttir A, Antila H, Popova D, Akamine Y, Bahi A, Sullivan R, Hen R, Drew LJ, Castrén E (2011) Fear erasure in mice requires synergy between antidepressant drugs and extinction training. Science 334:1731–1734CrossRefGoogle Scholar
- 21.Kaeidi A, Esmaeili-Mahani S, Sheibanib V, Abbasnejad M, Rasoulian B, Hajializadeh Z, Afrazi S (2011) Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies. J Ethnopharmacol 136:188–196CrossRefGoogle Scholar
- 32.Cohen RM, Rezai-Zadeh K, Weitz TM, Rentsendorj A, Gate D, Spivak I, Bholat Y, Vasilevko V, Glabe CG, Breunig JJ, Rakic P, Davtyan H, Agadjanyan MG, Kepe V, Barrio JR, Bannykh S, Szekely CA, Pechnick RN, Town T (2013) A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aβ, and frank neuronal loss. J Neurosci 33:6245–6256CrossRefGoogle Scholar
- 34.Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, vol 3. Academic Press, New York, pp 54–85Google Scholar
- 42.Peng Z, Wang H, Zhang R, Chen Y, Xue F, Nie H, Chen Y, Wu D, Wang Y, Wang H, Tan Q (2013) Gastrodin ameliorates anxiety-like behaviors and inhibits IL-1beta level and p38 MAPK phosphorylation of hippocampus in the rat model of posttraumatic stress disorder. Physiol Res 62:537–545PubMedPubMedCentralGoogle Scholar