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Carob (Ceratonia siliqua L.) Prevents Short-Term Memory Deficit Induced by Chronic Stress in Rats

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Abstract

Long-term exposure to stressful conditions could impair the normal brain structure and function, specifically the hippocampus-dependent memory. This impairment could be attributed to a decrease in brain-derived neurotrophic factor (BDNF) levels during chronic stress. Knowing that carob [Ceratonia siliqua L. (Fabaceae)] is rich in a wide variety of polyphenols with a high antioxidant value, we hypothesized that the methanolic carob extract (C. siliqua) pods will prevent stress-induced memory impairment. Hence, the methanolic extract of carob pods was investigated for its ability to enhance learning and memory as well as to protect from memory impairment in normal stressed animals. Rats were chronically stressed for 7 weeks via the intruder stress model. Carob extract was administered to animals via intraperitoneal (i.p.) route at a daily dose of 50 mg/kg. Radial arm water maze (RAWM) was utilized to test for spatial learning and memory. In addition, brain tissues were dissected to determine BDNF levels. Chronic stress (CS) impaired short-term spatial memory (number of committed errors: P < 0.05, days to criterion (DTC): P < 0.001). Animal treatment with carob pod extract prevented the short-term memory impairment induced by CS (P < 0.05), while such treatment showed no effect on memory functions of unstressed rats. Moreover, carob pod extract prevented the reduction in the hippocampal BDNF (P < 0.05) induced by chronic stress exposure. In conclusion, CS impaired short-term memory function, while methanolic extract of carob pods prevented this impairment, probably as a result of preventing reduction in BDNF levels in the hippocampus.

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References

  • Abu Hafsa SH, Ibrahim SA, Hassan AA (2017) Carob pods (Ceratonia siliqua L.) improve growth performance, antioxidant status and caecal characteristics in growing rabbits. J Anim Physiol Anim Nutr (Berl) 101:1307–1315

    Article  CAS  Google Scholar 

  • Agrawal A, Mohan M, Kasture S, Foddis C, Frau MA, Loi MC, Maxia A (2011) Antidepressant activity of Ceratonia siliqua L. fruit extract, a source of polyphenols. Nat Prod Res 25:450–456

    Article  CAS  Google Scholar 

  • Alali FQ, Tawaha K, El-Elimat T, Syouf M, El-Fayad M, Abulaila K, Nielsen SJ, Wheaton WD, Falkinham JO 3rd, Oberlies NH (2007) Antioxidant activity and total phenolic content of aqueous and methanolic extracts of Jordanian plants: an ICBG project. Nat Prod Res 21:1121–1131

    Article  CAS  Google Scholar 

  • Aleisa AM, Alzoubi KH, Alkadhi KA (2006a) Chronic but not acute nicotine treatment reverses stress-induced impairment of LTP in anesthetized rats. Brain Res 1097:78–84

    Article  CAS  Google Scholar 

  • Aleisa AM, Alzoubi KH, Gerges NZ, Alkadhi KA (2006b) Nicotine blocks stress-induced impairment of spatial memory and long-term potentiation of the hippocampal CA1 region. Int J Neuropsychopharmacol 9:417–426

    Article  CAS  Google Scholar 

  • Alkadhi KA, Alzoubi KH, Srivareerat M, Tran TT (2011) Chronic psychosocial stress exacerbates impairment of synaptic plasticity in beta-amyloid rat model of Alzheimer's disease: prevention by nicotine. Curr Alzheimer Res 8:718–731

    Article  CAS  Google Scholar 

  • Alnos M, Vianna M, Denino A, Mello T, Pereira P, Sqzapiro G et al (2002) BDNF-triggered events in the rat hippocampus are required for both short- and long-term memory formation. Hippocampus 12:551–560

    Article  Google Scholar 

  • Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA (2009) Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats. Behav Brain Res 204:117–123

    Article  CAS  Google Scholar 

  • Alzoubi KH, Srivareerat M, Tran TT, Alkadhi KA (2013a) Role of alpha7- and alpha4beta2-nAChRs in the neuroprotective effect of nicotine in stress-induced impairment of hippocampus-dependent memory. Int J Neuropsychopharmacol 16:1105–1113

    Article  CAS  Google Scholar 

  • Alzoubi KH, Srivareerat M, Aleisa AM, Alkadhi KA (2013b) Chronic caffeine treatment prevents stress-induced LTP impairment: the critical role of phosphorylated CaMKII and BDNF. J Mol Neurosci 49:11–20

    Article  CAS  Google Scholar 

  • Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA (2013c) Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet. Behav Brain Res 237:7–14

    Article  CAS  Google Scholar 

  • Aruoma OI, Bahorun T, Jen LS (2003) Neuroprotection by bioactive components in medicinal and food plant extracts. Mutat Res 544:203–215

    Article  CAS  Google Scholar 

  • Aubin Dakia P, Wathelet B, Paquot M (2007) Isolation and chemical evaluation of carob (Ceratonia siliqua L.) seed germ. Food Chem 102:1368–1374

    Article  Google Scholar 

  • Azab A (2017) Carob (ceratonia siliqua): health, medicine and chemistry. Eur Chem Bull 10:456–469

    Article  Google Scholar 

  • Bengoechea C, Romero A, Villanueva A, Moreno G, Alaiz M, Millán F, Guerrero A, Puppo MC (2008) Composition and structure of carob (Ceratonia siliqua L.) germ proteins. Food Chem 107:675–683

    Article  CAS  Google Scholar 

  • Biner B, Gubbuk H, Karhan M, Aksu M, Pekmezci M (2007) Sugar profiles of the pods of cultivated and wild types of carob bean (Ceratonia siliqua L.) in Turkey. Food Chem 100:1453–1455

    Article  CAS  Google Scholar 

  • Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  CAS  Google Scholar 

  • Bodnoff SR, Humphreys AG, Lehman JC, Diamond DM, Rose GM, Meaney MJ (1995) Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats. J Neurosci 15:61–69

    Article  CAS  Google Scholar 

  • Buwalda B, Kole MH, Veenema AH, Huininga M, de Boer SF, Korte SM, Koolhaas JM (2005) Long-term effects of social stress on brain and behavior: a focus on hippocampal functioning. Neurosci Biobehav Rev 29:83–97

    Article  Google Scholar 

  • Cattaneo A, Riva MA (2016) Stress-induced mechanisms in mental illness: a role for glucocorticoid signalling. J Steroid Biochem Mol Biol 160:169–174

    Article  CAS  Google Scholar 

  • Cottrell GA, Nakajima S (1977) Effect of corticosteroids in the hippocampus on passive avoidance behavior in the rat. Pharmacol Biochem Behav 7:277–280

    Article  CAS  Google Scholar 

  • de Quervain D, Schwabe L, Roozendaal B (2017) Stress, glucocorticoids and memory: implications for treating fear-related disorders. Nat Rev Neurosci 18:7–19

    Article  Google Scholar 

  • Diamond DM, Campbell A, Park CR, Vouimba RM (2004) Preclinical research on stress, memory, and the brain in the development of pharmacotherapy for depression. Eur Neuropsychopharmacol 14(Suppl 5):S491–S495

    Article  CAS  Google Scholar 

  • Gerges NZ, Alzoubi KH, Park CR, Diamond DM, Alkadhi KA (2004a) Adverse effect of the combination of hypothyroidism and chronic psychosocial stress on hippocampus-dependent memory in rats. Behav Brain Res 155:77–84

    Article  Google Scholar 

  • Gerges NZ, Alzoubi KH, Park CR, Diamond DM, Alkadhi KA (2004b) Adverse effect of the combination of hypothyroidism and chronic psychosocial stress on hippocampus-dependent memory in rats. Behav Brain Res 155:77–84

    Article  Google Scholar 

  • Gooney M, Shaw K, Kelly A, O'Mara SM, Lynch MA (2002) Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor. Behav Neurosci 116:455–463

    Article  CAS  Google Scholar 

  • Ivanco TL, Racine RJ (2000) Long-term potentiation in the reciprocal corticohippocampal and corticocortical pathways in the chronically implanted, freely moving rat. Hippocampus 10:143–152

    Article  CAS  Google Scholar 

  • Karisetty BC, Joshi PC, Kumar A, Chakravarty S (2017) Sex differences in the effect of chronic mild stress on mouse prefrontal cortical BDNF levels: a role of major ovarian hormones. Neuroscience 356:89–101

    Article  CAS  Google Scholar 

  • Kiprianova I, Freiman TM, Desiderato S, Schwab S, Galmbacher R, Gillardon F, Spranger M (1999) Brain-derived neurotrophic factor prevents neuronal death and glial activation after global ischemia in the rat. J Neurosci Res 56:21–27

    Article  CAS  Google Scholar 

  • Klenow S, Glei M, Haber B, Owen R, Pool-Zobel BL (2008) Carob fibre compounds modulate parameters of cell growth differently in human HT29 colon adenocarcinoma cells than in LT97 colon adenoma cells. Food Chem Toxicol 46:1389–1397

    Article  CAS  Google Scholar 

  • Lam WY, Bhattacharya D (2018) Metabolic links between plasma cell survival, secretion, and stress. Trends Immunol 39:19–27

    Article  CAS  Google Scholar 

  • Mazumder AG, Sharma P, Patial V, Singh D (2017) Ginkgo biloba L. attenuates spontaneous recurrent seizures and associated neurological conditions in lithium-pilocarpine rat model of temporal lobe epilepsy through inhibition of mammalian target of rapamycin pathway hyperactivation. J Ethnopharmacol 204:8–17

    Article  CAS  Google Scholar 

  • Molteni R, Barnard RJ, Ying Z, Roberts CK, Gomez-Pinilla F (2002) A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112:803–814

    Article  CAS  Google Scholar 

  • Mu JS, Li WP, Yao ZB, Zhou XF (1999) Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res 835:259–265

    Article  CAS  Google Scholar 

  • Ness D, Calabrese P (2016) Stress effects on multiple memory system interactions. Neural Plast 2016:4932128

    Article  Google Scholar 

  • Park CR, Campbell AM, Diamond DM (2001) Chronic psychosocial stress impairs learning and memory and increases sensitivity to yohimbine in adult rats. Biol Psychiatry 50:994–1004

    Article  CAS  Google Scholar 

  • Rtibi K, Selmi S, Jabri M-A, El-Benna J, Amri M, Marzouki L, Sebai H (2016) Protective effect of Ceratonia siliqua L. against a dextran sulfate sodium-induced alterations in liver and kidney in rat. J Med Food 19:882–889

    Article  Google Scholar 

  • Rtibi K, Selmi S, Grami D, Amri M, Eto B, El-Benna J, Sebai H, Marzouki L (2017) Chemical constituents and pharmacological actions of carob pods and leaves (Ceratonia siliqua L.) on the gastrointestinal tract: a review. Biomed Pharmacother 93:522–528

    Article  CAS  Google Scholar 

  • Schwabe L, Dalm S, Schachinger H, Oitzl MS (2008) Chronic stress modulates the use of spatial and stimulus-response learning strategies in mice and man. Neurobiol Learn Mem 90:495–503

    Article  Google Scholar 

  • Shawakfeh K (2005) Pod characteristics of two Ceratonia siliqua L. varieties from Jordan. Ital J Food Sci 17:187–194

    CAS  Google Scholar 

  • Shohayeb B, Diab M, Ahmed M, Ng DCH (2018) Factors that influence adult neurogenesis as potential therapy. Transl Neurodegener 7:4

    Article  Google Scholar 

  • Silanikove N, Landau S, Or D, Kababya D, Bruckental I, Nitsan Z (2006) Analytical approach and effects of condensed tannins in carob pods (Ceratonia siliqua) on feed intake, digestive and metabolic responses of kids. Livest Sci 99:29–38

    Article  Google Scholar 

  • Smith MA, Cizza G (1996) Stress-induced changes in brain-derived neurotrophic factor expression are attenuated in aged Fischer 344/N rats. Neurobiol Aging 17:859–864

    Article  CAS  Google Scholar 

  • Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15:1768–1777

    Article  CAS  Google Scholar 

  • Srivareerat M, Tran TT, Alzoubi KH, Alkadhi KA (2009a) Chronic psychosocial stress exacerbates impairment of cognition and long-term potentiation in beta-amyloid rat model of Alzheimer's disease. Biol Psychiatry 65:918–926

    Article  CAS  Google Scholar 

  • Srivareerat M, Tran TT, Alzoubi KH, Alkadhi KA (2009b) Chronic psychosocial stress exacerbates impairment of cognition and long-term potentiation in beta-amyloid rat model of Alzheimer's disease. Biol Psychiatry 65:918–926

    Article  CAS  Google Scholar 

  • Veerendra Kumar MH, Gupta YK (2002) Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats. J Ethnopharmacol 79:253–260

    Article  CAS  Google Scholar 

  • Weinreb O, Mandel S, Amit T, Youdim MB (2004) Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases. J Nutr Biochem 15:506–516

    Article  CAS  Google Scholar 

  • Wolf OT, Atsak P, de Quervain DJ, Roozendaal B, Wingenfeld K (2016) Stress and memory: a selective review on recent developments in the understanding of stress hormone effects on memory and their clinical relevance. J Neuroendocrinol 28

  • Xu H, Luo C, Richardson JS, Li XM (2004) Recovery of hippocampal cell proliferation and BDNF levels, both of which are reduced by repeated restraint stress, is accelerated by chronic venlafaxine. Pharmacogenomics J 4:322–331

    Article  CAS  Google Scholar 

  • Zhou X, Qi Y, Chen T (2017) Long-term pre-treatment of antioxidant Ginkgo biloba extract EGb-761 attenuates cerebral-ischemia-induced neuronal damage in aged mice. Biomed Pharmacother 85:256–263

    Article  CAS  Google Scholar 

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Funding

Support for this work was provided from “the Deanship of Research, Jordan University of Science and Technology, Irbid, Jordan” (Grant No. 73/2008).

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Author notes

  1. Feras Q. Alali is on leave from Jordan University of Science and Technology.

Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Karem H. Alzoubi

  2. Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Sanaa Alibbini & Tamam El-Elimat

  3. Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Omar F. Khabour

  4. Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA

    Mohammad Al-zubi

  5. College of Pharmacy, Qatar University, Doha, 2713, Qatar

    Feras Q. Alali

Authors
  1. Karem H. Alzoubi
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  2. Sanaa Alibbini
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  3. Omar F. Khabour
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  4. Tamam El-Elimat
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  5. Mohammad Al-zubi
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  6. Feras Q. Alali
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Correspondence to Feras Q. Alali.

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The study protocol was approved by the Institutional Animal Care and Use Committee at JUST.

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Alzoubi, K.H., Alibbini, S., Khabour, O.F. et al. Carob (Ceratonia siliqua L.) Prevents Short-Term Memory Deficit Induced by Chronic Stress in Rats. J Mol Neurosci 66, 314–321 (2018). https://doi.org/10.1007/s12031-018-1161-8

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  • DOI: https://doi.org/10.1007/s12031-018-1161-8

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