Beneficial effect of Boswellia serrata gum resin on spatial learning and the dendritic tree of dentate gyrus granule cells in aged rats

Document Type : Original Research Article


Department of Biology and Anatomical Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


Objective: The hippocampal formation, particularly the dentate gyrus (DG), shows age-related morphological changes that could cause memory decline. It is indicated that Boswellia resins attenuates memory deficits and the major component of Boswellia serrata (Bs) gum resin, beta boswellic acid increased neurite outgrowth and branching in hippocampal neurons. This study was designed to investigate the effect of Boswellia treatment on spatial learning performance and the morphology of dentate granule cells in aged rats.
Materials and Methods: Sixteen male Wistar rats (24 months old) were divided into experimental and control groups. Experimental group was intragastrically administered with the aqueous extract of Bs (100 mg/kg/d for 8 weeks) and control group received a similar volume of water. Spatial learning performance of rats was tested using Morris water maze task. At the end of experiment, the brain was removed and the right hippocampus was serially sectioned for morphometric analysis. The Cavalieri principle was employed to estimate the volume of the DG. A quantitative Golgi study was used to analyze the dendritic trees of dentate granule cells.
Results: Chronic treatment with Bs improved spatial learning capability during the three acquisition days. Comparisons also revealed that Bs-treated aged rat had greater DG with increased dendritic complexity in the dentate granule cells than control rats. Hippocampal granule cells of Bs-treated aged rats had more dendritic segments, larger arbors, more numerical branching density and more dendritic spines in comparison to control animals.
Conclusion: This study provided a neuro-anatomical basis for memory improvement due to chronic treatment with Bs.


Main Subjects

Bailey CH, Kandel E. 2008. Synaptic remodeling, synaptic growth and the storage of long-term memory in Aplysia. Prog Brain Res, 169: 179-198.
Butz M, Worgotter F, van Ooyen A. 2009. Activity-dependent structural plasticity. Brain Res Rev, 60: 287-305.
Cameron HA, Gould E. 1995. The control of neuronal birth and survival. In: Shaw CA, Ed. Receptor Dynamics in Neural Development. pp. 141-57. New York: CRC Press.
De Ruiter JP, Uylings HBM. 1987. Morphometric and dendritic analysis of fascia dentata granule cells in human aging and senile dementia. Brain Res, 402: 217-229.
Duwiejua M, Zeitlin IJ,Waterman PG, Chapman J. 1993. Anti-inflammatory activity of resins from some species of the plant familyBurseracea. Planta Med, 59: 6-12.
Farshchi A, Ghiasi G, Farshchi S, MalekKhatabi P. 2010. Effects of BoswelliaPapyrifera Gum Extract on Learning and Memory in Mice and Rats. Iran J Basic Med Sci, 13: 9-15.
Gabbott PL, Somogyi J. 1994. The ‘single’ section Golgi impregnation procedure: Methodological description. J Neurosci Methods, 11: 221-230.
Geinisman Y, deToledo-Morrell L, Morrell F, Persina IS, Rossi M. 1992. Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological disector technique. Hippocampus, 2: 437-444.
Geinisman Y, Bondareff w, Dodge JT. 1978. Dendritic atrophy in the dentate gyrus of the senescent rat. Am J Anat, 152: 321-9.
Geinisman Y, Bondareff w, Dodge JT. 1977.  Partial deafferentation of neurons in the dentate gyrus of the senescent rat. Brain Res, 134:541-545.
Gundersen HJG, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, , Nyengaard JR, Pakkenberg B, Sørensen FB, Vesterby A, West MJ. 1988. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS, 96: 379-394.
Himeda T, Mizuno K, Kato H, Araki T. 2005. Effects of age on immunohistochemical changes in the mouse hippocampus. Mech Ageing Dev, 126: 673-677.
Hosseini M, Hadjzad M, Derekhshan M, Havakhah S, Rassouli FB, Rakhshandeh H, Saffarzadeh F. 2010. The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze. Arch Pharm Res, 33: 463-468.
Karima O, Riazi G, Khodadadi S, Yousefi R, Mahnam K, Mokhtari F, Cheraghi T, Hoveizi E, Moosavi-Movahedi AA. 2012. An in vitro study of the role of β-boswellic acid in the microtubule assembly dynamics. FEBS Lett, 586: 4132-4138.
Karima O, Riazi G, Yousefi R, MoosaviMovahedi AA. 2010. The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study). Neurol Sci, 31: 315-320.
Luebke JI, Rosene DL. 2003. Aging alters dendritic morphology, input resistance, and inhibitory signaling in dentate granule cells of the rhesus monkey. J Comp Neurol, 460: 573-584.
Mahmoudi A, Hosseini-Sharifabad A, Monsef-Esfahani HR, Yazdinejad AR, Khanavi M, Roghani A, Beyer C, Sharifzadeh M. 2011. Evaluation of systemic administration of Boswelliapapyrifera extracts on spatial memory retention in male rats. J Nat Med, 65: 519-525.
Manikandan S1, Padma MK, Srikumar R, JeyaParthasarathy N, Muthuvel A, Sheela Devi R. 2006. Effects of chronic noise stress on spatial memory of rats in relation to neuronal dendritic alteration and free radical-imbalance in hippocampus and medial prefrontal cortex. Neurosci Lett, 399:17-22.
Menon MK, Kar A. 1971. Analgesic and psychopharmacological effects of the gum resin of Boswellia serrata. Planta Med, 19: 333-341.
Morris RGM. 1984. Developments of a water–maze procedure for studying spatial learning in the rat. J Neurosci Methods, 11: 47-60.
Mothana RA, Lindequist U, Gruenert R, Bednarski PJ. 2009. Studies of the in vitro anticancer, antimicrobial and antioxidant potentials of selected Yemeni medicinal plants from the island Soqotra. BMC Complement Altern Med, 9: 7.
Moussaieff A, Mechoulam R. 2009. Boswellia resin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials. J Pharm Pharmacol, 61: 1281-1293.
Moussaieff A, Shein NA, Tsenter J, Grigoriadis S, Simeonidou C, Alexandrovich AG, Trembovler V, Ben-Neriah Y, Schmitz ML, Fiebich BL, Munoz E, Mechoulam R, Shohami E. 2008a. Incensole acetate-a novel neuroprotective agent isolated from Boswelliacarterii. J Cereb Blood Flow Metab, 28: 1341-1352.
Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, Kashman Y, Huang SM, Lee H, ShohamiE, Mackie K, Caterina MJ, Walker JM, Fride E, Mechoulam R. 2008b. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. FASEB J, 22: 3024-3034.
Nemat AZY, Siham MA, Karam AM, Nadia AMG, Abd El-Fattah HM, Abdel Razik, HF, Bassant MMI. 2013. Effect of Boswelliaserrata on Alzheimer’s disease induced in rats. J Arab Soc Med Res, 8: 1-11.
Purves D. 1988. Regulation of neural connections in maturity. In body and brain, A trophic theory of neural connections. pp. 2505-2511, Harvard Univ press; Cambridge.
Ramírez-Amaya V, Escobar ML, Chao V, Bermúdez-Rattoni F. 1999.Synaptogenesis of mossy fibers induced by spatial water maze overtraining. Hippocampus, 9: 631-636.
Reul JM, De Kloet ER. 1985. Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation. Endocrinology, 117: 2505-2511.
Rusakov DA, Davies HA, Harrison E, Diana G, Richter-Levin G, Bliss TV, Stewart MG. 1997. Ultrastructural synaptic correlates of spatial learning in rat hippocampus. Neuroscience, 80: 69-77.
Safayhi H, Ammon HPT. 1997. PharmakologischeAspecte von Weihrauch und Boswelliasauren. Pharm Z, 142: 3277-3286.
Salas-Ramirez KY, Frankfurt M, Alexander A, Luine VN, Friedman E. 2010. Prenatal cocaine exposure increases anxiety, impairs cognitive function and increases dendritic spine density in adult rats: Influence of sex Neuroscience, 169: 1287-1295.
Sapolsky RM. 1999. Glucocorticoids, stress and their adverse neurological effects: Relevance to aging. Exp Gerontol, 34: 721-732.
Scharfman H. 2007. The dentate gyrus: a comprehensive guide to structure, function, and clinical implications. Amsterdam: Elsevier.
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.
Uemura E, Carriquiry A, Kliemann W, Goodwin J. 1995. Mathematicalmodeling of dendritic growth in vitro. Brain Res, 671: 187-194.
Uylings HB, Van Pelt J. 2002. Measures for quantifying dendritic arborizations. Network, 13: 397-414.
Valladolid-Acebes I, Fole A, Martín M, Morales L, Cano MV, Ruiz-Gayo M, Del Olmo N. 2013. Spatial memory impairment and changes in hippocampal morphology are triggered by high-fat diets in adolescent mice. Is there a role of leptin? Neurobiol Learn Mem, 106:18-25.
Von Bohlen und Halbach O, Zacher C, Gass P, Unsicker K. 2006. Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice. J Neurosci Res, 83: 525-531.