Alterations in neuronal morphology and synaptophysin expression in the rat brain as a result of changes in dietary n-6: n-3 fatty acid ratios

Lipids in Health and Disease

Mahdi Ebrahimi²  Tan Ai Li²  Sharmili Vidyadaran¹  Mohamed Ali Rajion²  Yong Meng Goh³  Toktam Hajjar² 

[1] Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia;Department of Veterinary Preclinical Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia;Institute of Tropical Agriculture, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

关键词: Rats;    Hippocampus;    Synaptophysin;    Neuronal morphology;    n-3 polyunsaturated fatty acid;   

Others  :  834227
DOI  :  10.1186/1476-511X-12-113

 received in 2013-03-28, accepted in 2013-07-24,  发布年份 2013

【 摘 要 】

Background

Polyunsaturated fatty acids (PUFA) play important roles in brain fatty acid composition and behavior through their effects on neuronal properties and gene expression. The hippocampus plays an important role in the formation of memory, especially spatial memory and navigation. This study was conducted to examine the effects of PUFA and specifically different dietary n-6: n-3 fatty acid ratios (FAR) on the number and size of hippocampal neurons and the expression of synaptophysin protein in the hippocampus of rats.

Methods

Forty 3-week old male Sprague–Dawley rats were allotted into 4 groups. The animals received experimental diets with different n-6: n-3 FAR of either 65:1, 26.5:1, 22:1 or 4.5:1 for 14 weeks.

Results

The results showed that a lowering dietary n-6: n-3 FAR supplementation can increase the number and size of neurons. Moreover, lowering the dietary n-6: n-3 FAR led to an increase in the expression of the pre-synaptic protein synaptophysin in the CA1 hippocampal subregion of the rat brain.

Conclusions

These findings support the notion that decreasing the dietary n-6: n-3 FAR will lead to an intensified hippocampal synaptophysin expression and increased neuron size and proliferation in the rat brain.

【 授权许可】

   
2013 Hajjar et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, et al.: Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 1999, 23:247-256.
• [2]Sydow A, Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, et al.: Tau- induced defects in synaptic plasticity, learning and memory are revisable in transgenic mice after switching off the toxic tau mutant. Neuroscience 2011, 31(7):2511-2525.
• [3]Kesner RP, Lee I, Gilbert P: A behavioral assessment of hippocampal function based on a subregional analysis. Rev Neurosci 2004, 15:333-351.
• [4]Barton RA: Neocortex size and behavioural ecology in primates. Proc R Soc London B 1996, 263:173-177.
• [5]Gould E, Beylin A, Tanapat P, Reeves A, Shors T: Learning enhances adult neurogenesis in the hippocampal formation. Natl Neurosci 1999, 2:260-265.
• [6]Magarinos A, McEwen B, Flugge G, Fuchs E: Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neuro 1996, 16:3534-3540.
• [7]Bliss T, Collingridge GA: Synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993, 361:31-39.
• [8]McQuade JMS: The involvement of DFF45 and c-Fos in hippocampal plasticity and function. USA: University of Cincinnati; 2002. [PhD thesis]
• [9]Weimer RM, Jorgensen EM: Controversies in synaptic vesicle exocytosis. J Cell Sci 2003, 116:3661-3666.
• [10]Counts SE, Nadeem M, Lad SP, Wuu J, Mufson EJ: Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment. J Neuropathol Exp Neurol 2006, 65:592-601.
• [11]Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell JW, et al.: Differential loss of synaptic proteins in Alzheimer’s disease: implications for synaptic dysfunction. J Alzheimers Dis 2005, 7(2):103-117.
• [12]Solfrizzi V, Colacicco AM, D’Introno A, Capurso C, Torres F, Rizzo C, et al.: Dietary intake of unsaturated fatty acids and age-related cognitive decline: a 8.5-year follow-up of the Italian longitudinal study on aging. Neurobiol Aging 2006, 27:1694-1704.
• [13]Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R: PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology 2009, 34:199-211.
• [14]Su HM: Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. J Nutr Biochem 2010, 21(5):364-373.
• [15]Coti B, O’Kusky J, Innis SM: Maternal dietary n-3 fatty acid deficiency alters neurogenesis in the embryonic rat brain. J Nutr 2006, 36:1570-1575.
• [16]Cao DH, Xu JF, Xue RH, Zheng WF, Liu ZL: Protective effect of chronic ethyl docosaehxaenoate administration on brain injury in ischemic gerbils. Pharmacol Biochem Behav 2004, 79:651-659.
• [17]Ahmad A, Moriguchi T, Salem N: Decrease in neuron size in docosahexaenoic acid- deficient brain. Pediatr Neurol 2002, 26(3):210-218.
• [18]Gustilo M, Markowska A, Breckler S, Fleischman C, Price D, Koliatsos V: Evidence that nerve growth factor influences recent memory through structural changes in septohippocampal cholinergic neurons. J Comp Neurol 1999, 405:491-507.
• [19]Giraud MN, Motta C, Boucher D, Grizard G: Membrane fluidity predicts the outcome of cryopreservation of human spermatozoa. Hum Reprod 2000, 15:2160-2164.
• [20]Fukaya T, Gondaira T, Kashiyae Y, Kotani S, Ishikura Y, Fujikawa S, et al.: Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats. Neurobiol Aging 2007, 28:1179-1186.
• [21]Okaichi Y, Ishikura Y, Akimoto K, Kawashima H, Toyoda-Ono Y, Kiso Y, Okaichi H: Arachidonic acid improves aged rats’ spatial cognition. Physiol Behav 2005, 84:617-623.
• [22]Uauy R, Danqour AD: Nutrition in brain development and aging: role of essential fatty acids. Nutr Rev 2006, 64:524-533.
• [23]Innis SM: Dietary omega 3 fatty acids and the developing brain. Review Literature Arts Americas 2008, 1237:35-43.
• [24]Ikemoto A, Nitta A, Furukawa S: Dietary n-3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus. Neurosci Lett 2000, 285:99-102.
• [25]Hajjar T, Goh YM, Rajion MA, Vidyadaran S, Othman F, Farjam AS, Ebrahimi M: Omega 3 polyunsaturated fatty acid improves spatial learning and hippocampal Peroxisome Proliferator Activated Receptors (PPARα and PPARγ) gene expression in rats. BMC Neurosci 2012, 13(1):109. BioMed Central Full Text
• [26]Bourre JM: Fatty acids, cognition, behavior, brain development, and mood diseases. In Fatty acids in foods and their health implication. 3rd edition. New York: Marcel Dekker, Inc; 2007:935-954.
• [27]Das UN: Can memory be improved? A discussion on the role of ras, GABA, acetylcholine, NO, insulin, TNF-a, and long-chain polyunsaturated fatty acids in memory formation and consolidation. Brain Dev 2003, 25:251-261.
• [28]Chalon S: Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 2006, 75:259-269.
• [29]Igarashi M, Ma K, Chang L, Bell JM, Rapoport SI: Rat heart cannot synthesize docosahexaenoic acid from circulating alpha -linolenic acid because it lacks elongase-2. Lipid Res 2008, 49:1735-1745.
• [30]Hasselmo ME: Neuromodulation: acetylcholine and memory consolidation. Trends Cogn Sci 1999, 3:351-359.
• [31]Lauritzen L, Hansen HS, Jørgensen MH, Michaelsen KF: The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001, 40(1–2):1-94.
• [32]Borovikova LV, Ivanova S, Zhang M: Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000, 405:458.
• [33]Anna R, Carta Pisanu A: Modulating Microglia activity with PPAR-γ Agonists: a promising therapy for Parkinson’s disease? Neurotox Res 2013, 23(2):112-123.
• [34]Sun Y, Alexander SPH, Kendall DA, Bennett AJ: Cannabinoids and PPARa signalling. Biochem Soc Trans 2006, 34(6):1095-1097.
• [35]Zahra FH, Tasker RA: Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) activation confers functional Neuroprotection in Global Ischemia. Neurotoxicity Res 2011, 19(3):462-471.
• [36]Wainwright PE, Huang YS, Bulman-Fleming B, Dalby D, Mills DE, Redden P, McCutcheon D: The effects of dietary n-3/n-6 ratio on brain development in the mouse: a dose response study with long-chain n-3 fatty acids. Lipids 1992, 27(2):98-103.
• [37]Stevens LJ, Zentall SS, Abate ML: Omega-3 fatty acids in boys with behavior, learning and health problems. Physiol Behav 1996, 59:915-920.
• [38]Willats P, Forsyth JS, DiModugno MK: Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet 1998, 352:688-691.
• [39]Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, et al.: Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 2006, 56:159-164.
• [40]Yehuda S: Omega – 6/Omega – 3 Ratio and brain-related functions. World Rev Nutr Diet 2003, 92:37-56.
• [41]Champeil-Potokar G, Denis I, Goustard-Langelier B, Alessandri JM, Guesnet P, Lavialle M: Astrocytes in culture require docosahexaenoic acid to restore the n-3/n-6 polyunsaturated fatty acid balance in their membrane phospholipids. J Neurosci Res 2004, 75:96-106.
• [42]Hoffman PN, Griffin JW, Koo EH, Muma NA, Price DL: Neurofilaments, axonal caliber, perikaryal size. In Aging and the brain. Edited by Terry RD. New York: Raven Press; 1988:205-217.
• [43]Garofalo L, Ribeiro-da-Silva A, Cuello AC: Nerve growth factorinduced synaptogenesis and hypertrophy of cortical cholinergic terminals. Proc Natl Acad Sci USA 1992, 89:2639-2643.
• [44]Purves D, Snider WD, Voyvodic JT: Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system. Nature 1988, 336:123-128.
• [45]Smith TD, Adams MM, Gallagher M, Morrison JH, Rapp R: Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. Neuroscience 2000, 20(17):6587-6593.
• [46]Martin DS, Spencer P, Horrobin DF, Lynch MA: Long-term potentiation in aged rats is restored when the age-related decrease in polyunsaturated fatty acid concentration is reversed. Prostaglandins Leukot Essent Fatty Acids 2002, 67:121-130.
• [47]Hama H, Hara C, Yamaguchi K, Miyawaki A: PKC signaling mediates global enhancement of excitatory synaptogenesis in nerons triggered by local contact with astrocytes. Neuron 2004, 41:405-415.
• [48]Corriveau RA: Electrical activity and gene expression in the development of vertebrate neural circuits. J Neurobiol 1999, 41:148-157.
• [49]Wu A, Ying Z, Gomez-Pinilla F: Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 2008, 1553:751-759.
• [50]Janz R, Sudhof TC, Hammer RE, Unni V, Siegelbaum SA, Bolshakov VY: Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 1999, 24:687-700.
• [51]Bate C, Tayebi M, Salmona M, Diomede L, Williams A: Polyunsaturated fatty acids protect against prion-mediated synapse damage in vitro. Neurotox Res 2010, 17:203-214.
• [52]Folch J, Lees M, Sloane Stanely GH: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226:497-509.
• [53]Ebrahimi M, Rajion MA, Goh YM, Sazili AQ, Schonewille JT: Effect of linseed oil dietary supplementation on fatty acid composition and gene expression in adipose tissue of growing goats. Biomed Res Int 2013, 2013:1-11.
• [54]Paxinos G, Watson C: The rat brain in stereotaxic coordinates. London: Academic; 1986.