Improved spatial learning and memory by perilla diet is correlated with immunoreactivities to neurofilament and α-synuclein in hilus of dentate gyrus

Proteome Science

Jinkyu Lim¹  Jong Sang Kim¹  Yeong Keun Yeo¹  Ju-Young Lee¹  Sunmin Park¹  Jinwoo Lee¹ 

[1] Major in Food Biomaterials, Kyungpook National University, Daegu, 702-701, South Korea

关键词: Immunohistochemistry;    2-D gel;    Proteome;    Hippocampus;    Cognition;    n-3 fatty acid;    Perilla;   

Others  :  817109
DOI  :  10.1186/1477-5956-10-72

 received in 2012-08-17, accepted in 2012-11-29,  发布年份 2012

【 摘 要 】

Background

Perilla (Perilla frutescens) oil is very rich in α-linolenic acid, an omega-3 fatty acid. As it is widely reported that omega-3 fatty acid supplementation improves cognitive function in children and adults, feeding rats with perilla diets followed by analysis of proteomic changes in the hippocampus can provide valuable information on the mechanism of learning and memory at the molecular level. To identify proteins playing roles in learning and memory, differentially expressed proteins in the hippocampus of the 5 week old rats fed perilla diets for 3 weeks or 3 months were identified by proteomic analysis and validated by immunological assays.

Results

The perilla diet groups showed improved spatial learning and memory performances in a T-maze test. They also displayed elevated level of 22:6n-3 fatty acid, an omega-3 fatty acid (p<0.05), in the brain compared to the control diet group. Quantitative proteomic analysis using 2-D gels as well as functional annotation grouping with the differentially expressed proteins in the hippocampus showed that those proteins involved in cytoskeleton and transport were the major differentially expressed proteins in the 3-week group, whereas those involved in energy metabolism, neuron projection and apoptosis in addition to cytoskeleton and transport were the major ones in the 3 month group. Differential protein expression in the hippocampus was validated by Western blotting using four selected proteins, known to be involved in synaptic plasticity; AMPA receptor, neurofilament, α-synuclein, and β-soluble NSF attachment protein. Brain sections from the perilla-diet groups showed enhanced immunoreactivities to α-synuclein and neurofilament. Especially, neurofilament immunoreactive cells manifested longer neurite projections in the hilus of dentate gyrus of the perilla-diet groups.

Conclusion

Improved cognitive function upon administration of n-3 fatty acid-rich perilla diet is associated with the differential expression of hippocampal proteins related to cytoskeleton, energy metabolism, transport, neuro-projection, and apoptosis. Particularly, the enhanced immunoreactivities to α-synuclein and neurofilament in the hilus of dentate gyrus suggest that perilla diet supplementation promotes neuronal signaling and alters synaptic plasticity for improved learning and memory.

【 授权许可】

   
2012 Lee et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Goelet P, Castellucci VF, Schacher S, Kandel ER: The long and the short of long-term memory–a molecular framework. Nature 1986, 322:419-422.
• [2]Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N: Translational control of long-lasting synaptic plasticity and memory. Neuron 2009, 61:10-26.
• [3]Jin I, Kandel ER, Hawkins RD: Whereas short-term facilitation is presynaptic, intermediate-term facilitation involves both presynaptic and postsynaptic protein kinases and protein synthesis. Learn Mem 2011, 18:96-102.
• [4]Gkogkas C, Sonenberg N, Costa-Mattioli M: Translational control mechanisms in long-lasting synaptic plasticity and memory. J Biol Chem 2010, 285:31913-31917.
• [5]Kanoski SE, Davidson TL: Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav 2011, 103:59-68.
• [6]Kennedy DO, Haskell CF: Vitamins and cognition: what is the evidence? Drugs 2011, 71:1957-1971.
• [7]Spencer JP: The impact of fruit flavonoids on memory and cognition. Br J Nutr 2010, 104(Suppl 3):S40-S47.
• [8]Karr JE, Alexander JE, Winningham RG: Omega-3 polyunsaturated fatty acids and cognition throughout the lifespan: a review. Nutr Neurosci 2011, 14:216-225.
• [9]Kitajka K, Puskas LG, Zvara A, Hackler L Jr, Barcelo-Coblijn G, Yeo YK, Farkas T: The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Natl Acad Sci U S A 2002, 99:2619-2624.
• [10]Yamamoto N, Saitoh M, Moriuchi A, Nomura M, Okuyama H: Effect of dietary alpha-linolenate/linoleate balance on brain lipid compositions and learning ability of rats. J Lipid Res 1987, 28:144-151.
• [11]Kitajka K, Sinclair AJ, Weisinger RS, Weisinger HS, Mathai M, Jayasooriya AP, Halver JE, Puskas LG: Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression. Proc Natl Acad Sci U S A 2004, 101:10931-10936.
• [12]Barcelo-Coblijn G, Kitajka K, Puskas LG, Hogyes E, Zvara A, Hackler L Jr, Farkas T: Gene expression and molecular composition of phospholipids in rat brain in relation to dietary n-6 to n-3 fatty acid ratio. Biochim Biophys Acta 2003, 1632:72-79.
• [13]Asif M: Health effects of omega-3,6,9 fatty acids: perilla frutescens is a good example of plant oils. Orient Pharm Exp Med 2011, 11:51-59.
• [14]Rao S, Abdel-Reheem M, Bhella R, McCracken C, Hildebrand D: Characteristics of high alpha-linolenic acid accumulation in seed oils. Lipids 2008, 43:749-755.
• [15]Riedel G, Platt B, Micheau J: Glutamate receptor function in learning and memory. Behav Brain Res 2003, 140:1-47.
• [16]Malinow R, Malenka RC: AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 2002, 25:103-126.
• [17]Shi L, Adams MM, Linville MC, Newton IG, Forbes ME, Long AB, Riddle DR, Brunso-Bechtold JK: Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis. Exp Neurol 2007, 206:70-79.
• [18]Calder PC: Mechanisms of action of (n-3) fatty acids. J Nutr 2012, 142:592S-599S.
• [19]Bhatia HS, Agrawal R, Sharma S, Huo YX, Ying Z, Gomez-Pinilla F: Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood. PLoS One 2011, 6:e28451.
• [20]Santos IL, Kim KS, Kim JS, Lim J: Phosphoproteomic analysis of the brain of ovariectomized adult rat. J Appl Biol Chem 2011, 54:101-107.
• [21]Winner B, Kohl Z, Gage FH: Neurodegenerative disease and adult neurogenesis. Eur J Neurosci 2011, 33:1139-1151.
• [22]Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, et al.: Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 2000, 25:239-252.
• [23]Alim MA, Hossain MS, Arima K, Takeda K, Izumiyama Y, Nakamura M, Kaji H, Shinoda T, Hisanaga S, Ueda K: Tubulin seeds alpha-synuclein fibril formation. J Biol Chem 2002, 277:2112-2117.
• [24]Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, Nicoll RA, Edwards RH: Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010, 65:66-79.
• [25]Nuber S, Petrasch-Parwez E, Winner B, Winkler J, von Horsten S, Schmidt T, Boy J, Kuhn M, Nguyen HP, Teismann P, Schulz JB, Neumann M, Pichler BJ, Reischl G, Holzmann C, Schmitt I, Bornemann A, Kuhn W, Zimmermann F, Servadio A, Riess O: Neurodegeneration and motor dysfunction in a conditional model of Parkinson's disease. J Neurosci 2008, 28:2471-2484.
• [26]Gureviciene I, Gurevicius K, Tanila H: Aging and alpha-synuclein affect synaptic plasticity in the dentate gyrus. J Neural Transm 2009, 116:13-22.
• [27]De Franceschi G, Frare E, Pivato M, Relini A, Penco A, Greggio E, Bubacco L, Fontana A, de Laureto PP: Structural and morphological characterization of aggregated species of alpha-synuclein induced by docosahexaenoic acid. J Biol Chem 2011, 286:22262-22274.
• [28]Al-Chalabi A, Miller CC: Neurofilaments and neurological disease. BioEssays 2003, 25:346-355.
• [29]Kim S, Chang R, Teunissen C, Gebremichael Y, Petzold A: Neurofilament stoichiometry simulations during neurodegeneration suggest a remarkable self-sufficient and stable in vivo protein structure. J Neurol Sci 2011, 307:132-138.
• [30]Szaro BG, Strong MJ: Post-transcriptional control of neurofilaments: New roles in development, regeneration and neurodegenerative disease. Trends Neurosci 2010, 33:27-37.
• [31]Wurtman RJ, Cansev M, Ulus IH: Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J Nutr Health Aging 2009, 13:189-197.
• [32]Gerlai R: A new continuous alternation task in T-maze detects hippocampal dysfunction in mice. A strain comparison and lesion study. Behav Brain Res 1998, 95:91-101.