View More View Less
  • 1 Selcuk University Department of Physiology, Meram Medical School Konya Turkey
Restricted access

The aim of this study was to examine effects of pinealectomy and melatonin administration plasma leptin levels and its relationship with zinc in rats. The study was conducted on 40 adult male Sprague-Dawley rats. They were divided into four groups each containing 10 animals. Group 1 served as control. Group 2 was pinealectomized group. Animals in Group 3 were pinealectomized and injected with melatonin (3 mg/kg/day, ip). Group 4 received melatonin alone (3 mg/kg/day, ip). At the end of the experiments, all animals were decapitated and trunk blood collected. Plasma leptin and zinc levels were determined by radioimmunoassay and Atomic Absorption Spectrophotometer methods, respectively. Although mean weights of the animals at the beginning were not significantly different among the groups, the mean weight of the pinealectomized group was found to be significantly lower than all other groups at the end of a six-month period (p < 0.01). Plasma leptin and zinc levels were the highest in melatonin-administered group (group 4; p < 0.01). The lowest plasma leptin and zinc levels were obtained in the pinealectomized group (group 2; p < 0.01). Changes in these two parameters were not statistically significant in groups 1 and 3. Our findings indicate that pinealectomy results in a decrease in leptin and zinc levels in rats, and that melatonin administration to pinealectomized rats prevents the decrease in the these parameters. In addition, long-term administration of melatonin to rats leads to an increase in both leptin and zinc concentrations.

  • Alonso-Vale, M. I., Anhe, G. F., Borges-Silva, C. N., Andreotti, S., Peres, S. B., Cipolla-Neto, J., Lima, F. B. (2004) Pinealectomy alters adipose tissue adaptability to fasting in rats. Metabolism 53 , 500–506.

    Lima F. B. , 'Pinealectomy alters adipose tissue adaptability to fasting in rats ' (2004 ) 53 Metabolism : 500 -506.

    • Search Google Scholar
  • Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J. P., Bortoluzzi, M. N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y., Lewin, M. J. (1998) The stomach is a source of leptin. Nature 394 , 790–793.

    Lewin M. J. , 'The stomach is a source of leptin ' (1998 ) 394 Nature : 790 -793.

  • Baltaci, A. K., Mogulkoc, R., Bediz, C. S., Kul, A., Ugur, A. (2003) Pinealectomy and zinc deficiency have opposite effects on thyroid hormones in rats. Endocr. Res. 29 , 473–481.

    Ugur A. , 'Pinealectomy and zinc deficiency have opposite effects on thyroid hormones in rats ' (2003 ) 29 Endocr. Res. : 473 -481.

    • Search Google Scholar
  • Baltaci, A. K., Mogulkoc, R., Kul, A., Bediz, C. S., Ugur, A. (2004) Opposite effects of zinc and melatonin on thyroid hormones in rats. Toxicology 195 , 69–75.

    Ugur A. , 'Opposite effects of zinc and melatonin on thyroid hormones in rats ' (2004 ) 195 Toxicology : 69 -75.

    • Search Google Scholar
  • Baydas, G., Gursu, F., Canpolat, S., Konar, V., Yasar, A., Canatan, H., Kelestimur, H. (2001) Effects of pinealectomy on the circadian release pattern of leptin in male rat. Neuroendocrinol. Lett. 22 , 449–452.

    Kelestimur H. , 'Effects of pinealectomy on the circadian release pattern of leptin in male rat ' (2001 ) 22 Neuroendocrinol. Lett. : 449 -452.

    • Search Google Scholar
  • Bediz, C. S., Baltaci, A. K., Mogulkoc, R. (2003) Both zinc deficiency and supplementation affect plasma melatonin levels in rats. Acta. Physiol. Hung. 90 , 353–359.

    Mogulkoc R. , 'Both zinc deficiency and supplementation affect plasma melatonin levels in rats ' (2003 ) 90 Acta. Physiol. Hung. : 353 -359.

    • Search Google Scholar
  • Bribiescas, R. G. (2003) Effects of oral zinc supplementation on serum leptin levels in ache males of eastern Paraguay. Am. J. Hum. Biol. 15 , 681–687.

    Bribiescas R. G. , 'Effects of oral zinc supplementation on serum leptin levels in ache males of eastern Paraguay ' (2003 ) 15 Am. J. Hum. Biol. : 681 -687.

    • Search Google Scholar
  • Canpolat, S., Sandal, S., Yilmaz, B., Yasar, A., Kutlu, S., Baydas, G., Kelestimur, H. (2001) Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat. Eur. J. Pharmacol. 428 , 145–148.

    Kelestimur H. , 'Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat ' (2001 ) 428 Eur. J. Pharmacol. : 145 -148.

    • Search Google Scholar
  • Chehab, F., Lim, M., Lu, R. (1996) Correction of sterility defect in homozygous obese female mice treated with human recombinant leptin. Nat. Genet. 12 , 318–320.

    Lu R. , 'Correction of sterility defect in homozygous obese female mice treated with human recombinant leptin ' (1996 ) 12 Nat. Genet. : 318 -320.

    • Search Google Scholar
  • Chen, M. D., Lin, P. Y. (2000) Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion. Obes. Res. 8 , 525–529.

    Lin P. Y. , 'Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion ' (2000 ) 8 Obes. Res. : 525 -529.

    • Search Google Scholar
  • Chen, M. D., Song, Y. M., Lin, P. Y. (2000) Zinc may be a mediator of leptin production in humans. Life Sci. 66 , 214–219.

    Lin P. Y. , 'Zinc may be a mediator of leptin production in humans ' (2000 ) 66 Life Sci. : 214 -219.

    • Search Google Scholar
  • Collins, S., Kuhn, C. M., Petro, A. E., Swick, A. G., Chrunyk, B. A., Surwit, R. S. (1996) Role of leptin in fat regulation. Nature 380 , 677.

    Surwit R. S. , 'Role of leptin in fat regulation ' (1996 ) 380 Nature : 677 -.

  • Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., José, F., Caro, J. F. (1996) Serum immunoreactive-Leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334 , 292–295.

    Caro J. F. , 'Serum immunoreactive-Leptin concentrations in normal-weight and obese humans ' (1996 ) 334 N. Engl. J. Med. : 292 -295.

    • Search Google Scholar
  • Emilsson, V., Liu, Y. L., Cawthorne, M. A., Morton, N. M., Davenport, M. (1997) Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46 , 313–316.

    Davenport M. , 'Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion ' (1997 ) 46 Diabetes : 313 -316.

    • Search Google Scholar
  • Fraker, P. J., Jardieu, P., Cook, J. (1987) Zinc deficiency and immune function. Arch. Dermatol. 123 , 1699–1701.

    Cook J. , 'Zinc deficiency and immune function ' (1987 ) 123 Arch. Dermatol. : 1699 -1701.

  • Gainsford, T., Wilson, T. A., Metcalf, D., Handman, E., McFarlane, C., Ng, A., Nicola, N. A., Alexander, W. S., Hilton, D. J. (1996) Leptin can induce proliferation, differentiation and functional activation of hemopoietic cells. Proc. Natl. Acad. Sci. U.S.A. 93 , 14564–14568.

    Hilton D. J. , 'Leptin can induce proliferation, differentiation and functional activation of hemopoietic cells ' (1996 ) 93 Proc. Natl. Acad. Sci. U.S.A. : 14564 -14568.

    • Search Google Scholar
  • Jahnke, G., Marr, M., Myers, C., Wilson, R., Travlos, G., Price, C. (1999) Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol. Sci. 50 , 271–279.

    Price C. , 'Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats ' (1999 ) 50 Toxicol. Sci. : 271 -279.

    • Search Google Scholar
  • Johnson, S. (2001) Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson’s disease? Med. Hypotheses 56 , 641–645.

    Johnson S. , 'Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson’s disease? ' (2001 ) 56 Med. Hypotheses : 641 -645.

    • Search Google Scholar
  • Kamohara, S., Burcelin, R., Halas, J. L., Friedman, J. M., Charron, M. J. (1997) Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389 , 374–377.

    Charron M. J. , 'Acute stimulation of glucose metabolism in mice by leptin treatment ' (1997 ) 389 Nature : 374 -377.

    • Search Google Scholar
  • Kuszak, J., Rodin, M. (1977) A new technique of pinealectomy for adult rats. Experientia 33 , 283–284.

    Rodin M. , 'A new technique of pinealectomy for adult rats ' (1977 ) 33 Experientia : 283 -284.

    • Search Google Scholar
  • Lord, G. M., Matarese, G., Howard, J. K., Baker, R. J., Bloom, S. R., Lechler, R. I. (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394 , 897–901.

    Lechler R. I. , 'Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression ' (1998 ) 394 Nature : 897 -901.

    • Search Google Scholar
  • Mangian, H. F., Lee, R. G., Paul, G. L., Emmert, J. L., Shay, N. F. (1998) Zinc deficiency suppresses plasma leptin concentrations in rats. J. Nutr. Biochem. 9 , 47–51.

    Shay N. F. , 'Zinc deficiency suppresses plasma leptin concentrations in rats ' (1998 ) 9 J. Nutr. Biochem. : 47 -51.

    • Search Google Scholar
  • Mantzoros, C. S., Flier, J. S., Rogol, A. D. (1997) A longitudinal assessment of hormonal and physical alterations during normal puberty in boys: rising leptin levels may signal the onset of puberty. J. Clin. Endocrinol. Metab. 82 , 1065–1070.

    Rogol A. D. , 'A longitudinal assessment of hormonal and physical alterations during normal puberty in boys: rising leptin levels may signal the onset of puberty ' (1997 ) 82 J. Clin. Endocrinol. Metab. : 1065 -1070.

    • Search Google Scholar
  • Mastronardi, C. A., Walczewska, A., Yu, W. H., Karanth, S., Parlow, A. F., McCann, S. M. (2000) The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. Proc. Soc. Exp. Biol. Med. 224 , 152–158.

    McCann S. M. , 'The possible role of prolactin in the circadian rhythm of leptin secretion in male rats ' (2000 ) 224 Proc. Soc. Exp. Biol. Med. : 152 -158.

    • Search Google Scholar
  • Matkovic, V., Ilich, J. Z., Skugor, M., Badenhop, N. E., Goel, P., Clairmont, A., Klisovic, D., Nahhas, R. W., Landoll, J. D. (1997) Leptin is inversely related to age at menarche in human females. J. Clin. Endocrinol. Metab. 82 , 3239–3245.

    Landoll J. D. , 'Leptin is inversely related to age at menarche in human females ' (1997 ) 82 J. Clin. Endocrinol. Metab. : 3239 -3245.

    • Search Google Scholar
  • Meguid, M. M., Fetissov, S. O., Varma, M., Sato, T., Zhang, L., Laviano, A., Rossi-Fanelli, F. F. (2000) Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16 , 843–857.

    Rossi-Fanelli F. F. , 'Hypothalamic dopamine and serotonin in the regulation of food intake ' (2000 ) 16 Nutrition : 843 -857.

    • Search Google Scholar
  • Mercer, J. G., Moar, K. M., Rayner, D. V., Trayhurn, P., Hoggard, N. (1997) Regulation of Leptin receptor and NPY gene expression in hypothalamus of Leptin-treated obese (ob/ob) and cold exposed lean mice. FEBS Letters 402 , 185–188.

    Hoggard N. , 'Regulation of Leptin receptor and NPY gene expression in hypothalamus of Leptin-treated obese (ob/ob) and cold exposed lean mice ' (1997 ) 402 FEBS Letters : 185 -188.

    • Search Google Scholar
  • Mocchegiani, E., Bulian, D., Santarelli, L., Tibaldi, A., Muzzioli, M., Pierpaoli, W., Fabris, N. (1994) The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice. J. Neuroimmunol. 53 , 189–201.

    Fabris N. , 'The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice ' (1994 ) 53 J. Neuroimmunol. : 189 -201.

    • Search Google Scholar
  • Mocchegiani, E., Bulian, D., Santarelli, L., Tibaldi, A., Muzzioli, M., Lesnikov, V., Pierpaoli, W., Fabris, N. (1996). The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice. J. Pharmacol. Exp. Ther. 277 , 1200–1208.

    Fabris N. , 'The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice ' (1996 ) 277 J. Pharmacol. Exp. Ther. : 1200 -1208.

    • Search Google Scholar
  • Mocchegiani, E., Santarelli, L., Tibaldi, A., Muzzioli, M., Bulian, D., Cipriano, K., Olivieri, F., Fabris, N. (1998) Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival. J. Neuroimmunol. 86 , 111–122.

    Fabris N. , 'Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival ' (1998 ) 86 J. Neuroimmunol. : 111 -122.

    • Search Google Scholar
  • Mocchegiani, E., Perisin, L., Santarelli, L., Tibaldi, A., Zorzet, S., Rapozzi, V., Giacconi, R., Bulian, D., Giraldi, T. (1999) Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2. Int. J. Immunopharmacol. 21 , 27–46.

    Giraldi T. , 'Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2 ' (1999 ) 21 Int. J. Immunopharmacol. : 27 -46.

    • Search Google Scholar
  • Mustonen, A. M., Nieminen, P., Hyvarinen, H. (2001) Preliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin levels. Endocrine 16 , 43–46.

    Hyvarinen H. , 'Preliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin levels ' (2001 ) 16 Endocrine : 43 -46.

    • Search Google Scholar
  • Mustonen, A. M., Nieminen, P., Hyvarinen, H., Asikainen, J. (2001) Exogenous melatonin elevates the plasma leptin and thyroxine concentrations of the mink (Mustela vison) . Z. Naturforsch. [C] 55 , 806–813.

    Asikainen J. , 'Exogenous melatonin elevates the plasma leptin and thyroxine concentrations of the mink (Mustela vison) ' (2001 ) 55 Z. Naturforsch. [C] : 806 -813.

    • Search Google Scholar
  • Olusi, S., Al-Awadhi, A., Agabeyaka, C., Abraham, M., George, S. (2003) Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population. Biol. Trace. Elem. Res. 91 , 137–144.

    George S. , 'Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population ' (2003 ) 91 Biol. Trace. Elem. Res. : 137 -144.

    • Search Google Scholar
  • Ott, E. S., Shay, N. F. (2001) Zinc deficiency reduces leptin gene expression and leptin secretion in rat adipocytes. Exp. Biol. Med. (Maywood) 226 , 841–846.

    Shay N. F. , 'Zinc deficiency reduces leptin gene expression and leptin secretion in rat adipocytes ' (2001 ) 226 Exp. Biol. Med. (Maywood) : 841 -846.

    • Search Google Scholar
  • Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Bone, T., Collins, F. (1995) Effects of the obese gene-product on body weight regulation in ob/ob mice. Science 269 , 540–543.

    Collins F. , 'Effects of the obese gene-product on body weight regulation in ob/ob mice ' (1995 ) 269 Science : 540 -543.

    • Search Google Scholar
  • Prasad, A. S. (1985) Clinical manifestations of zinc deficiency. Annu. Rev. Nutr. 5 , 341–363.

    Prasad A. S. , 'Clinical manifestations of zinc deficiency ' (1985 ) 5 Annu. Rev. Nutr. : 341 -363.

    • Search Google Scholar
  • Prunet-Marcassus, B., Desbazeille, M., Bros, A., Louche, K., Delagrange, P., Renard, P., Casteilla, L., Penicaud, L. (2003) Melatonin reduces body weight gain in Sprague-Dawley rats with diet-induced obesity. Endocrinology 144 , 5347–5352.

    Penicaud L. , 'Melatonin reduces body weight gain in Sprague-Dawley rats with diet-induced obesity ' (2003 ) 144 Endocrinology : 5347 -5352.

    • Search Google Scholar
  • Rasmussen, D. D., Boldt, B. M., Wilkinson, C. W., Yellon, S. M., Matsumoto, A. M. (1999) Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology 140 , 1009–1012.

    Matsumoto A. M. , 'Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels ' (1999 ) 140 Endocrinology : 1009 -1012.

    • Search Google Scholar
  • Rasmussen, D. D., Mitton, D. R., Larsen, S. A., Yellon, S. M. (2001) Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses. J. Pineal. Res. 31 , 89–94.

    Yellon S. M. , 'Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses ' (2001 ) 31 J. Pineal. Res. : 89 -94.

    • Search Google Scholar
  • Reiter, R. J. (1993) The melatonin rhythm: both a clock and a calendar. Experientia 49 , 654–664.

    Reiter R. J. , 'The melatonin rhythm: both a clock and a calendar ' (1993 ) 49 Experientia : 654 -664.

    • Search Google Scholar
  • Reiter, R. J., Tan, D., Kim, S. J., Manchester, L. C., Qi, W., Garcia, J. J., Cabrera, J. C., El-Sokkary, G., Rouvier-Garay, V. (1999) Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mech. Ageing Dev. 110 , 157–173.

    Rouvier-Garay V. , 'Augmentation of indices of oxidative damage in life-long melatonin-deficient rats ' (1999 ) 110 Mech. Ageing Dev. : 157 -173.

    • Search Google Scholar
  • Safai-Kutti, S., Kutti, J. (1986) Zinc supplementation in anorexia nervosa. Am. J. Clin. Nutr. 44 , 581–582.

    Kutti J. , 'Zinc supplementation in anorexia nervosa ' (1986 ) 44 Am. J. Clin. Nutr. : 581 -582.

    • Search Google Scholar
  • Selvais, P. L., Labuche, C., Nguyen, X. N., Ketelslegers, J. M., Denef, J. F., Maiter, D. M. (1997) Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat. J. Neuroendocrinol. 9 , 55–62.

    Maiter D. M. , 'Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat ' (1997 ) 9 J. Neuroendocrinol. : 55 -62.

    • Search Google Scholar
  • Sierra-Honigmann, M. R., Nath, A. K., Murakami, C., Garcia-Cardena, G., Papapetropoulos, A., Sessa, W. C., Madge, L. A., Schechner, J. S., Schwabb, M. B., Polverini, P. J., Flores-Riveros, J. R. (1998) Biological action of leptin as an angiogenic factor. Science 281 , 1683–1686.

    Flores-Riveros J. R. , 'Biological action of leptin as an angiogenic factor ' (1998 ) 281 Science : 1683 -1686.

    • Search Google Scholar
  • Skwarlo-Sonta, K. (1996) Functional connections between the pineal gland and immune system. Acta Neurobiol. Exp. (Wars.) 56 , 341–357.

    Skwarlo-Sonta K. , 'Functional connections between the pineal gland and immune system ' (1996 ) 56 Acta Neurobiol. Exp. (Wars.) : 341 -357.

    • Search Google Scholar
  • Tallman, D. L., Taylor, C. G. (2003) Effects of dietary fat and zinc on adiposity, serum leptin and adipose fatty acid composition in C57BL/6J mice. J. Nutr. Biochem. 14 , 17–23.

    Taylor C. G. , 'Effects of dietary fat and zinc on adiposity, serum leptin and adipose fatty acid composition in C57BL/6J mice ' (2003 ) 14 J. Nutr. Biochem. : 17 -23.

    • Search Google Scholar
  • Trayhurn, P., Hoggard, N., Mercer, J. G., Rayner, D. V. (1999) Leptin: fundamentel aspects. Int. J. Obes. Relat. Metab. Disord. 23 , 22–28.

    Rayner D. V. , 'Leptin: fundamentel aspects ' (1999 ) 23 Int. J. Obes. Relat. Metab. Disord. : 22 -28.

    • Search Google Scholar
  • Wada, L., King, J. C. (1986) Effect of low zinc intakes on basal metabolic rate, thyroid hormones and protein utilization in adult men. J. Nutr. 116 , 1045–1053.

    King J. C. , 'Effect of low zinc intakes on basal metabolic rate, thyroid hormones and protein utilization in adult men ' (1986 ) 116 J. Nutr. : 1045 -1053.

    • Search Google Scholar
  • Wilkinson, M., Arendt, J., Bradtke, J., de Ziegler, D. (1997) Determination of a dark-induced increase of pineal N-acetyl transferase activity and simultaneous radioimmunoassay of melatonin in pineal, serum and pituitary tissue of the male rat. J. Endocrinol. 72 , 243–244.

    Ziegler D. , 'Determination of a dark-induced increase of pineal N-acetyl transferase activity and simultaneous radioimmunoassay of melatonin in pineal, serum and pituitary tissue of the male rat ' (1997 ) 72 J. Endocrinol. : 243 -244.

    • Search Google Scholar
  • Wolden-Hanson, T., Mitton, D. R., McCants, R. L., Yellon, S. M., Wilkinson, C. W., Matsumoto, A. M., Rasmussen, D. D. (2000) Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology 141 , 487–497.

    Rasmussen D. D. , 'Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat ' (2000 ) 141 Endocrinology : 487 -497.

    • Search Google Scholar
  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., Friedman, J. M. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372 , 425–432.

    Friedman J. M. , 'Positional cloning of the mouse obese gene and its human homologue ' (1994 ) 372 Nature : 425 -432.

    • Search Google Scholar