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Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models

Year 2022, Volume: 69 Issue: 2, 171 - 181, 25.03.2022
https://doi.org/10.33988/auvfd.847817

Abstract

In this study, it was aimed to investigate the effects of EVOO, rosmarinic acid and donepezil in Alzheimer's model to be created with AlCl3 in rats. For this reason, administration of 100 mg/kg aluminum chloride (AlC3) for 15 days to Sprague Dawley adult male rats; donepezil, Extra-virgin olive oil (EVOO) and rosmarinic acid were administered to three different groups for 21 days by applying treatment protocols. With this study, we were able to demonstrate that cognitive impairment has been occurred after 15 days of AlCl3 administration by oral gavage and treatment protocols prevented the occurrence of AD pathology histopathologically. We also showed that oxidative damage findings which are positively Congo-red stained cell cytoplasm and impaired cell integrity have been observed in serum and hippocampus. Besides, treatment groups showed better cognitive and motor performance, and there was no damage to the cells in control and treatment groups. In the rotarod motor performance test, a significant increase was observed in the donepezil group compared to the AlCl3 group at speeds of 26 and 30 rpm. In MVM, on the 5th day of the experiment, a significant increase was observed in the donepezil group compared to the AlCl3 group, as they were spending more time in the hidden platform area. These results show that 15 days of aluminum exposure is effective in creating a moderate Alzheimer’s pathology, but further chronic research is necessary to explain the efficiencies of rosmarinic acid and EVOO in treatment.

Thanks

This study is produced from the first author’s PhD thesis.

References

  • Abbas T, Faivre E, Hölscher C (2009): Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer’s disease. Behav Brain Res, 205, 265-271.
  • Bazrgar M, Goudarzi I, Lashkarbolouki T, et al (2015): Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat pups. Physiol Behav, 151, 178-188.
  • Bhat AH, Dar KB, Anees S, et al (2015): Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother, 74, 101-110.
  • Birks J (2006): Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev, 25, CD005593.
  • Biswas J, Gupta S, Verma DK, et al (2018): Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer's like pathology. Cell Signal, 42, 211-226.
  • Camicioli R, Bouchard T, Licis L (2006): Dual-tasks and walking fast: relationship to extra-pyramidal signs in advanced Alzheimer disease. J Neurol Sci, 248, 205-209.
  • Casarrubea M, Sorbera F, Crescimanno G (2009): Multivariate data handling in the study of rat behavior: an integrated approach. Behav Res Methods, 41, 772-781.
  • Chiroma SM, Baharuldin MTH, Taib M, et al (2019): Protective effects of centella asiatica on cognitive deficits induced by D-gal/AlCl3 via inhibition of oxidative stress and attenuation of acetylcholinesterase level. Toxics, 7, 19.
  • Cotman CW, Head E (2008): The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approaches. J Alzheimers Dis, 4, 685-707.
  • Davis K, Burnett K, Gigg J (2017): Water and T-maze protocols are equally efficient methods to assess spatial memory in 3xTg Alzheimer’s disease mice. Behav Brain Res, 331, 54-66.
  • Doody RS, Geldmacher DS, Gordon B, et al (2001): Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Archives of Neurology, 58, 427-33.
  • Enas AK (2010): Study of the possible protective and therapeutic influence of Coriander (Coriandrum sativum L.) against neurodegenerative disorders and Alzheimer’s disease induced by aluminum chloride in cerebral cortex of male Albino rats. Nat Sci, 8, 202-213.
  • Frisoni GB, Boccardi M, Barkhof F, et al (2017): Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol, 16, 661-676.
  • Genovese A, Caporas ON, Villani V, et al (2015): Olive oil phenolic compounds affect the release of aroma compounds. Food Chem, 181, 284-294.
  • Handley SL, Mithani S (1984): Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour. Naunyn Schmiedebergs Arch Pharmacol, 327, 1-5.
  • Hara C, Manabe K, Ogawa N (1981): Influence of activity-stress on thymus, spleen and adrenal weights of rats: Possibility for an immunodeficiency model. Physiology & Behavior, 27, 243-8.
  • Hegerl U, Mergl R, Henkel V, et al (2003): Kinematic analysis of the effects of donepezil hydrochloride on hand motor function in patients with Alzheimer dementia. J Clin Psychopharmacol, 23, 214-216.
  • Howes LG (2014): Cardiovascular effects of drugs used to treat Alzheimer’s disease. Drug Saf, 37, 391-395.
  • Huang WJ, Zhang X, Chen WW (2016): Role of oxidative stress in Alzheimer’s disease. Biomed Rep, 4, 519-522.
  • Iuvone T, De Filippis D, Esposito G, et al (2006): The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-β peptide-induced neurotoxicity. J Pharmacol Exp, 17, 1143-1149.
  • Kapadia M, XU J, Sakic B (2016): The water maze paradigm in experimental studies of chronic cognitive disorders: Theory, protocols, analysis, and inference. Neurosci Biobehav Rev, 68, 195-217.
  • Lakshmi B, Sudhakar M, Prakash KS (2015): Protective effect of selenium against aluminum chloride-induced Alzheimer’s disease: behavioral and biochemical alterations in rats. Biol Trace Elem Res, 165, 67-74.
  • Livesey A, Garty F, Shipman A, et al (2019): Lactate dehydrogenase in dermatology practice. Clin Exp Dermatol, 28, 26-33.
  • Mathiyazahan DB, Thenmozhi AJ, Manivasagam T (2015): Protective effect of black tea extract against aluminium chloride-induced Alzheimer's disease in rats, A behavioural, biochemical and molecular approach. J Funct Foods, 16, 423-435.
  • Montedoro G, Servili M, Baldioli M, et al (1992): Simple and hydrolyzable phenolic compounds in virgin olive oil, Their extraction, separation, and quantitative and semiquantitative evaluation by HPLC. J Agric Food Chem, 40, 1571-1576.
  • Mushtaq N, Schmatz R, Pereira LB, et al (2014): Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin induced diabetic rats. Cell Biochem, 32, 287-293.
  • Nakbi A, Tayeb W, Grissa A, et al (2010): Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2, 4-Dichlorophenoxyacetic acid-treated rats. Nutr Metab, 7, 80.
  • Newington JT, Rappon T, Albers S, et al (2012): Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid β and other toxins by decreasing mitochondrial respiration and reactive oxygen species production. J Biol Chem, 44, 37245-37258.
  • Olajide OJ, Yawson EO, Gbadamosi IT, et al (2017): Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer’s disease. Environ Toxicol Pharmacol, 50, 200-211.
  • Ono K, Li L, Takamura Y, et al (2012): Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding. J Biol Chem, 287, 14631-14643.
  • Papandreou MA, Dimakopoulou A, Linardaki ZI, et al (2009): Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behav Brain Res, 198, 352-358.
  • Persson T, Popescu BO, Cedazo-Minguez A (2014): Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid Med Cel Longev, Article ID 427318.
  • Pettersson AF, Engardt M, Wahlund LO (2002): Activity level and balance in subjects with mild Alzheimer’s disease. Dement Geriatr Cogn, 13, 213-216.
  • Prut L, Belzung C (2003): The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol, 463, 3-33.
  • Santos F, Rao V (2000): Antiinflammatory and antinociceptive effects of 1, 8 cineole a terpenoid oxide present in many plant essential oils. Phytother Res, 14, 240-244.
  • Shamasundar N, Rao TS, Naidu MD, et al (2006) A new insight on Al-maltolate-treated aged rabbit as Alzheimer’s animal model. Brain Res Rev, 52, 275-292.
  • Sperling RA, Aisen PS, Beckett LA, et al (2011): Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7, 280-292.
  • Tian H, Ding N, Guo M, et al (2019): Analysis of Learning and Memory Ability in an Alzheimer’s Disease Mouse Model using the Morris Water Maze. JoVE, 152, e60055.
  • Uysal N, Baykara B, Kiray M, et al (2013): Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats. Turk Neurosurg, 23, 129-137.
  • Valvona CJ, Fillmore HL, Nunn PB, et al (2016): The regulation and function of lactate dehydrogenase a: therapeutic potential in brain tumor. Brain Pathol, 1, 3-17.
  • Vinters HV (2015): Emerging concepts in Alzheimer’s disease. Annu Rev Pathol, 10, 291-319.
  • Vlassenko AG, Vaishnavi SN, Couture L, et al (2010): Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition. Proc Natl Acad Sci, 41, 17763-17767.
  • Winblad B, Engedal K, Soininen H, et al (2001): A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology, 57, 489-495.
  • Wu M-Y, Esteban G, Brogi S, et al (2016): Donepezil-like multifunctional agents: design, synthesis, molecular modeling and biological evaluation. Eur J Med Chem, 121, 864-79.
  • Zidan M, Arcoverde C, Araújo NB, et al (2012): Alterações motoras e funcionais em diferentes estágios da doença de Alzheimer. Arch Clin, 39, 161-165.
Year 2022, Volume: 69 Issue: 2, 171 - 181, 25.03.2022
https://doi.org/10.33988/auvfd.847817

Abstract

References

  • Abbas T, Faivre E, Hölscher C (2009): Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer’s disease. Behav Brain Res, 205, 265-271.
  • Bazrgar M, Goudarzi I, Lashkarbolouki T, et al (2015): Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat pups. Physiol Behav, 151, 178-188.
  • Bhat AH, Dar KB, Anees S, et al (2015): Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother, 74, 101-110.
  • Birks J (2006): Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev, 25, CD005593.
  • Biswas J, Gupta S, Verma DK, et al (2018): Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer's like pathology. Cell Signal, 42, 211-226.
  • Camicioli R, Bouchard T, Licis L (2006): Dual-tasks and walking fast: relationship to extra-pyramidal signs in advanced Alzheimer disease. J Neurol Sci, 248, 205-209.
  • Casarrubea M, Sorbera F, Crescimanno G (2009): Multivariate data handling in the study of rat behavior: an integrated approach. Behav Res Methods, 41, 772-781.
  • Chiroma SM, Baharuldin MTH, Taib M, et al (2019): Protective effects of centella asiatica on cognitive deficits induced by D-gal/AlCl3 via inhibition of oxidative stress and attenuation of acetylcholinesterase level. Toxics, 7, 19.
  • Cotman CW, Head E (2008): The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approaches. J Alzheimers Dis, 4, 685-707.
  • Davis K, Burnett K, Gigg J (2017): Water and T-maze protocols are equally efficient methods to assess spatial memory in 3xTg Alzheimer’s disease mice. Behav Brain Res, 331, 54-66.
  • Doody RS, Geldmacher DS, Gordon B, et al (2001): Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Archives of Neurology, 58, 427-33.
  • Enas AK (2010): Study of the possible protective and therapeutic influence of Coriander (Coriandrum sativum L.) against neurodegenerative disorders and Alzheimer’s disease induced by aluminum chloride in cerebral cortex of male Albino rats. Nat Sci, 8, 202-213.
  • Frisoni GB, Boccardi M, Barkhof F, et al (2017): Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol, 16, 661-676.
  • Genovese A, Caporas ON, Villani V, et al (2015): Olive oil phenolic compounds affect the release of aroma compounds. Food Chem, 181, 284-294.
  • Handley SL, Mithani S (1984): Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour. Naunyn Schmiedebergs Arch Pharmacol, 327, 1-5.
  • Hara C, Manabe K, Ogawa N (1981): Influence of activity-stress on thymus, spleen and adrenal weights of rats: Possibility for an immunodeficiency model. Physiology & Behavior, 27, 243-8.
  • Hegerl U, Mergl R, Henkel V, et al (2003): Kinematic analysis of the effects of donepezil hydrochloride on hand motor function in patients with Alzheimer dementia. J Clin Psychopharmacol, 23, 214-216.
  • Howes LG (2014): Cardiovascular effects of drugs used to treat Alzheimer’s disease. Drug Saf, 37, 391-395.
  • Huang WJ, Zhang X, Chen WW (2016): Role of oxidative stress in Alzheimer’s disease. Biomed Rep, 4, 519-522.
  • Iuvone T, De Filippis D, Esposito G, et al (2006): The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-β peptide-induced neurotoxicity. J Pharmacol Exp, 17, 1143-1149.
  • Kapadia M, XU J, Sakic B (2016): The water maze paradigm in experimental studies of chronic cognitive disorders: Theory, protocols, analysis, and inference. Neurosci Biobehav Rev, 68, 195-217.
  • Lakshmi B, Sudhakar M, Prakash KS (2015): Protective effect of selenium against aluminum chloride-induced Alzheimer’s disease: behavioral and biochemical alterations in rats. Biol Trace Elem Res, 165, 67-74.
  • Livesey A, Garty F, Shipman A, et al (2019): Lactate dehydrogenase in dermatology practice. Clin Exp Dermatol, 28, 26-33.
  • Mathiyazahan DB, Thenmozhi AJ, Manivasagam T (2015): Protective effect of black tea extract against aluminium chloride-induced Alzheimer's disease in rats, A behavioural, biochemical and molecular approach. J Funct Foods, 16, 423-435.
  • Montedoro G, Servili M, Baldioli M, et al (1992): Simple and hydrolyzable phenolic compounds in virgin olive oil, Their extraction, separation, and quantitative and semiquantitative evaluation by HPLC. J Agric Food Chem, 40, 1571-1576.
  • Mushtaq N, Schmatz R, Pereira LB, et al (2014): Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin induced diabetic rats. Cell Biochem, 32, 287-293.
  • Nakbi A, Tayeb W, Grissa A, et al (2010): Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2, 4-Dichlorophenoxyacetic acid-treated rats. Nutr Metab, 7, 80.
  • Newington JT, Rappon T, Albers S, et al (2012): Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid β and other toxins by decreasing mitochondrial respiration and reactive oxygen species production. J Biol Chem, 44, 37245-37258.
  • Olajide OJ, Yawson EO, Gbadamosi IT, et al (2017): Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer’s disease. Environ Toxicol Pharmacol, 50, 200-211.
  • Ono K, Li L, Takamura Y, et al (2012): Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding. J Biol Chem, 287, 14631-14643.
  • Papandreou MA, Dimakopoulou A, Linardaki ZI, et al (2009): Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behav Brain Res, 198, 352-358.
  • Persson T, Popescu BO, Cedazo-Minguez A (2014): Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid Med Cel Longev, Article ID 427318.
  • Pettersson AF, Engardt M, Wahlund LO (2002): Activity level and balance in subjects with mild Alzheimer’s disease. Dement Geriatr Cogn, 13, 213-216.
  • Prut L, Belzung C (2003): The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol, 463, 3-33.
  • Santos F, Rao V (2000): Antiinflammatory and antinociceptive effects of 1, 8 cineole a terpenoid oxide present in many plant essential oils. Phytother Res, 14, 240-244.
  • Shamasundar N, Rao TS, Naidu MD, et al (2006) A new insight on Al-maltolate-treated aged rabbit as Alzheimer’s animal model. Brain Res Rev, 52, 275-292.
  • Sperling RA, Aisen PS, Beckett LA, et al (2011): Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7, 280-292.
  • Tian H, Ding N, Guo M, et al (2019): Analysis of Learning and Memory Ability in an Alzheimer’s Disease Mouse Model using the Morris Water Maze. JoVE, 152, e60055.
  • Uysal N, Baykara B, Kiray M, et al (2013): Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats. Turk Neurosurg, 23, 129-137.
  • Valvona CJ, Fillmore HL, Nunn PB, et al (2016): The regulation and function of lactate dehydrogenase a: therapeutic potential in brain tumor. Brain Pathol, 1, 3-17.
  • Vinters HV (2015): Emerging concepts in Alzheimer’s disease. Annu Rev Pathol, 10, 291-319.
  • Vlassenko AG, Vaishnavi SN, Couture L, et al (2010): Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition. Proc Natl Acad Sci, 41, 17763-17767.
  • Winblad B, Engedal K, Soininen H, et al (2001): A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology, 57, 489-495.
  • Wu M-Y, Esteban G, Brogi S, et al (2016): Donepezil-like multifunctional agents: design, synthesis, molecular modeling and biological evaluation. Eur J Med Chem, 121, 864-79.
  • Zidan M, Arcoverde C, Araújo NB, et al (2012): Alterações motoras e funcionais em diferentes estágios da doença de Alzheimer. Arch Clin, 39, 161-165.
There are 45 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Journal Section Research Article
Authors

Sevim Kandiş 0000-0001-8992-7985

Levent Altıntaş 0000-0002-5148-723X

Servet Kızıldağ 0000-0003-3565-279X

Fatma Simsek 0000-0002-7131-7035

Mehmet Ateş 0000-0002-2764-6579

Hasan Alaçam 0000-0003-3807-2926

Nazan Uysal 0000-0002-2348-7427

Publication Date March 25, 2022
Published in Issue Year 2022Volume: 69 Issue: 2

Cite

APA Kandiş, S., Altıntaş, L., Kızıldağ, S., Simsek, F., et al. (2022). Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 69(2), 171-181. https://doi.org/10.33988/auvfd.847817
AMA Kandiş S, Altıntaş L, Kızıldağ S, Simsek F, Ateş M, Alaçam H, Uysal N. Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models. Ankara Univ Vet Fak Derg. March 2022;69(2):171-181. doi:10.33988/auvfd.847817
Chicago Kandiş, Sevim, Levent Altıntaş, Servet Kızıldağ, Fatma Simsek, Mehmet Ateş, Hasan Alaçam, and Nazan Uysal. “Comparison Anti-Oxidant and Neuroprotective Effects of Extra-Virgin Olive Oil, Donepezil and Rosmarinic Acid on Aluminum Chloride-Induced Alzheimer’s in Rat Models”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 69, no. 2 (March 2022): 171-81. https://doi.org/10.33988/auvfd.847817.
EndNote Kandiş S, Altıntaş L, Kızıldağ S, Simsek F, Ateş M, Alaçam H, Uysal N (March 1, 2022) Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models. Ankara Üniversitesi Veteriner Fakültesi Dergisi 69 2 171–181.
IEEE S. Kandiş, “Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models”, Ankara Univ Vet Fak Derg, vol. 69, no. 2, pp. 171–181, 2022, doi: 10.33988/auvfd.847817.
ISNAD Kandiş, Sevim et al. “Comparison Anti-Oxidant and Neuroprotective Effects of Extra-Virgin Olive Oil, Donepezil and Rosmarinic Acid on Aluminum Chloride-Induced Alzheimer’s in Rat Models”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 69/2 (March 2022), 171-181. https://doi.org/10.33988/auvfd.847817.
JAMA Kandiş S, Altıntaş L, Kızıldağ S, Simsek F, Ateş M, Alaçam H, Uysal N. Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models. Ankara Univ Vet Fak Derg. 2022;69:171–181.
MLA Kandiş, Sevim et al. “Comparison Anti-Oxidant and Neuroprotective Effects of Extra-Virgin Olive Oil, Donepezil and Rosmarinic Acid on Aluminum Chloride-Induced Alzheimer’s in Rat Models”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, vol. 69, no. 2, 2022, pp. 171-8, doi:10.33988/auvfd.847817.
Vancouver Kandiş S, Altıntaş L, Kızıldağ S, Simsek F, Ateş M, Alaçam H, Uysal N. Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer’s in rat models. Ankara Univ Vet Fak Derg. 2022;69(2):171-8.