1. Wu C, Yang L, Tucker D, Dong Y, Zhu L, Duan R, et al. Beneficial effects of exercise pretreatment in a sporadic Alzheimer’s rat model. Med Sci Sports Exerc 2018; 50:945-956.
2. Lu Y, Dong Y, Tucker D, Wang R, Ahmed ME, Brann D, et al. Treadmill exercise exerts neuroprotection and regulates microglial polarization and oxidative stress in a streptozotocin-induced rat model of sporadic Alzheimer’s disease. J Alzheimers Dis 2017; 56:1469-1484.
3. McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol 2013; 126:479-497.
4. Liao S, Deng H, Huang S, Yang J, Wang S, Yin B, et al. Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett 2015; 25:1541-1545.
5. Alimohammadi-Kamalabadi M, Eshraghian M, Zarindast M-R, Aliaghaei A, Pishva H. Effect of creatine supplementation on cognitive performance and apoptosis in a rat model of amyloid-beta-induced. Iran J Basic Med Sci 2016; 19:1159-1165.
6. Kim J, Yoon H, Basak J, Kim J. Apolipoprotein E in synaptic plasticity and Alzheimer’s disease: potential cellular and molecular mechanisms. Mol Cells 2014; 37:767-776.
7. Nyarko JNK, Quartey MO, Pennington PR, Heistad RM, Dea D, Poirier J, et al. Profiles of β-amyloid peptides and key secretases in brain autopsy samples differ with sex and APOE ε4 status: Impact for risk and progression of alzheimer disease. Neuroscience 2018; 373:20-36.
8. Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A 2009; 106:6820-6825.
9. Huang YA, Zhou B, Wernig M, Südhof TC. ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and Aβ secretion. Cell 2017; 168:427-441.e421.
10. Shen J, Kelleher RJ, 3rd. The presenilin hypothesis of Alzheimer’s disease: Evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A 2007; 104:403-409.
11. Hardy J, Selkoe DJ. The amyloid hypothesis of Aalzheimer’s disease: Progress and problems on the road to therapeutics. Science 2002; 297:353-356.
12. Weihl CC, Ghadge GD, Kennedy SG, Hay N, Miller RJ, Roos RP. Mutant presenilin-1 induces apoptosis and downregulates Akt/PKB. J Neurosci 1999; 19:5360-5369.
13. Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, et al. Increased Amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 1996; 383:710-713.
14. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 1996; 2:864-870.
15. Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, et al. Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 1996; 17:1005-1013.
16. Sudo S, Shiozawa M, Cairns NJ, Wada Y. Aberrant accentuation of neurofibrillary degeneration in the hippocampus of Alzheimer’s disease with amyloid precursor protein 717 and presenilin-1 gene mutations. J Neurol Sci 2005; 234:55-65.
17. Mattson MP, Gary DS, Chan SL, Duan W. Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer’s disease. Biochem Soc Symp 2001:151-162.
18. Revett TJ, Baker GB, Jhamandas J, Kar S. Glutamate system, amyloid ß peptides and tau protein: Functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci 2013; 38:6-23.
19. West MJ, Coleman PD, Flood DG, Troncoso JC. Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 1994; 344:769-772.
20. Findley CA, Bartke A, Hascup KN, Hascup ER. Amyloid beta-related alterations to glutamate signaling dynamics during Alzheimer’s disease progression. ASN Neuro 2019; 11:1759091419855541.
21. Watt G, Karl T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front Pharmacol 2017; 8:20-25.
22. Russo EB. Cannabis therapeutics and the future of neurology. Front Integr Neurosci 2018; 12:51-61.
23. Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R, Iuvone T. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett 2006; 399:91-95.
24. Hamelink C, Hampson A, Wink DA, Eiden LE, Eskay RL. Comparison of cannabidiol, anti-oxidants, and diuretics in reversing binge ethanol-induced neurotoxicity. J Pharmacol Exp Ther 2005; 314:780-788.
25. Mukhopadhyay P, Rajesh M, Horváth B, Bátkai S, Park O, Tanchian G, et al. Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic Biol Med 2011; 50:1368-1381.
26. Esposito G, De Filippis D, Carnuccio R, Izzo AA, Iuvone T. The marijuana component cannabidiol inhibits beta-Amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J Mol Med (Berl) 2006; 84:253-258.
27. Janefjord E, Mååg JL, Harvey BS, Smid SD. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell Mol Neurobiol 2014; 34:31-42.
28. Scuderi C, Steardo L, Esposito G. Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement. Phytother Res 2014; 28:1007-1013.
29. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: A randomized trial. JAMA 2008; 300:1027-1037.
30. Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS, et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2010; 2:32-48.
31. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 2011; 108:3017-3022.
32. Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 2007; 115:3086-3094.
33. Ebrahimnezhad N, Nayebifar S, Soltani Z, Khoramipour K. High-intensity interval training reduced oxidative stress and apoptosis in the hippocampus of male rats with type 2 diabetes: The role of the PGC1α-Keap1-Nrf2 signaling pathway. Iran J Basic Med Sci 2023; 26:1313-1319.
34. Bartlett JD, Close GL, MacLaren DP, Gregson W, Drust B, Morton JP. High-intensity interval running is perceived to be more enjoyable than moderate-intensity continuous exercise: implications for exercise adherence. J Sports Sci 2011; 29:547-553.
35. Freitas DA, Rocha-Vieira E, Soares BA, Nonato LF, Fonseca SR, Martins JB, et al. High intensity interval training modulates hippocampal oxidative stress, BDNF and inflammatory mediators in rats. Physiol Behav 2018; 184:6-11.
36. Vasconcelos-Filho FSL, da Rocha ESRC, Martins JER, Godinho WDN, da Costa VV, Ribeiro JKC, et al. Neuroprotector effect of daily 8-minutes of high-intensity interval training in rat Aβ(1-42) Alzheimer disease model. Curr Alzheimer Res 2020; 17:1320-1333.
37. Li B, Liang F, Ding X, Yan Q, Zhao Y, Zhang X, et al. Interval and continuous exercise overcome memory deficits related to β-amyloid accumulation through modulating mitochondrial dynamics. Behav Brain Res 2019; 376:112171.
38. Council NR. Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, DC: The National Academies Press; 2011.
39. Lorenzo A, Yankner BA. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc Natl Acad Sci U S A 1994; 91:12243-12247.
40. Gholipour P, Komaki A, Ramezani M, Parsa H. Effects of the combination of high-intensity interval training and Ecdysterone on learning and memory abilities, anti-oxidant enzyme activities, and neuronal population in an Amyloid-beta-induced rat model of Alzheimer’s disease. Physiol Behav 2022; 251:113817.
41.Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates: Elsevier Science; 2013.
42. Cheng D, Spiro AS, Jenner AM, Garner B, Karl T. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J Alzheimers Dis 2014; 42:1383-1396.
43. Zgair A, Wong JC, Lee JB, Mistry J, Sivak O, Wasan KM, et al. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines. Am J Transl Res 2016; 8:3448-3459.
44. Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil 2007; 14:753-760.
45. Naderi S, Habibi A, Kesmati M, Rezaie A, Ghanbarzadeh M. The effects of six weeks high intensity interval training on amyloid beta1-42 peptide in hippocampus of rat model of Alzheimer disease induced with STZ. J Clin Res Paramed Sci 2018; 7:e86866.
46. Medhat E, Rashed L, Abdelgwad M, Aboulhoda BE, Khalifa MM, El-Din SS. Exercise enhances the effectiveness of vitamin D therapy in rats with Alzheimer’s disease: Emphasis on oxidative stress and inflammation. Metabolic Brain Disease 2020; 35:111-120.
47. Choi DH, Kwon IS, Koo JH, Jang YC, Kang EB, Byun JE, et al. The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type. J Exerc Nutrition Biochem 2014; 18:225-233.
48. Rodrigues L, Dutra MF, Ilha J, Biasibetti R, Quincozes-Santos A, Leite MC, et al. Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin. J Neural Transm (Vienna) 2010; 117:1295-1305.
49. Hajizade Ghonsulakandi S, Sheikh M, Dehghan Shasaltaneh M, Chopani S, Naghdi N. The association between effective dose of magnesium and mild compulsive exercise on spatial learning, memory, and motor activity of adult male rats. Biol Trace Elem Res 2017; 178:235-245.
50. Kodali M, Megahed T, Mishra V, Shuai B, Hattiangady B, Shetty AK. Voluntary running exercise-mediated enhanced neurogenesis does not obliterate retrograde spatial memory. J Neurosci 2016; 36:8112-8122.
51. Chesworth R, Cheng D, Staub C, Karl T. Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model. Frontiers in Pharmacology 2022; 13 :931384.
52. Amini M, Abdolmaleki Z. The effect of cannabidiol coated by nano-chitosan on learning and memory, hippocampal CB1 and CB2 levels, and amyloid plaques in an Alzheimer’s disease rat model. Neuropsychobiology 2021; 81:171-183.
53. Zhang XB, Li J, Gu J, Zeng YQ. Roles of cannabidiol in the treatment and prevention of Alzheimer’s disease by multi-target actions. Mini Rev Med Chem 2022; 22:43-51.
54. Li B, Liang F, Ding X, Yan Q, Zhao Y, Zhang X, et al. Interval and continuous exercise overcome memory deficits related to β-amyloid accumulation through modulating mitochondrial dynamics. Behavioural brain research 2019; 376:112171.
55. Herbst EA, Holloway GP. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex. Appl Physiol Nutr Metab 2016; 41:799-801.
56. Saedi Marghmaleki V, Alaei HA, Azizi Malekabadi H, Pilehvarian A. Effect of physical activity on symptoms of morphine addiction in rats, after and before of lesion of the mPFC area. Iran J Basic Med Sci 2013; 16:1091-1099.
57. Baek SS, Kim SH. Treadmill exercise ameliorates symptoms of Alzheimer disease through suppressing microglial activation-induced apoptosis in rats. J Exerc Rehabil 2016; 12:526-534.
58. Peng Y, Chi R, Liu G, Tian W, Zhang J, Zhang R. Aerobic exercise regulates apoptosis through the PI3K/Akt/GSK-3β signaling pathway to improve cognitive impairment in alzheimer’s disease mice. Neural Plast 2022; 2022:1500710.
59. da Silva VK, de Freitas BS, da Silva Dornelles A, Nery LR, Falavigna L, Ferreira RDP, et al. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: Implications for neuroprotection. Molecular Neurobiology 2014; 49:222-233.
)