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Acid folic và Coenzym Q10 cải thiện chức năng nhận thức trên chuột được tiêm Streptozotocin vào não thất

2012 Mar-Apr; 15(2): 719–724.

(Chúng tôi xin đăng toàn văn nghiên cứu quốc tế năm 2012 chứng minh tác dụng dự phòng suy giảm trí nhớ của acid folic và Coenzym Q10. Chỉ dịch tóm tắt những ý chính, cốt yếu về ý định và kết quả nghiên cứu)

Tóm tắt:

Nghiên cứu này nhằm nghiên cứu ảnh hưởng của chất chống oxy hóa tan trong chất béo, coenzym Q10 (CoQ10) và axit folic trong việc học và ghi nhớ ở chuột với tiêm streptozotocin vào trong não thất, một mô hình động vật gây chuột bị bệnh Alzheimer. Kết quả cho thấy hiệu năng học tập và trí nhớ bị suy giảm đáng kể ở chuột với ICV-STZ (P <0,001), tuy nhiên CoQ10 và acid folic dùng đơn trị liệu hoặc kết hợp cùng nhau đã ngăn ngừa đáng kể suy giảm nhận thức (P <0,001).

Kết luận: Kết quả hiện tại cho thấy CoQ10 và axit folic có tác dụng điều trị và phòng ngừa suy giảm nhận thức trong bệnh Alzheimer


Folic Acid and Coenzyme Q10 Ameliorate Cognitive Dysfunction in the Rats with Intracerebroventricular Injection of Streptozotocin



The present study aimed to investigate the effects of a fat soluble antioxidant, coenzyme Q10 (CoQ10) and folic acid on learning and memory in the rats with intracerebroventricular injection of streptozotocin (ICV-STZ), an animal model of sporadic type of Alzheimer’s disease.

Materials and Methods

The lesion groups were injected bilaterally with ICV-STZ (1.5 mg/kg b.wt., in normal saline). In the treated groups, rats received folic acid (4 mg/kg; i.p.) or CoQ10 (10 mg/kg; i.p.), either alone or together, for 21 days. Passive avoidance learning test was used for evaluation of learning and memory.


The results showed that learning and memory performance was significantly impaired in the rats with ICV-STZ (P< 0.001), however CoQ10 and folic acid, either alone or together, prevented impairments significantly (P< 0.001), as there was not any significant difference between these treated lesion groups and control group.


The present results suggest that CoQ10 and folic acid have therapeutic and preventive effects on cognitive impairments in Alzheimer’s disease.

Key Words: Alzheimer disease, Coenzyme Q10, Folic acid, Passive avoidance learning, Streptozotocin.

“Hiện nay trên thị trường Việt Nam chỉ có Homo BQ là kết hợp được hai thành phần quan trọng là acid folic và Coenzym Q10, do đó sản phảm có tác dụng đặc biệt tốt cho người bệnh tăng huyết áp, xơ vữa động mạch và dự phòng duy giảm trí nhớ”.

Materials and Methods

Male Wistar rats (300±20 g; 12 months old; provided by the Pasteur Institute of Iran) were housed four per cage and maintained on a 12 hr light–dark cycle in an air conditioned constant temperature (23±1 °C) room, with food and water made available ad libitum. The Ethic Committee for Animal Experiments at Isfahan University approved the study. Animals were divided into five groups (n= 10-11 in each group): the sham, the lesion, the lesion + folic acid, the lesion + Q10 and the lesion + folic acid + Q10.

The rats were anesthetized with chloral hydrates (400 mg/kg, i.p.) and their heads were fixed in a stereotaxic frame. A heating pad was used to maintain body temperature at 36.5±0.5 °C. The skull was exposed and two small holes were drilled and injection canula was lowered into the lateral ventricles (AP=-0.8 mm; ML= ±1.6 mm; DV= -4.2 mm) (30). Injection canula was connected to a Hamilton syringe attached to a micro-injector unit. The lesion groups received a bilateral ICV injection of STZ (1.5 mg/kg, body weight in saline, 4 µl/injection site) as in previous studies (9). The sham groups underwent the same surgical procedures, but same volume of saline was injected instead of STZ.

From the second day after surgery, rats in different treated groups received folic acid (4 mg/kg, in saline; i.p.) or CoQ10 (10 mg/kg in corn oil; i.p.) or both of them for 21 days. Animals in the sham and the lesion groups received same volume of placebo.

After 3 weeks of intracerebroventricular injection of STZ and treatment, the rats were tested with passive avoidance learning (PAL). The apparatus consists of two separate chambers connected through a guillotine door. One chamber was illuminated, while the other was dark. The floor of both chambers consists of steel grids, used to deliver electric shocks. On the acquisition trial, each rat was placed in illuminated chamber while its back was to the guillotine door. After 10 sec of habituation, the guillotine door separating the illuminated and dark chambers was opened. The guillotine door was closed immediately after the rat enters the dark chamber, and an electric foot shock with 1.5 mA intensity was delivered to the floor grids for 3 sec, then the rat was removed from the dark chamber and returned to its home cage. Twenty four hr and one week later, retention latency time to enter the dark chamber was taken in the same way as in the acquisition trial, but foot shock was not delivered, and the latency time was recorded up to a maximum of 300 sec.

Data were analyzed using the SPSS 16 for Windows. The data were analyzed statistically by repeated measures ANOVA followed by Dunnett’s Multiple Comparisons test. The significant level was set at P< 0.05. Results are expressed as mean±SEM.

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The mean initial latency in the acquisition trial was unchanged among the groups. Results from the retention phase of PAL as measured by mean retention latency time have shown twenty four hr after acquisition phase, mean retention latencies in the lesion group (32.66±27.62 sec) was less than the sham (200.63±20.175 sec; P< 0.001), the lesion+folic acid (290.33±31.9 sec; P< 0.001), the lesion+Q10 (292±31.9 sec; P< 0.001.) and the lesion+folic acid+Q10 (288±31.6 sec; P< 0.001) groups ; and one week after acquisition phase, mean retention latencies in the lesion group (20.16±26.82 sec) was less than the sham (205.42±19.58 sec; P< 0.001), the lesion+folic acid (274.5±30.97 sec; P< 0.001), the lesion+Q10 (264.83±30.97 sec; P< 0.001.) and the lesion+folic acid+Q10 (277.16±30.97 sec; P< 0.001) groups . However, the lesion+folic acid, the lesion+Q10 and the lesion+folic acid+Q10 groups comparing to the sham group didn’t have any significant difference.


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Figure 1

Effects of folic acid and coenzyme Q10 on step-through latency in the rats with intracerebroventricular injection of streptozotocin, 24 hr (A) and 1week (B) after PA acquisition. Data are expressed as mean±SEM (n = 10, 11). *** P< 0.001 with respect to the sham group, ††† P< 0.001 with respect to the lesion group.

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The results showed that folic acid and CoQ10, either alone or together prevent learning and memory decline in rats with intracerebroventricular injection of STZ; nevertheless simultaneous application of these two substances did not have better effect than their single application.

Cognitive deficits and biochemical and structural changes in the brain of rats with ICV-STZ mainly were attributed to generating free radicals and altering glucose energy metabolism by depleting ATP synthesis (6, 9, 31).

Studies have demonstrated that the normal cellular energy metabolism is necessary for normal functioning of the brain (28), and when availability of ATP is low in the brain, faulty amyloid precursors protein (APP) metabolism and hyperphosphorylation of the tau-protein are high, that induce production of neuritic placques and neurofibrillary tangles, respectively, which are prominent histopathological markers of AD . It has been demonstrated that intracerebroventricular injection of STZ causes impairment of neural glucose metabolism leading to reduction of ATP and creatine phosphate formation (32, 33), but it was seen that CoQ10 can restore this impaired glucose energy metabolism effectively in ICV-STZ rats (9).

In addition, it is revealed that through improvement of glucose energy metabolism and production of acetyl CoA, and protection of choline acetyltransferase (ChAT) activity, CoQ10 protects cholinergic neurons in the brain of ICV-STZ infused rats that cholinergic neurons are damaged severely (9,34,35).

Oxidative stress plays a pivotal role in Alzheimer’s (36). Oxidative stress damages neuronal membranes lipids and proteins, through generation of free radicals, and therefore damages membrane integrity (37) and reduces the number of nerve cells (38). Because both CoQ10 and folic acid are powerful antioxidant and they have free radical scavenging property, they can reverse the free radical induced damages seen in neurodegenerative diseases and resultant learning and memory defects (23, 39, 40), as seen in our results.

Studies have shown reduction of folic acid as seen in AD results in hyperhomocysteinemia (20, 26, 41, 42). Folic acid deficiency and hyperhomocysteinemia impact neurons by affecting antioxidant defense systems and impairing DNA repair that induces neural cell apoptosis (43, 44). Folic acid supplementation by converting homocysteine into cysteine can increase level of reduced glutathione in all the regions of brain (45). Also, this has beneficial effects in increasing the superoxide dismutase and catalase activities that are protective enzymes against highly reactive free radicals in the brain (46, 47).

Because folic acid and CoQ10 are both reduced in AD patients (26, 27), and folic acid can potentiate endogenous synthesis of CoQ10 (17, 18), therefore, usage of folic acid probably aids to improve AD by increase CoQ10. Hence, administration of folic acid and CoQ10 in AD apparently have same effects, and our results verifies it, because co-administration of CoQ10 and folic acid had same effects on learning and memory as there were in separate administration of them.

Finally, similar to our protocol, other studies have started their intervention, one or two days after ICV-STZ for a period of time (48, 49); and most of them believe that positive effects of their interventions were due to amelioration of ICV-STZ complications, rather than reduction of STZ effectiveness directly; however we do not reject this possibility.

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In conclusion, our findings suggest that CoQ10 and folic acid, either alone or together, protect learning and memory performance in the rats with intracerebroventricular injection of streptozotocin. The data correspond to the possibility that prophylactic treatment with CoQ10 or folic acid can offer protection against Alzheimer’s disease.

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This paper is derived from a MSc thesis. This research was supported by Isfahan University of Medical Sciences, Isfahan, Iran and Isfahan Payame Noor University, Isfahan, Iran.

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1. Flynn BL, Ranno AE. Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives. Ann Pharmacother. 1999;33:188–197. [PubMed]
2. Li X, Yuan HF, Quan QK, Wang JJ, Wang NN, Li M. Scavenging effect of Naoerkang () on amyloid beta-peptide deposition in the hippocampus in a rat model of Alzheimer’s disease. Chin J Integr Med . 2011;17(11):847–53. [PubMed]
3. Herring A, Ambrée O, Tomm M, Habermann H, Sachser N, Paulus W, et al. Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like pathology. Exp Neurol . 2009;216:184–192. [PubMed]
4. Robert R, Dolezal O, Waddington L, Hattarki MK, Cappai R, Masters CL, et al. Engineered antibody intervention strategies for Alzheimer’s disease and related dementias by targeting amyloid and toxic oligomers. Protein Eng Des Sel . 2009;22:199–208. [PubMed]
5. Holscher C, Gengler S, Gault VA, Harriott P, Mallot HA. Soluble beta-amyloid [25-35] reversibly impairs hippocampal synaptic plasticity and spatial learning. Eur J Pharmacol. 2007;561:85–90. [PubMed]
6. Sharma M, Gupta YK. Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci . 2001;68:1021–1029. [PubMed]
7. Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR. Protein oxidation in the brain in Alzheimer’s disease. Neuroscience. 2001;103:373–383. [PubMed]
8. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995;41:1819–1828. [PubMed]
9. Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, et al. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res. 2006;171:9–16. [PubMed]
10. Ishrat T, Parveen K, Khan MM, Khuwaja G, Khan MB, Yousuf S, et al. Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type. Brain Res. 2009;1281:117–127. [PubMed]
11. Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995;1271:195–204. [PubMed]
12. Tsuneki H, Sekizaki N, Suzuki T, Kobayashi S, Wada T, Okamoto T, et al. Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells. Eur J Pharmacol . 2007;566:1–10. [PubMed]
13. McDonald SR, Sohal RS, Forster MJ. Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice. Free Radic Biol Med . 2005;38:729–736. [PubMed]
14. Lass A, Sohal RS. Electron transport-linked ubiquinone-dependent recycling of alpha-tocopherol inhibits autooxidation of mitochondrial membranes. Arch Biochem Biophys. 1998;352:229–236.[PubMed]
15. Dumont M, Kipiani K, Yu F, Wille E, Katz M, Calingasan NY, et al. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2011;27:211–223. [PMC free article] [PubMed]
16. Vranesić-Bender D. The role of nutraceuticals in anti-aging medicine. Acta Clin Croat . 2010;49:537–544. [PubMed]
17. Shinde S, Patil N, Tendolkar A. Coenzyme Q10: A review of essential functions. Internet J Nutr Wellness . 2005;1(2) ISSN: 1937-8297.
18. Folkers K. Relevance of the biosynthesis of coenzyme Q10 and the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun. 1996;224:358–61.[PubMed]
19. Kamen B. Folate and antifolate pharmacology. Semin Oncol. 1997;24:S18–30. [PubMed]
20. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346:476–483. [PubMed]
21. Weinstein SJ, Hartman TJ, Stolzenberg-Solomon R, Pietinen P, Barrett MJ, Taylor PR, et al. Null association between prostate cancer and serum folate, vitamin B(6), vitamin B(12), and homocysteine.Cancer Epidemiol Biomarkers Prev . 2003;12:1271–1272. [PubMed]
22. Reynolds EH. Mental effects of anticonvulsants, and folic acid metabolism. Brain. 1968;91:197–214.[PubMed]
23. Joshi R, Adhikari S, Patro BS, Chattopadhyay S, Mukherjee T. Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. Free Radic Biol Med . 2001;30:1390–1399. [PubMed]
24. Singh R, Kanwar SS, Sood PK, Nehru B. Beneficial effects of folic acid on enhancement of memory and antioxidant status in aged rat brain. Cell Mol Neurobiol . 2011;31:83–91. [PubMed]
25. Bottiglieri T, Reynolds EH, Laundy M. Folate in CSF and age. J Neurol Neurosurg Psychiatry . 2000;69:562. [PMC free article] [PubMed]
26. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55:1449–1455. [PubMed]
27. Isobe C, Abe T, Terayama Y. Increase in the oxidized/total coenzyme Q-10 ratio in the cerebrospinal fluid of Alzheimer’s disease patients. Dement Geriatr Cogn Disord . 2009;28:449–454. [PubMed]
28. Lannert H, Hoyer S. Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci. 1998;112:1199–1208. [PubMed]
29. Ponce-Lopez T, Liy-Salmeron G, Hong E, Meneses A. Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Res . 2011;1426:73–85.[PubMed]
30. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 5th ed. San Diego: Elsevier Academic Press; 2005.
31. Shoham S, Bejar C, Kovalev E, Schorer-Apelbaum D, Weinstock M. Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats. Neuropharmacology . 2007;52:836–843. [PubMed]
32. Duelli R, Schröck H, Kuschinsky W, Hoyer S. Intracerebroventricular injection of streptozotocin induces discrete local changes in cerebral glucose utilization in rats. Int J Dev Neurosci. 1994;12:737–743.[PubMed]
33. Nitsch R, Hoyer S. Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neurosci Lett . 1991;128:199–202. [PubMed]
34. Blokland A, Jolles J. Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin. Pharmacol Biochem Behav. 1993;44:491–494. [PubMed]
35. Hoyer S, Lannert H. Inhibition of the neuronal insulin receptor causes Alzheimer-like disturbances in oxidative/energy brain metabolism and in behavior in adult rats. Ann N Y Acad Sci. 1999;893:301–303.[PubMed]
36. Markesbery WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med. 1997;23:134–147. [PubMed]
37. Liu R, Liu IY, Bi X, Thompson RF, Doctrow SR, Malfroy B, et al. Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc Natl Acad Sci USA. 2003;100:8526–8531. [PMC free article] [PubMed]
38. Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science. 1997;278:412–419.[PubMed]
39. Beal MF. Therapeutic effects of coenzyme Q10 in neurodegenerative diseases. Methods Enzymol . 2004;382:473–487. [PubMed]
40. Rauscher FM, Sanders RA, Watkins JB. Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats. J Biochem Mol Toxicol. 2001;15:41–46. [PubMed]
41. Durand P, Fortin LJ, Lussier-Cacan S, Davignon J, Blache D. Hyperhomocysteinemia induced by folic acid deficiency and methionine load–applications of a modified HPLC method. Clin Chim Acta. 1996;252:83–93. [PubMed]
42. Mattson MP, Kruman II, Duan W. Folic acid and homocysteine in age-related disease. Ageing Res Rev. 2002;1:95–111. [PubMed]
43. Blundell G, Jones BG, Rose FA, Tudball N. Homocysteine mediated endothelial cell toxicity and its amelioration. Atherosclerosis. 1996;122:163–172. [PubMed]
44. Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci. 2000;20:6920–6926. [PubMed]
45. Singh R, Kanwar SS, Sood PK, Nehru B. Beneficial effects of folic Acid on enhancement of memory and antioxidant status in aged rat brain. Cell Mol Neurobiol. 2011;31:83–91. [PubMed]
46. Barber DA, Harris SR. Oxygen free radicals and antioxidants: a review. Am Pharm. 1994;NS34:6–35.[PubMed]
47. Fridovich I. Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol. 1983;23:239–257. [PubMed]
48. Chen S, Liu AR, An FM, Yao WB, Gao XD. Amelioration of neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer’s disease by exendin-4. Age (Dordr) . 2011 [PMC free article][PubMed]
49. Agrawal R, Tyagi E, Shukla R, Nath C. Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol . 2011;21:261–273. [PubMed]

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