اثر مواجه مکرر فرمالدئید بر یادگیری، حافظه فضایی و رفتارهای شبه اضطرابی و وسواس در مدل حیوانی موش صحرایی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانش آموخته دانشکده دامپزشکی دانشگاه سمنان، سمنان، ایران

2 گروه علوم پایه، دانشکده دامپزشکی، دانشگاه سمنان

3 گروه علوم پایه دانشکده دامپزشکی، دانشگاه سمنان ،سمنان ، ایران

4 گروه علوم دامی، تغذیه دام و طیور، دانشکده دامپزشکی دانشگاه سمنان، سمنان، ایران

چکیده

فرمالدهید یک ماده­ی آلی فرار است که در صنعت و پزشکی کاربرد فراوان دارد. طبق برخی مطالعات، فرمالدهید توان ورود به مغز را داشته و می­تواند منجر به عوارض عصبی و اختلالات مربوط به حافظه و یادگیری شود. بعضی مطالعات نیز نشان داده اند که فرمالدهید در پروسه­ بیماری آلزایمر نقش دارد. هدف از این مطالعه بررسی اثر فرمالدهید بر حافظه­ی ­فضایی، میزان اضطراب و وسواس در موش صحرایی بود. بدین منظور 24 سر رت بالغ نژاد ویستار به چهار گروه شامل: 1-گروه کنترل، 2-گروه دریافت کننده­ی فرمالدهید به­مقدار ppm1، 3- گروه دریافت کننده­ی فرمالدهید به­مقدار ppm2، و 4-گروه دریافت کننده­ی فرمالدهید به­مقدار ppm3 تقسیم شدند. گروه­های تحت درمان هفت روز متوالی و روزانه شش ساعت مورد مواجهه با فرمالدهید قرار گرفتند. پس از اتمام دوره­ی مواجهه و دوره­های آموزش و تمرین، تست­های ­رفتاری Open Field و ماز آبی موریس انجام شده و داده­ها ثبت و آنالیز شد.. در آزمون ماز آبی موریس، با افزایش دوز فرمالدهید، زمان رسیدن به محل سکوی پنهان و میزان حضور در ربع مخالف سکو افزایش، و مدت زمان حضور در بخش SE  و تعداد دفعات ورود به آن کاهش یافت. در آزمون Open Field، مواجهه با فرمالدهید موجب افزایش معنی­دار تعداد عبور از خطوط و رفتار نظافت و کاهش حرکت بلند شدن روی پاهای عقبی شد (P<0/05). با توجه به یافته­های مطالعه­ی حاضر، مواجهه با فرمالدهید استنشاقی می­تواند بر حافظه و یادگیری اثر مخرب داشته­ و  موجب افزایش اضطراب و وسواس شود.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of repeated exposure to formaldehyde on learning, spatial memory and anxiety-like and obsessive behaviors in the rat animal model

نویسندگان [English]

  • Ava Resae 1
  • saeideh Naeimi 2
  • Mohammad Hassan Yousefi 3
  • Ali Mahdavi 4
1 Semnan University, Semnan, Iran.
2 Department of Basic Sciences, Faculty of Veterinary Medicine, Semnan University, Semnan, Iran
3 Department of basic sciences , Faculty of veterinary Medicine , Semnan University , Semnan- iran .
4 Department of Animal nutrition, rearing and breeding, Faculty of Veterinary Medicine, Semnan University, Semnan, Iran
چکیده [English]

Formaldehyde is a volatile organic substance that is widely used in industry and medicine. According to some studies, formaldehyde has the ability to enter the brain and can lead to neurological complications and disorders related to memory and learning. Some studies have also shown that formaldehyde plays a role in the process of Alzheimer's disease. The aim of this study was to investigate the effect of formaldehyde on spatial memory, anxiety and obsession in rats. For this purpose, 24 adult Wistar rats were divided into four groups including: 1- control group, 2- group receiving formaldehyde in the amount of 1 ppm, 3-group receiving formaldehyde in the amount of 2 ppm, and 4- group receiving formaldehyde in the amount of 3 ppm. The treated groups were exposed to formaldehyde for seven consecutive days and six hours a day. After the completion of the exposure period and the training and training courses, Open Field and Morris water maze behavioral tests were performed and the data were recorded and analyzed. In the Morris water maze test, with increasing formaldehyde dosage, the time to reach the hidden platform and the amount of presence in the opposite quadrant of the platform increased, and the duration of presence in the SE section and the number of times to enter it decreased. In the Open Field test, exposure to formaldehyde caused a significant increase in the number of crossing lines and grooming behavior and a decrease in the lifting movement on the hind legs (P<0.05). According to the findings of the present study, exposure to inhaled formaldehyde can have a destructive effect on memory and learning and can increase anxiety and obsession.

کلیدواژه‌ها [English]

  • Formaldehyde
  • memory
  • learning
  • anxiety
  • rat
Angrini, M., Leslie, J.C., Shephard, R.A. (1998). Effects of Propranolol, Buspirone, pCPA, Reserpine, and Chlordiazepoxide on Open-Field Behavior. Pharmacology Biochemistry and Behavior, 59(2), 387–397.
Aslan, H., Songur, A., Tunc, A.T., Ozen, O.A., Bas, O., Yagmurca, M., Turgut, M., Sarsilmaz, M., Kaplan, S. (2006) Effects of formaldehyde exposure on granule cell number and volume of dentate gyrus: a histopathological and stereological study. Brain Res 1122, 191–200.
Barros, H. M., Tannhauser, S. L., Tannhauser, A. L., Tannhauser,M. (1994) The effects of GABAergic drugs on grooming behavior in theopen field. Pharmacol. Toxicol. 74:339–344.
Dunn, A. J.,Guild, A. L.,Kramarcy, N. R., Ware, M.D.(1981) Benzodiazepinesdecrease grooming in response to novelty but not ACTH or beta-endorphin. Pharmacol. Biochem. Behav. 15:605–608.
Kilburn KH, Seidman BC, Warshaw R (1985) Neurobehavioral and respiratory symptoms of formaldehyde and xylene exposure in histology technicians. Arch Environ Health, 40, 229–233
KIM, K. H., S. A. JAHAN, J. T. LEE (2011): Exposure to formaldehyde and its potential human health hazards. J. Environ. Sci. Health C. 29(4), 277–299.                                                                                                                   
Li Y, Song Z, Ding Y, Xin Y, Wu T, Su T, He R, Tai F, Lian Z (2016) Effects of formaldehyde exposure on anxiety-like and depression-like behavior, cognition, central levels of glucocorticoid receptor and tyrosine hydroxylase in mice. Chemosphere, 144, 2004–2012.
Liu Y, Ye Z, Yang H, et al. (2010). Disturbances of soluble N-ethylmaleimide-sensitive factor attachment proteins in hippocampal synaptosomes contribute to cognitive impairment after repetitive formaldehyde inhalation in male rats. Neuroscience, 169, 1248–1254.
Lu, Z., Li, C.M., Qiao, Y., Yan, Y., Yang, X. (2008) Effect of inhaled formaldehyde on learning and memory of mice. Indoor Air, 18, 77–83.
Malek, F.A., Moritz, K.U., Fanghanel, J. (2003). Formaldehyde inhalation & open field behaviour in rats. Indian J Med Res, 118, 90–96.
Malek, F.A., Moritz, K.U., Fanghanel, J. (2004). Effects of a single inhalative exposure to formaldehydeon the open field behavior of mice. Int J Hyg Environ Health, 207, 151–158.
Makowski, E.C., Ordonez, L.A. (1981). Behavioral alterations induced by formaldehyde-derived tetrahydroisoquinolines. Pharmacol Biochem Behav, 14, 639–643.
Moody, T. W., Merali, Z., Crawley, J. N. (1993). The effects of anxiolyticsand other agents on rat grooming behavior. Ann. NY Acad.Sci. 90:281–290.
Nogueira, M. I., C. BARBIERI, R. VIEIRA, E. R. MARQUES, J. E. MORENO (1997): A practical device for histological fixative procedures that limits formaldehyde deleterious effects in laboratory environments. J. Neurosci. Methods 72(1), 65–70.   
Olivier, J.D.A, Valles, A., Van Heesh, F., Afrasiab-Middleman, A., Roelofs, J.J.P.M., Jonkers, M., Peeters, E.J., Korte-Bouws, G.A.H., Dederen, J.P., Kiliann, A.J., Martens, G.J., Schubert, D., Homberg, J.R. (2011). Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring. Psychopharmacology, 217, 419–432.                                                                                                                                                                         
Pitten, F.A., Kramer, A., Herrmann, K., Bremer, J., Koch, S., 2000. Formaldehyde neurotoxicity in animal experiments. Pathol. Res. Pract, 196, 193–198.
Quillfeldt, J.A. (2016). Behavioral Methods to Study Learning and Memory in Rats. Springer International Publishing Switzerland, 271–311.
Sorg, B.A., Hochstatter, T. (1999). Behavioral Sensitization After Repeated Formaldehyde Exposure in Rats. Toxicology and Industrial Health, 15, 346–355.
Tang, X.Q., Ren, Y.K., Chen, R.Q., Zhuang, Y.Y., Fang, H.R., Xu, J.H., Wang, C.Y., Hu, B. (2012). Hydrogen sulfide prevents formaldehyde-induced neurotoxicity to PC12 cells by attenuation of mitochondrial dysfunction and pro-apoptotic potential . Neurochemistry International 61, 16–24.
Tong, Z., Han, C., Qiang, M., Wang, W., Lv, J., Zhang, S., Luo, W., Li, H., Luo, H., Zhou, J., Wu, B., Su, T., Yang, X., Wang, X., Liu, Y., He, R. (2015). Age-related formaldehyde interferes with DNA methyltransferase function, causing memory loss in Alzheimer’s disease, Neurobiology of Aging xxx, 1–11.
Unasmaz, S.E., Akarsu, E.S., Vular, Nevin. (2002). Neurotoxic Effects of Acute and Subacute Formaldehyde Exposures in Mice. Environmental Toxicology and Pharmacology, 11, 93–100.
Wang, F., Li, C., Liu, W., Jin, Yihe. (2014). Potential mechanisms of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose VOCs. Inhal Toxicol, 2014; 26(4), 250–258.
Yang, M., Lu, J., Miao, J., Rizak, J., Yang, J., Zhai, R., Zhou, J., Qu, J., Wang, J., Yang, S., Ma, Y., Hu, X., He, R. (2014). Alzheimer’s Disease and Methanol Toxicity (Part 1): Chronic Methanol Feeding Led to Memory Impairments and Tau Hyperphosphorylation in Mice. Journal of Alzheimer’s Disease, 41, 1117–1129.
Zang, Z. J., Fang, Y.Q., Ji, S.Y., Gao, Y., Zhu, Y.Q., Xia, T.T., Jiang, M.H., Zhang, Y.N. (2017). Formaldehyde Inhibits Sexual Behavior and Expression of Steroidogenic Enzymes in the Testes of Mice. J Sex Med, 14, 1297–1306.