The effects of stress and menopause on learning

Öz

Aim: In this study, we aimed to to investigate the co-effect of stress and menopause on the learning ability in rats. Methods: 60 female Wistar-Albino rats were used in this study and were randomly divided into four groups (15 rats per group) as follows: Control group (Group I), experimental immobilization stress model (Group II), experimental menopause model (Group III), and experimental menopause model + experimental stress model (Group IV). Long-term cognitive and motor abilities of all rats were evaluated by conducting behaviour experiments (open field and morris water maze test). Furthermore, the gene expression of corticosteroid receptor (glucocorticoid receptor and mineralocorticoid receptor) was examined by Real-Time PCR using SYBR Green followed by mRNA isolation and cDNA synthesis. Results: In the comparison study of in-group time for attaining mean elevation over days, it was detected that time for attaining mean elevation was statistically significantly shorter than previous day from 1^st day to 4^th(p<0.001). There was no statistically significance for daily time for mean elevation among the groups (p>0.05). In the open area experiment, although the Group II exhibited shorter mean when comparing the progressed distances, but the difference among the groups was not statistically significant (p>0.05). Gene expression of both glucocorticoid receptor and mineralocorticoid receptor in the hipocampal tissue was determined to be lower in comparison with the control group. However, this decrease was not statistically significant (p>0.05). Conclusion: This result shows that acute immobilization stres and experimental menopause model is not efficient on the learning ability in rats. 

Anahtar Kelimeler

• Stress,menopause,learning,hypothalamus-pituitary-adrenal axis

Stres ve menopozun öğrenme üzerindeki etkileri

Öz

Amaç: Bu çalışmada stres ve menopozun birlikte, öğrenme işlevi üzerindeki etkileri araştırılmıştır. Yöntem: Çalışmada, 60 adet dişi Wistar-Albino sıçan kullanılmıştır. Bu sıçanlar randomize olarak kontrol (Grup I), deneysel immobilizasyon stres modeli (Grup II), deneysel menopoz modeli (Grup III) ve deneysel menopoz modeli + deneysel stres modeli (Grup IV) olmak üzere her bir grupta 15’er hayvan bulunan 4 gruba ayrılmıştır. Tüm sıçanların uzun dönemdeki bilişsel ve motor yetileri davranış deneyleri (açık alan ve Morris su tankı) ile değerlendirilmiştir. Ayrıca hipotalamus-hipofiz-adrenal ekseninin geribildirim işlevinde merkezi konumunda olan kortikosteroid reseptör (Glukokortikoid reseptörü ve mineralokortikoid reseptörü) gen ekspresyonu mRNA izolasyonu ve cDNA sentezi takibinde SYBR Green kullanılarak eş zamanlı PCR yöntemiyle incelenmiştir. Bulgular: Tüm grupların kendi içinde günlere göre ortalama yükseltiyi bulma sürelerinin karşılaştırmasında, birinci günden 4. güne kadar, tüm gruplarda her günün ortalama yükseltiyi bulma sürelerinin bir önceki günden istatistiksel olarak anlamlı düzeyde kısa olduğu saptanmıştır (p<0.001). Güne göre yükseltiyi bulma sürelerinin gruplar arasında karşılaştırmasında istatistiksel olarak anlamlı bir fark saptanmamıştır (p>0.05). Açık alan deneyinde ortalama katedilen mesafenin gruplara göre karşılaştırmasında grup II en düşük ortalamaya sahip olmasına karşın, gruplar arasında istatistiksel olarak anlamlı bir fark bulunamamıştır (p>0.05). Hipokampal dokuda hem glukokortikoid reseptörünün hem de mineralokortikoid reseptörünün gen ekspresyonu tüm gruplarda kontrol grubuna kıyasla düşük bulunmuştur. Ancak bu düşüş istatistiksel olarak anlamlı bulunamamıştır (p>0.05). Sonuç: Bu sonuç akut immobilizasyon stresin ve deneysel menopoz modelinin öğrenme üzerinde etkili olmadığını düşündürmüştür.

Anahtar Kelimeler

• Stres,menopoz,öğrenme,hipotalamus-hipofiz-adrenal aksı,kortikosteroid reseptörleri

Kaynakça

1. 1) Lupien SJ, Juster RP, Raymond C, Marin MF. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Front Neuroendocrinol 2018;49:91-105. 2) Tamer Ş. Stres Fizyolojisi. Yiğit R. Genel Fizyoloji, İÜ, İstanbul Tıp Fakültesi., Temel ve Klinik Bilimler Ders Kitapları, Nobel Tıp Kitabevi 2001:29-39. 3) Herman JP, Ostrander MM, Muelle NK, Figueiredo H. Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocorticol axis. Prog Neuropsychopharmacol Biol Psychiatry 2005:29(8):1201-1213. 4) De Cloet ER, Vreugdenhil E, Oitzl MS, Joels M. Brain corticosteroid receptor balance and homeostatic control. Frontiers Neuroendocrinol 1991;12(2):95-164. 5) De Cloet ER, Vreugdenhil E, Oitzl MS, Joels M. Brain corticosteroid receptor balance in healt and disease. Endocr Rev 1998;19(3):269-301. 6) Heck AL, Handa RJ. Sex differences in the hypothalamic-pituitary-adrenal axis' response to stress: an important role for gonadal hormones. Neuropsychopharmacology 2019;44(1):45-58. 7) Sunstrum JK, Inoue W. Heterosynaptic modulation in the paraventricular nucleus of the hypothalamus. Neuropharmacology 2018;3908(18):30841-30844. 8) Sawada H, Shimohama S. Neuroprotective effects of estradiol in mesencephalic dopaminergic neurons. Neurosci Biobehav Rev.2000; 24(1):143-147. 9) Han F, Ding J, Shi Y. Expression of amygdala mineralocorticoid receptor and glucocorticoid receptor in the single-prolonged stress rats. BMC Neurosci 2014;15(1):77. 10) Tsujita Y, Muraski J, Shiraishi I, Kato T, Kajstura J, Anversa P, Sussman MA. Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy. Proc Natl Acad Sci USA 2006;103(32):11946-51. 11) KD Ehman, VC Moser. Evaluation of cognitive function in weanling rats: A review of methods suitable for chemical screening. Neurotoxicology and Teratology 2006;28(1):144-161. 12) Agrawal R, Tyagi E, Saxena G, Nath C. Cholinergic influence on memory stages: A study on scopolamine amnesic mice. Indian J Pharmacol 2009;41(4):192-196. 13) Feng EC, Jiang L. Effects of leptin on neurocognitive and motor functions in juvenile rats in a preterm brain damage model. Mol Med Rep 2018;18(4):4095-4102. 14) Biedermann SV, Biedermann DG, Wenzlaff F, Kurjak T, Nouri S, Auer MK, Wiedemann K, Briken P, Haaker J, Lonsdorf TB, Fuss J. An elevated plus-maze in mixed reality for studying human anxiety-related behavior. BMC Biol 2017;15(1):125. 15) Ikeda T, Mishima K, Aoo N, Harada K, Liu AX, Egashira N, Iwasaki K, Fujiwara M, Ikenoue T. Rehabilitative training tasks ımprove spatial learning impairment in the water maze following hypoxic-ischemic insult in neonatal rats. Ped Research 2006;59(1):61-5. 16) Lieben CK.J, Oorsouw KV, Deutz NEP, Blokland A. Acute tryptophan depletion induced by a gelatin-based mixture impairs object memory but not affective behavior and spatial learning in the rat. Behav Brain Res 2004;151(1-2):53-64 17) A Ennaceur, S Michalikova, PL Chazot. Models of anxiety: Responses of rats to novelty in an open space an enclosed space. Behav Brain Res 2006;171(1):26-49. 18) Pereria LO, Arteni NS, Peterson RC, Padilha da Rocha A, Achaval M, Netto CA. Effects of daily environmental enrichment on memory deficits and brain injury following neonatal hypoxia-ischemia in the rat. Neurobiology of Learning and Memory 2007;87(1):101-8. 19) Ikeda T, Mishima K, Aoo N. Combination treatment of neonatal rats with hypoxiaischemia and endotoxin induces long-lasting memory and learning impairment that is associated with extended cerebral damage. Am J of Obst and Gynecology 2004;191(6); 2132-41. 20) D’ Hooger D, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Rev 2001;36(1):60-90. 21) Bramham CR. Control of synaptic consolidation in the dentate gyrus: mechanisms, functions, and therapeutic implications. Prog Brain Res 2007;163:453-71.