Naslov
Stress and neuroinflammation as possible mediators of acute cognitive dysfunction in a streptozotocin-induced rat model of sporadic Alzheimer’s disease

Autori
Babić Perhoč, Ana ; Homolak, Jan ; Knezović, Ana ; Osmanović Barilar, Jelena ; Šalković-Petrišić, Melita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the WASAD Congress 2019: an International Congress of the World Association for stress related and anxiety disorders in collaboration with the Collaborative Research Center SFB-TRR 58, Fear, Anxiety, Anxiety Disorders, held on 3–5 October 2019 in Würzburg, Germany / - : Springer, 2019, 1525-1526

Skup
International Congress of the World Association for stress related and anxiety disorders (WASAD 2019)

Mjesto i datum
Würzburg, Njemačka, 03.10.2019. - 05.10.2019

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Alzheimer's disease ; stress ; streptozotocin ; cognitive dysfunction

Sažetak
Intracerebroventricular administration of streptozotocin (STZ-icv) induces insulin resistant brain state and cognitive dysfunction and is used to generate a non-transgenic model of sporadic Alzheimer's disease (sAD). Although stress is considered an important factor in the etiopathogenesis of sAD, its role in development of cognitive dysfunction in STZ-icv rat model has not been elucidated. Existing research has pointed to neuroinflammation as one of the early key factors in sAD pathology but the relationship between stress and neuroinflammation in the STZ-icv sAD model is yet to be established. The aim of this research is to explore the link between stress and neuroinflammation markers at 3 different time points after the induction of sAD in the STZ- icv model. Male Wistar rats were treated with STZ-icv at the age of 3 months (3 mg/kg in 2 doses). Cognitive performance was assessed 1, 3 and 6 months after STZ-icv treatment by Morris Water Maze and Passive Avoidance test in 2 sets of experiments. Plasma corticosterone and insulin were measured by ELISA. Plasma glucose was measured spectrophotometrically. The expression of the glial fibrillary acidic protein (GFAP) as a marker of neuroinflammation in the brain was assessed by immunohistochemistry. STZ treated rats were cognitively impaired in all measured time points after STZ-icv treatment (p<0.05). Plasma corticosterone was increased 1 month after STZ-icv treatment compared to controls (+38.4% ; p<0.05). Afterwards, plasma corticosterone in STZ-icv animals showed a gradual decline over time and was found comparable to controls at 3 (+23.3% ; p=0.18) and 6 (+5.7% ; p=1.00) months. Plasma insulin was acutely decreased 1 month after STZ-icv treatment (-45.2% ; p<0.01), but returned to baseline and remained unaffected after 3 and 6 months. No differences were found in plasma glucose levels in either time point. Hippocampal GFAP expression was elevated 1 month after STZ-icv treatment (+45%, p<0.05) compared to controls, while it returned to baseline at 3 months post STZ-icv. However, a marked decrease in GFAP expression was noted in STZ-icv treated animals 6 months after the treatment compared to controls (-70%, p<0.05). The presented results suggest that acute and chronic STZ-induced cognitive dysfunction and neuropathological changes might be mediated by different mechanisms. Acute STZ-induced changes could be related to neuroinflammation and stress, while chronic cognitive impairment seems to develop in parallel with other neuropathological alterations, including the insulin-related signaling dysregulation, as suggested by literature data. Financed by HRZZ IP-09-2014-4639 and UKF 64/10. This publication was co-financed by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain” ; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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