Naslov
Expression of amyloid precursor protein (APP) and its processing enzymes in overweight/obese rats with altered serotonergic homeostasis

Autori
Zandl-Lang, Martina ; Kesić, Maja ; Albrecher, Nicole Maria ; Panzenboeck, Ute ; Čičin-Šain, Lipa ; Štefulj, Jasminka

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

Izvornik
6th Croatian Neuroscience Congress : Abstracts / - Zagreb, 2017, 86-86

Skup
6th Croatian Neuroscience Congress

Mjesto i datum
Osijek, Hrvatska, 16.09.2017. - 18.09.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
serotonin ; obesity ; amyloid precusor protein ; Wistar-Zagreb 5HT rats

Sažetak
Introduction: The development of amyloid-beta (Aβ) plaques is a crucial event in the pathogenesis of Alzheimer‘s disease (AD). Aβ is formed by sequential cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1) and the γ-secretase complex consisting of presenelin1 (PSEN1) and nicastrin (NCSTN) as the main components. Alternatively, APP can be processed by the α-secretase (ADAM10) which cleaves APP in the middle of the Aβ domain, precluding thus formation of amyloidogenic peptides. Multiple lines of evidence implicate serotonin (5-hydroxytryptamine, 5HT) in the development of AD. Also, a complex link between body mass index (BMI) and AD has been described. Here we explored expression of APP and its processing enzymes in the Wistar-Zagreb 5HT (WZ-5HT) rat, an animal model with altered 5HT homeostasis and body weight regulation. Methods: High-5HT (hyperserotonergic) and low-5HT (hyposerotonergic) sublines of the WZ-5HT rat were developed by selective breeding towards naturally occurring extremes of platelet 5HT parameters. BMI and serum cholesterol levels were determined in animals from both sublines. In the pharmacological experiment, rats were treated for 27 days with selective serotonin reuptake inhibitor (SSRI) fluoxetine (6 mg/kg, i. p.). Gene expression analyses were performed in the hypothalamus, cortex and visceral adipose tissue by the use of reverse transcription - quantitative polymerase chain reaction (RT-qPCR) based on SyberGreen technology. Results: High-5HT rats had higher body weight and BMI as well as elevated serum cholesterol levels as compared to low-5HT rats. Further, animals from the high-5HT subline displayed reduced APP expression in the hypothalamus while no differences between sublines were found in the cortex and visceral adipose tissue. Treatment of animals with fluoxetine did not alter cortical expression of APP in either of the sublines. On the other hand, fluoxetine reduced cortical expression of ADAM10, PSEN1, and NCSTN in low-5HT rats, but showed no statistically significant effect in high-5HT rats. In addition, low-5HT rats displayed increased cortical expression of the 5HT receptor type 4 (HTR4) in response to fluoxetine treatment, while cortical expression of the 5HT receptor type 2A (HTR2A) in both sublines was unaltered by fluoxetine treatment. Conclusion: Our results suggest a tissue-specific role of 5HT in regulating APP mRNA levels and indicate importance of the endogenous 5HT tone in mediating effects of 5HT-related drugs on APP processing. Further studies will address roles of 5HT and BMI in amyloidgenesis in greater detail.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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