Naslov
Adult neurogenesis in the hippocampus of streptozotocin intracerebroventricularly treated rats – an animal model for sporadic Alzheimer's disease

Autori
Sun, Ping ; Knezović, Ana ; Parlak, Milena ; Lee, Margeritha M ; Hua, Qian ; Riederer, Peter ; Šalković-Petrišić, Melita ; Schmitt, Angelika G

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

Skup
The 10th Göttingen meeting of the German Neuroscience Society

Mjesto i datum
Göttingen, Njemačka, 13.03.2013. - 16.03.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
neurogenesis; streptozotocin; Alzheimer's disease

Sažetak
The phenomenon of adult hippocampal neurogenesis (AN), the generation of functional neurons in the adult dentate gyrus of the hippocampus, has been shown to be active in humans. Therefore, it may provide a basis for neuronal replacement therapy in neurodegenerative diseases like Parkinson`s disease, stroke, amyotrophic lateral sclerosis and Alzheimer`s disease (AD). There is a big controversy in literature regarding the involvement of AN in AD etiopathology. Most AN studies have used transgenic mice with altered amyloid ß precursor protein levels. But, these animal models relate more to the familial form of AD and not to the sporadic form of AD (sAD), which accounts for 95% of sufferers. We have investigated AN in streptozotocin intracerebroventricularly (STZ icv) treated rats, which exhibit cognitive deficits following STZ icv treatment, and are proposed recently as an animal model of sAD. For our AN study using this sAD model rats were sacrificed 1 and 3 months after STZ icv treatment. The combination of BrdU incorporation with a survival time of approximately 4 weeks and its subsequent detection via immunohistochemistry has been included in this study. Additionally, usage of other antibodies recognizing different AN stages such as the proliferation marker MCM2 and the two markers for immature neurons NeuroD and DCX has allowed us to analyse AN thoroughly. For proper quantification we immunostained serial sections and used the Stereo Investigator software from MicroBrightField. As recent studies have pointed to different functions of the dorsal and ventral part of the hippocampus, we analysed them separately. The results have demonstrated that STZ icv treatment resulted in altered AN levels exclusively in the dorsal hippocampus, which is shown to have a preferential role in certain forms of learning and memory, and not in the ventral hippocampus. In this region, the total number of both, NeuroD as well as DCX positive cells, were shown to be significantly decreased in rats 3 months after STZ icv injections compared to rats 3 months after the vehicle icv treatment. Interestingly, STZ icv treatment didn`t result in altered number of NeuroD and DCX immunoreactive cells after one month. The quantification of BrdU and MCM2 positive cells is still in progress. In summary, we could reveal impaired adult neurogenesis in the hippocampus of STZ icv treated rats, which possibly relates to cognitive deficits observed in this non-transgenic sAD animal model.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA