Akademik Veri Yönetim Sistemi
Tezin Türü: Doktora
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye
Tezin Onay Tarihi: 2012
Öğrenci: ÇİĞDEM GÖKÇEK SARAÇ
Danışman: ORHAN ADALI
Özet:Despite very extensive studies related to molecular processes underlying memory formation, still little known about the potential differences in the brain biochemistry between “good” and “poor” learners belonging to a random population of young animals. In the present study, an attempt was taken to correlate the individual variation in short- and long-term spatial memory in three different lines of young, healthy rats: inbred Wistar (W), outcrossed Wistar/Spraque Dawley (W/S) and pigmented Long-Evans rats, with hippocampal levels of selected enzymes known as “memory molecules” including neuronal (n), endothelial (e) and inducible (i) NOS, CaMKIIα, PKA and ChAT. Additionally, in order to indirectly estimate the activity of CaMKIIα and PKA, hippocampal levels of their phosphorylated forms (pCaMKIIα and pPKA) were assessed. Rats were classified as “good” and “poor” learners on the basis of their performance in a partially baited 12-arm radial maze. The hippocampal protein levels were measured using Western Blot technique. In addition to individual variation in animals’ learning capacity, strain-depended differences have also been observed. Deficient performance recorded in inbred W rats compared to outcrossed W/S rats, and “poor” learners from both rat groups had predominantly related to the higher frequency of reference memory errors. The results of biochemical assays showed strain-depended differences in the NOS expression. The overall NOS levels were significantly higher in outcrossed W/S rats compared to inbred W rats. In both rat lines, the rate of learning positively correlated with hippocampal levels of nNOS and negatively correlated with iNOS levels. Hippocampal eNOS levels correlated negatively with animals’ performance but only in the W rats. These results suggested that all 3 NOS isoforms are implemented in the learning process playing, however, different roles in neural signaling. Experiments carried out on Long-Evans rats did not reveal a significant difference in the basal hippocampal levels of the CaMKIIα, however, the level of the pCaMKIIα, was significantly higher in “good” learners. Also, hippocampal levels of both PKA and pPKA, as well as that of ChAT were significantly higher in “good” as compared to “poor” learners. Taken together, the latter findings indicate that low hippocampal expression of PKA and ChAT as well as low CaMKIIα or PKA activation may cause learning deficits in random population of young rats, and thus, these enzymes can be considered target molecules when looking for cognitive enhancers to treat memory deficits in young subjects.