Evaluation of the effects of herpes symplex proteins on the complement system, cytokines and epigenetic changes in in vitro models of alzheimer's disease

Alzheimer's disease (AD) is characterized by decline in cognitive functions and dementia. Most cases are sporadic. However, some of these cases may develop from genetic or epigenetic origins. Additionally, it has been stated that dysregulation of complement proteins or cytokines expressed in the brain may also be a factor in the development of AD. On the other hand, there is data that pathogens such as Herpes simplex 1 (HSV-1) may also contribute to the development of AD. Within the scope of this thesis, we aimed to determine the effect of HSV-1 glycoprotein B (HSV-gB) by evaluating the complement proteins, cytokine levels and epigenetic changes in the cells by creating two different AD models in the SH-SY5Y cell line, a neuroblastoma cell line. According to the results obtained from cytotoxicity experiments, the inhibitory concentration 20 (IC20) dose for HSV-gB was found to be 190.5 pg/ml. Study groups (n=3) were designed as: 1. control; 2. HSV group; 3. retinoic acid (RA) and brain derived neurotrophic factor induced (BDNF) Alzheimer's model (AD), 4. RA and BDNF induced alzheimer's model + HSV-gB (ADH), 5. amyloid beta 1-42 peptide induced Alzheimer's model (Aβ) and 6. amyloid beta 1-42 peptide induced Alzheimer's model + HSV-gB (AβH). Specific AD markers (hyperphosphorylated Tau proteins, Aβ 1-42 peptide and amyloid precursor protein) were measured in all groups. HSV-gB administration was found to increase Aβ and hyperphosphorylated Tau levels, similar to AD models. Levels of complement proteins and cytokines were determined comparatively in all groups. In addition, epigenetic parameters (DNA methylation, histone modifications and histone deacetylase levels) were evaluated in the study groups. As a result of the evaluation of the results obtained, it has been shown that the immune system and chronic inflammation may have very important roles in the development of the disease and that HSV-1 infection may be an underlying factor of AD. It was also determined that epigenetic dysregulation may be effective in the development of AD and that HSV-1 infection may contribute to the pathogenesis of the disease by this mechanism.