Dna meti̇ltransferaz i̇nhi̇bi̇törü RG108 ve hi̇ston deaseti̇laz i̇nhi̇bi̇törü tri̇kostati̇n a'nin nöri̇t geli̇şi̇mi̇nde epi̇geneti̇k etki̇leri̇ni̇n karşilaştirilmasi

Neuropathological characteristics of neurodegenerative disorders are atrophy or loss of specific neurons in the specific brain areas. The lack of regeneration is due to a combination of factors: death of injured neurons, reduced capacity of regeneration, lack of necessary trophic molecules to support growth, and the presence of an environment hostile for any growth line. Neuritogenic substances hold the promise of therapeutic efficacy in the treatment of neuronal injuries by the virtue of their ability to stimulate outgrowth of neurites from neuronal cells. Despite of their positive effects, administration of neurotrophic factors also has some disadvantages like, negligible entry through the blood brain barrier and destabilization by peripheral peptidases. Small-molecule products like epigenetic drugs, which can activate silenced genes, regulate chromatin remodelling and transcription, for eliciting neuritogenic activity or in combination with neurotrophic substances is currently been focused as an alternative approach. In this study, we aimed to compare the neurotrophic effects of two new epigenetic drugs on PC-12 Adh cell line, which are a histone deacetylase inhibitior Trichostatin A and a DNA methyltransferase inhibitor RG108. Cytotoxic effects of this drugs were determined by MTT assay. Cell differentiation, migration and invasion analysis were evaluated by real time cell analysis (RTCA DP) system according to changing in cell index values. Migration was also corroborated with morphological analysis. Matrix metalloproteinase-2 (MMP-2) amounts during neurite outgrowth was measured by ELISA technique. Finally, neurite outgrowth was observed with immunofluorescence staining and determined by neurite outgrowth analysis on PC-12 Adh cell line. Our results show that both Trichostatin A and RG108 have inducing effects on neuronal differentiation and neurite outgrowth in PC-12 Adh cell line in a combination with nerve growth factor. We found Trichostatin A more effective than RG108 on inducing cell differentiation, migration, invasion and neurite outgrowth.