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Objective: In neurons, trans-acting RNA-binding proteins regulate splicing, polyadenylation, stability and transport at axons and dendrites. Their misregulation or functional disruption due to mutations or sequestration into nuclear or cytoplasmic inclusions have been linked to pathogenesis of several neuropsychiatric and neurodegenerative disorders. In this study, we aimed to create an animal model by using virus-mediated gene transfer to induce proteinopathic changes in neurons. Methods: Adeno-Associated Virus (AAV) serotype-9 is used to design construction of a casette encoding TarDNA binding protein- 43 (TDP43) expression. The control plasmid is comprised sequences for replication and structural proteins, green fluorescent protein (GFP), polyadenylation signal driven by cytomegalovirus (CMV) promoter between two inverted terminal repeats, while the transgene plasmid is additionally included wild-type TDP43 sequences. Systemic delivery of viruses to rats (n=3 for each age) were done throughout diverse injection sites at different ages. Facial and tail veins were used in neonatal (postnatal day 3) and adult (postnatal day 80) animals, respectively. Phenotypic changes were followed by walking pattern and rota-rod tests. Results: In neonatal animals, motor deficits observed two weeks after injections. Hindpaw withdrawal reflex was disturbed in all CMV-TDP43-GFP-injected animals. Due to the excessive weight loss, muscle weakness and respiratory problems animals were perfused on postnatal day '5. Adult animals survived without a major motor deficit. Their motor performances were examined with regular intervals by rota-rod test between P80- P350. No significant difference was found between CMVTDP43- GFP and CMV-GFP-injected animals. Conclusion: Discoveries of new AAV vectors crossing bloodbrain barrier have made gene transfer possible to adult animals by intravascular injections. However, timing of injection significantly influences the biodistribution of AAV. Neonatal injections result in widespread expression in the central nervous system, but transduction is quite limited in adult animals. Therefore, manufacturing improvements are still necessary for translational gene therapy paradigms. [ABSTRACT FROM AUTHOR]