The role of the tRNA methyltransferase FTSJ1 in the brain is largely unknown. We analyzed whether FTSJ1-deficient mice (KO) displayed altered neuronal plasticity. We explored open field behavior (10 KO mice (aged 22–25 weeks)) and 11 age-matched control littermates (WT) and examined mean layer thickness (7 KO; 6 WT) and dendritic spines (5 KO; 5 WT) in the hippocampal area CA1 and the dentate gyrus. Furthermore, long-term potentiation (LTP) within area CA1 was investigated (5 KO; 5 WT), and mass spectrometry (MS) using CA1 tissue (2 each) was performed. Compared to controls, KO mice showed a significant reduction in the mean thickness of apical CA1 layers. Dendritic spine densities were also altered in KO mice. Stable LTP could be induced in the CA1 area of KO mice and remained stable at for at least 1 h, although at a lower level as compared to WTs, while MS data indicated differential abundance of several proteins, which play a role in neuronal plasticity. FTSJ1 has an impact on neuronal plasticity in the murine hippocampal area CA1 at the morphological and physiological levels, which, in conjunction with comparable changes in other cortical areas, might accumulate in disturbed learning and memory functions.

Tissue sections, which are widely used in research and diagnostic laboratories and have already been examined by immunohistochemistry (IHC), may subsequently provide a resource for proteomic studies, even though only small amount of protein is available. Therefore, we established a workflow for tandem mass spectrometry-based protein profiling of IHC specimens and characterized defined brain area sections. We investigated the CA1 region of the hippocampus dissected from brain slices of adult C57BL/6J mice. The workflow contains detailed information on sample preparation from brain slices, including removal of antibodies and cover matrices, dissection of region(s) of interest, protein extraction and digestion, mass spectrometry measurement, and data analysis. The Gene Ontology (GO) knowledge base was used for further annotation. Literature searches and Gene Ontology annotation of the detected proteins verify the applicability of this method for global protein profiling using formalin-fixed and embedded material and previously used IHC slides.

Adult hippocampal neurogenesis is involved in hippocampal plasticity and can be enhanced by voluntary physical activity, which also elevates “brain-derived neurotrophic factor” (BDNF) levels and improves memory performance. BDNF might either be essential for the maintenance of neurogenesis, or be necessary for mediating activity-dependent increases in neurogenesis. In order to get more insight on this, we examined male heterozygous BDNF-deficient (BDNF +/−) mice with or without access to a running wheel. Only males were analyzed, since sex steroids can interact with BDNF signaling pathways. Although male BDNF +/− mice exhibited a higher body weight as compared to age-matched controls (BDNF +/+), they did not differ in distance traveled, running time or running speed. We then analyzed whether changes in adult hippocampal neurogenesis can be observed. Under housing conditions without running wheels, the rates of basal adult hippocampal neurogenesis were not altered between genotypes. Interestingly, voluntary wheel running significantly increased neurogenesis in both groups; however, the magnitude was attenuated in BDNF +/− mice. These results indicate that, in adult male mice, reduced BDNF availability does not impair basal adult hippocampal neurogenesis, but limits the plasticity-related enhancement of neurogenesis induced by physical activity.