Fig 2: Validation of several targets of the differential miRNAs. (A) Transcription levels of Rbm8a, SYT7, HTR1B, RTN4, and SV2A were measured by qPCR. (B) Protein levels of Rbm8a, SYT7, HTR1B, RTN4, and SV2A were determined by western blotting.

Fig 3: Changes in synaptic protein expression in R237H rats. A, B, Western analysis of pre- and postsynaptic proteins SV2A and PSD95, respectively, in the hippocampus. Representative images are shown for immunoblots and corresponding protein stain from the same region of the gel with molecular weight marker positions indicated on the right. Values for each protein are normalized to total protein and expressed as a fraction of the WT group. C, D, Western analysis of excitatory pre- and postsynaptic markers VGluT1 and GluA1 (E, F) and inhibitory markers VGAT and gephyrin. Data were analyzed with a two-tailed unpaired t test, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, N = 5 males, and 5 females at 8 weeks of age for each group.

Fig 4: Longitudinal SV2A quantification. (a) VT(IDIF) parametric maps for wild-type (WT) and heterozygous (HET) mice aged 3 months (3 M) and 6 months (6 M). (b) VT(IDIF) quantification and evaluation of WT/HET differences at 3 M and 6 M of age. Mixed effects model analysis. n = 22–24 per genotype and age. Abbreviations: striatum (STR), motor cortex (MC), hippocampus (HIP), thalamus (THAL), cerebellum (CB).

Fig 5: Ex vivo analyses. (a) [3H]SynVesT-1 exemplary image and SV2A quantification for wild-type (WT) and heterozygous (HET) zQ175DN mice (n = 15 WT, 14 HET). Standard series in nCi/mg reported on figure. (b) [3H]UCB-J exemplary image and SV2A quantification (n = 14 WT, 14 HET except THAL HET n = 13) for WT and HET zQ175DN mice. Standard series in nCi/mg reported on figure. Exemplary images from panel 5a and 5b were obtained from the same male WT mouse (adjacent brain slices). (c) Exemplary images of the striatum (STR) and cortex (CTX) obtained through immunofluorescent (IF) SV2A staining and quantification of SV2A as percentage (%) positive area through IF staining (n = 15 WT, 15 HET). CTX and STR WT n = 13 for SV2A IF. Both exemplary images in panel c originate from the same male WT mouse. Scale bar: 200 µm. Statistics: multiple unpaired t-tests for all graphs. Abbreviations: striatum (STR), cortex (CTX), hippocampus (HIP), thalamus (THAL).