Regional NMDA receptor density in AD and control subjects measured with [³H]MK801 autoradiography.

<div><p>A. Representative autoradiographic and anatomical images. </p> <p>Top –Hippocampal anatomy is shown on the left followed by a representative pseudocolored NMDAR autoradiogram from hippocampus of a control subject and a representative autoradiogram from hippocampus of a subject with AD. The bottom row depicts striatal anatomy on the left followed by a representative NMDAR autoradiogram from a control striatum and a representative autoradiogram from a subject with AD. Autoradiograms were pseudocolored using the rainbow spectrum (bar on the right).</p> <p>B. Quantitative autoradiographic measurements of regional NMDAR density (expressed as specific binding of [³H]MK801 in nCi/mg tissue).</p> <p>Abbreviations: CA1-4 cornu ammoni fields of the hippocampus, DG=gentate gyrus, SubP=subpyramidal layers of CA1(including stratum radiatum, lacunosum, and moleculare),, Sub=subiculum, ECx=entorhinal cortex, Str=striatum. </p> <p>*p<0.05, **p<0.005 AD relative to control; ANOVA followed by Fisher’s PLSD posthoc test. </p> <p>C. NMDAR density in the CA1 pyramidal layer as a function of Braak stage (left) and genotype (right). </p> <p>*p<0.05 relative to Braak stages 0-II, one way ANOVA followed by Fisher’s PLSD posthoc test.</p> <p>**p<0.005, student’s t test. </p></div

Regional TSPO mRNA gene expression in relation to AD pathology and ApoE genotype.

<div><p>A. TSPO gene expression by region and disease state. TSPO mRNA gene expression was measured by RT-PCR and expressed as fold change over expression in the reference sample. **p<0.005.</p> <p>B. TSPO gene expression as a function of Braak stage in hippocampus (left) and striatum (right).</p> <p>*p<0.05 relative to Braak stages 0-II, one way ANOVA followed by Fisher’s PLSD posthoc test.</p> <p>C. Effect of genotype on TSPO gene expression in hippocampus (left) and striatum (right).</p> <p>*p<0.05, students t-test 2 tailed.</p></div

Regional neuroinflammation in AD subjects and controls measured with [³H]PK11195 autoradiography.

<div><p>A. Representative autoradiographic and anatomical images. </p> <p>Top –Hippocampal anatomy is shown on the left followed by a representative pseudocolored TSPO autoradiogram from hippocampus of a control subject and a representative autoradiogram from hippocampus of a subject with AD. The bottom row depicts striatal anatomy on the left followed by a representative TSPO autoradiogram from a control striatum and a representative autoradiogram from a subject with AD. </p> <p>Autoradiograms were pseudocolored using the rainbow spectrum (bar on the right).</p> <p>B. Quantitative autoradiographic measurements of regional TSPO density (expressed as specific binding of [3H]PK11195 in nCi/mg tissue).</p> <p>Abbreviations: CA1-4 cornu ammoni fields of the hippocampus, DG=gentate gyrus, SubP=subpyramidal layers of CA1, Sub=subiculum, ECx=entorhinal cortex, Str=striatum. </p> <p>*p<0.05, **p<0.005 AD relative to control; ANOVA followed by Fisher’s PLSD posthoc test. </p> <p>C. TSPO density in CA1 pyramidal cell body layer as a function of Braak stage (left) and genotype (right). </p> <p>*p<0.05 relative to Braak stages 0-II, one way ANOVA followed by Fisher’s PLSD posthoc test.</p> <p>**p<0.005, student’s t test. </p></div

Region dependent correlation between TSPO and NMDAR density.

<div><p>Quantitative analyses of [³H]MK801 binding to NMDAR and [³H]PK11195 binding to TSPO were performed by autoradiography. The correlation between NMDAR and TSPO density was negative in the CA1 hippocampal field (left, <i>n</i> = 38, Spearman’s <i>p</i> < 0.001) and positive in the striatum (right, <i>n</i> = 37, Spearman’s <i>p</i> < 0.001).</p> <p>SB=specific binding.</p></div

Additional file 4: Figure S3. of A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations

A-to-I RNA editing in oocytes, AMY and PFC of adult female rats. Editing sites where % editing are high are presented in the top part of the figure; sites where % editing are low (0–4%) are presented in the bottom part. N’s, PFC, 11, AMY 12, Oocytes 5–12. (TIFF 584 kb

Additional file 1: Figure S1. of A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations

A Flow chart of sample preparation using the Illumina-based Htr2c-direcetd NGS. (PDF 92 kb

Additional file 2: Table S1. of A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations

RNA editing sites detected with mmPCR-seq. Table S2. Primer sequences used for mmPCR-seq, Real-Time PCR and Htr2c-directed NGS. Table S3. % RNA editing in PFC and AMY of neonatal (P0) vs. adult (P60) rats. Table S4. Age-dependent changes in Htr2c isoform prevalence in PFC and AMY. Table S5. % RNA editing in neonatal (P0) and adult (P60) PFC vs. AMY. Table S6. Htr2c and ADARs correlations with significant non-synonymous editing sites. Table S7. Changes in Htr2c isoform prevalence in PFC vs. AMY at P0 and P60. Table S8. The effects of PRS on RNA editing at learning- and stress-related genes in F0, F1 and F2. Table S9. Statistical analysis of editing differences between oocytes, PFC and AMY. (XLSX 92 kb