Microarray analysis of the PVN of spontaneously hypertensive wistar rats (SHR)

The paraventricular nucleus (PVN) of the hypothalamus is a key autonomic regulation area in the brain known to influence sympathetic nerve activity. Identified neurons project from the PVN to the spinal cord and can modulate cardiac function (Coote JH 1995). The PVN has been linked to cardiovascular diseases such as hypertension, where an elevation in sympathetic nerve activity is observed (Guyenet PG 2006 and Zhang K et al . 2002). For example, the activity of ‘spinally projecting’ PVN neurons is altered in models of heart failure (Patel KP 2000) and lesioning of the PVN prevents the development of spontaneous hypertension in SHRs (Takeda K et al. 1991). In this study, we performed transcriptome analysis of tissue from the PVN of 4 SHR and 4 normal Wistar Kyoto rats. In brief, tissue was isolated by 2mm diameter tissue punch from the dorsal PVN, homogenised and RNA extracted with Qiagen RNAeasy minikits in accordance with the manufactures instructions. The highest quality scoring 3 normal and 3 SHR were then analysed with an Illumina Beadchip microarray. Data was analysed in MatLab. Log2 normalised expression sets were created and genes with low absolute expression values or variance were filtered out (lowest 10%) (Kohane, I. et al . 2003). Significant differential transcription was then identified with an all permutation (t‐test). FDR and correct “q‐values” were created following the methods of Storey et al. 2003. Significantly increased/decreased genes were subjected to biological function enrichment analysis using PANTHER. Both PCA (PC1 vs PC2) and cluster analysis showed complete separation of the SHR and normotensive populations and 1592 genes in total were differentially expressed by more than 1.3 fold (and q‐value <0.05). Of particular interest to autonomic control of cardiovascular function was the enriched clusters of genes associated with circulatory control (AVP, angiotensin and Substance P, and the α‐1B adrenergic receptor), however, some genes associated with “inflammaging” were also differentially expressed such as superoxide dismutase 1 enzyme (SOD) and Il1b. Our results illustrate that there are distinct PVN‐specific changes in gene expression that occur in spontaneously hypertensive rats. In particular, we show that genes important in circulatory control and fear/stress responses are enriched in the PVN, further supporting a role for the PVN in cardiovascular diseases. Further experiments are needed to verify the functionality of these changes in gene expression, such as brain‐slice electrophysiology and whole‐animal experiments. The results of these experiments will be crucial in understanding the role of PVN in cardiovascular diseases such as hypertension. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .