CHARACTERIZATION OF EXPRESSION PATTERN OF SOMATOSTATIN 4 RECEPTOR IN THE MOUSE BRAIN

Abstract

Somatostatin is a cyclic neuropeptide which is expressed in brain regions related to pain‐ and mood regulation. It has 5 inhibitory G‐protein coupled receptors, and subtype 4 (sst4) mediates analgesic, anti‐inflammatory and antidepressant effects without endocrine actions. It was suggested to be a novel drug target for chronic neuropathic pain. However, its central nervous system distribution and mechanism of the inhibitory actions are not known due to the lack of specific antibody.We mapped sst4 expression using β‐galactosidase immunohistochemistry in the brain of Sst4 knockout (KO) mice where sst4 was replaced by the lacZ gene. Since KO mice are not appropriate for determining functional changes and co‐localization, we also performed ultrasensitive RNAscope‐based in situ hybridization and neurochemical characterization on formalin‐fixed, paraffin‐embedded coronal sections of wild type mice. Sst4 mRNA was also quantified by qPCR in the positive regions.Strong sst4‐related β‐galactosidase immunopositivity was detected in the hippocampus, moderate in the medial septum, amygdala, habenula in both sexes. Remarkably more intensive signal was seen in the primary somatosensory cortex of male mice compared to females. Sst4 mRNA was abundant in the hippocampal CA1 region, amygdala, spinal cord, sensory and motor cortices (layer 5). It was co‐localized with vesicular glutamate transporter 1 in most regions and choline‐acetyl transferase in the habenula. Sst4 mRNA was significantly higher in the dorsal root ganglia compared the spinal cord. These are the first data for sst4 expression in glutamatergic and cholinergic excitatory neurons of the nociceptive pathway. This might explain its unique value to simultaneously inhibit chronic pain and depression.Support or Funding InformationÚNKP17‐3‐III‐PTE‐166, GINOP‐2.3.3.‐15‐2016‐00050, GINOP‐2.3.3.‐15‐2016‐00048, EFOP‐3.6.2‐16‐2017‐00008, KTIA_NAP_13‐2‐2014‐0022, KTIA_NAP_13‐1‐2013‐0001, 207653/2018/FEKUTSTRATThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.