title: Locus Coeruleus Dysfunction in Transgenic Rats with Low Brain Angiotensinogen.
abstract: OBJECTIVE
  Transgenic TGR(ASrAOGEN)680 (TGR) rats with specific downregulation of glial angiotensinogen (AOGEN) synthesis develop cardiovascular deficits, anxiety, altered response to stress, and depression. Here, we evaluated whether these deficits are associated with alteration of the integrity of the noradrenergic system originating from locus coeruleus (LC) neurons.
  
  
  METHODS
  Adult TGR rats were compared to control Sprague Dawley rats in terms of the following: tissue levels of transcripts encoding noradrenergic markers, tissue tyrosine hydroxylase (TH) protein level, in vivo TH activity, density of TH-containing fibers, behavioral response to novelty, locomotor activity, and polysomnography.
  
  
  RESULTS
  TH expression was increased in the LC of TGR rats compared to controls. In LC terminal fields, there was an increase in density of TH-containing fibers in TGR rats that was associated with an elevation of in vivo TH activity. TGR rats also displayed locomotor hyperactivity in response to novelty. Moreover, polysomnographic studies indicated that daily paradoxical sleep duration was increased in TGR rats and that the paradoxical sleep rebound triggered by total sleep deprivation was blunted in these rats.
  
  
  CONCLUSIONS
  Altogether, these results suggest that disruption of astroglial AOGEN synthesis leads to cardiovascular, cognitive, behavioral, and sleep disorders that might be partly due to LC dysfunction.
authors.affiliation: INSERM U1028, CNRS UMR5292, University Claude Bernard Lyon 1, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|Institute for Epilepsy, IDEE, Lyon, France.|French Armed Forces Biomedical Research Institute, Bretigny-sur-Orge, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Ogier
authors.affiliation: EA 4173, University Lyon 1, Lyon, France.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bricca
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: INSERM U1028, CNRS UMR5292, University Claude Bernard Lyon 1, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|Institute for Epilepsy, IDEE, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bezin
mesh_terms: D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature; D016022:Case-Control Studies; D002531:Cerebellum / Q000473:pathology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012890:Sleep / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014851:Wakefulness / Q000235:genetics
chemical_list: D005904:Glial Fibrillary Acidic Protein; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D000808:Angiotensinogen; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase
keywords: Angiotensin; Astrocytes; Brainstem; Transgenic rats; Tyrosine hydroxylase