title: Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose.
abstract: BACKGROUND
  Animal models designed to mimic certain features of Alzheimer's disease (AD) can help us to increase our understanding of the underlying mechanisms of disease. Previous studies have revealed that long-term D-galactose injection combined with ovariectomy results in pathophysiologic alterations associated with AD. Thus, the aim of the present study was to investigate the effects of rosmarinic acid (RA) administration on pathological changes associated with ovariectomy and D-galactose injection, which serve as a two-insult model for AD.
  
  
  METHODS
  One hundred female Wistar rats were divided into five equal groups: control (C), Sham (Sh), rosmarinic acid treated (R), ovariectomized rats treated with D-galactose (OD), ovariectomized rats treated with D-galactose and rosmarinic acid (ODR) groups. D-galactose (80 mg/kg/day) was administered by i.p. injection and RA (50 mg/kg/day) was given via gavage for 60 days. Open field and Y-maze tests were used to assess locomotor activity and short-term spatial memory, respectively. Biochemical and histopathological analyses of the brain tissue were performed.
  
  
  RESULTS
  Open field testing showed that the locomotor activity and exploratory behavior of rats were prominently impaired in the OD group as compared to the other studied groups. Similarly, Y-maze test results revealed a decrease of short-term spatial memory in the OD rats. A concomitant treatment with RA significantly restored altered locomotor activity and cognitive functions in the ODR group. Lipid peroxidation levels, cyclooxygenase-2 expression and prostaglandin E2 levels in the brain tissue were higher in the OD group and RA treatment inhibited these changes. AD-like histopathological alterations and amyloid b peptide (Ab) depositions were observed in the OD group. Normal cell structure and lower Ab depositions were observed in the ODR group compared with the OD group.
  
  
  CONCLUSIONS
  RA could have the potential to prevent some psychological and biochemical alterations of brain tissue found in a rat model of AD probably by attenuating lipid peroxidation and inflammatory response.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kantar Gok
authors.forename: Nihal
authors.initials: N
authors.lastname: Ozturk
authors.forename: Hakan
authors.initials: H
authors.lastname: Er
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
authors.forename: Necdet
authors.initials: N
authors.lastname: Demir
authors.forename: Narin
authors.initials: N
authors.lastname: Derin
authors.forename: Aysel
authors.initials: A
authors.lastname: Agar
authors.affiliation: Department of Biophysics, Akdeniz University, Faculty of Medicine, Arapsuyu, Antalya. pakkiraz@akdeniz.edu.tr.
authors.forename: Piraye
authors.initials: P
authors.lastname: Yargicoglu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D053630:Depsides / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D005690:Galactose; D000097123:Rosmarinic Acid
keywords: Alzheimer’s disease; COX-2; IHC; PGE2; amyloid beta; electron microscopy; estrogen deficiency; hippocampus; lipid peroxidation; rat; rosmarinic acid; short-term memory