Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory decline: Implication of oxidative stress and cholinergic impairment

Kantar Gok D., Hidisoglu E., OCAK G. A., ER H., Acun A. D., Yargıçoğlu P.

NEUROCHEMISTRY INTERNATIONAL, ss.1-13, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.neuint.2018.04.008
  • Dergi Adı: NEUROCHEMISTRY INTERNATIONAL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus
  • Sayfa Sayıları: ss.1-13
  • Anahtar Kelimeler: Amyloid beta, Rosmarinic acid, Lipid peroxidation, Antioxidant system, Cholinergic system, Auditory event-related potential, ANTIOXIDANT ENZYME-ACTIVITY, MILD COGNITIVE IMPAIRMENT, ALZHEIMERS-DISEASE BRAIN, EVENT-RELATED POTENTIALS, AUDITORY SENSORY MEMORY, MISMATCH NEGATIVITY, REACTIVE SUBSTANCES, SENILE-DEMENTIA, IN-VITRO, DYSFUNCTION
  • Akdeniz Üniversitesi Adresli: Evet

Özet

In the present study, we examined whether rosmarinic acid (RA) reverses amyloid beta (A beta) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), A beta 42 peptide (A beta) and A beta 42 peptide + RA (A beta R) groups. Rat model of Alzheimer was established by bilateral injection of A beta 42 peptide (2,2 nmol/10 mu l) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection. At the end of the experimental period, we recorded the auditory event related potentials (AERPs) and mismatch negativity (MMN) response to assess auditory functions followed by histological and biochemical analysis. A beta 42 injection led to a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4-Hydroxy-2-nonenal (4-HNE) but decreased the activity of antioxidant enzymes (SOD, CAT, GSH-Px) and glutathione levels. Moreover, A beta 42 injection resulted in a reduction in the acetylcholine content and acetylcholine esterase activity. RA treatment prevented the observed alterations in the A beta R group. Furthermore, RA attenuated the increased A beta staining and astrocyte activation. We also found that A beta 42 injection decreased the MMN response and theta power/coherence of AERPs, suggesting an impairing effect on auditory discrimination and echoic memory processes. RA treatment reversed the A beta 42 related alterations in AERP parameters. In conclusion, our study demonstrates that RA prevented A beta-induced antioxidant oxidant imbalance and cholinergic damage, which may contribute to the improvement of neural network dynamics of auditory processes in this rat model.