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  2. Anti-depressant effect of cerebrolysin in reserpine-induced depression in rats: Behavioral, biochemical, molecular and immunohistochemical evidence

Anti-depressant effect of cerebrolysin in reserpine-induced depression in rats: Behavioral, biochemical, molecular and immunohistochemical evidence

  • Chem Biol Interact. 2021 Jan 25:334:109329. doi: 10.1016/j.cbi.2020.109329.
Salma A El-Marasy 1 Sally A El Awdan 2 Azza Hassan 3 Omar A Ahmed-Farid 4 Hanan A Ogaly 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, National Research Centre, Giza, Egypt. Electronic address: [email protected].
  • 2 Department of Pharmacology, National Research Centre, Giza, Egypt.
  • 3 Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
  • 4 Department of Physiology, National Organization for Drug Control and Research, Giza, Egypt.
  • 5 Department of Chemistry, College of Sciences, King Khalid University, Abha, Saudi Arabia; Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Abstract

Depression is a major psychological disorder that contributes to global health problem. This study aimed to evaluate the anti-depressant effect of Cerebrolysin (CBL) in Reserpine-induced depressed rats, its effect on oxidative stress, inflammation, regulatory cyclic AMP-dependent response element binding protein (CREB)/brain derived neurotropic factor (BDNF) signaling pathways, brain monoamines and histopathological changes was assessed. Rats received either the vehicle or Reserpine (0.5 mg/kg, i.p.) for 14 days. The other three groups were pretreated with CBL (2.5, 5 ml/kg; i.p.) or fluoxetine (FLU) (5 mg/kg, p.o.), respectively for 14 days, 30 min before reserpine injection. Then analyses were conducted. CBL reversed Reserpine-induced reduction in latency to immobility and prolongation of immobility time in the forced swimming test (FST), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced tumor necrosis factor-alpha (TNF-ɑ), and elevated BDNF cortical and hippocampal brain contents. CBL elevated protein kinase A (PKA) and nuclear factor kappa-B (NF-κB) cortical and hippocampal protein expressions. CBL also ameliorated alterations in mRNA expressions of protein kinase B (Akt), CREB and BDNF in the cortical and hippocampal tissues. CBL elevated nor-epinephrine (NE), serotonin (5-HT), and dopamine (DA) and reduced 5-Hydroxyindoleacetic acid (5-HTAA), 3,4-Dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) cortical and hippocampal contents. CBL effects were in parallel to those observed with the standard anti-depressant drug, FLU. This study shows that CBL exerted anti-depressant effect evidenced by attenuation of oxidative stress and inflammation as well as enhancement of neurogenesis, amelioration of monoaminergic system and histopathological changes.

Keywords

Anti-depressant; Brain monoamines; Cerebrolyin; Inflammation; Regulatory CREB/BDNF signaling Pathway; Reserpine.

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