Morin decreases cortical pyramidal neuron degeneration via inhibition of neuroinflammation in mouse model of schizophrenia.

Abstract

Neuroinflammation plays a prominent role in the pathophysiology and progression of schizophrenia. Thus, suppression of neuroinflammation may retard the progression of the disease. This study was designed to investigate whether morin, a bioactive compound with antipsychotic-like activity could reduce biomarkers of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)- and ketamine (KET)-induced schizophrenic-like behavior in mice. Animals were treated once daily intraperitoneally with morin (100 mg/kg), haloperidol (1 mg/kg), risperidone (0.5 mg/kg), or saline (10 mL/kg) in combination with LPS (0.1 mg/kg) for 14 consecutive days. However, from days 8-14, overt schizophrenia-like episode was produced with i.p. injection of KET (20 mg/kg) once daily. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction and social-memory tests) and cognitive (Y-maze test) symptoms were assessed on day 14. Thereafter, the levels and expressions of biomarkers of neuroinflammation were estimated in the striatum (ST), prefrontal cortex (PFC) and hippocampus (HC) using spectrophotometry, ELISA and immunohistochemistry. The effects of morin on cortical pyramidal neurons were estimated using Golgi-impregnation staining technique. LPS in combination with KET significantly (p < 0.05) induced schizophrenia-like behaviors, which was attenuated by morin. Morin significantly (p < 0.05) decreased tumor necrosis factor-α, interleukine-6 levels and myeloperoxidase activity in the ST, PFC and HC of mice treated with LPS + KET. Moreover, morin reduced regional brain expressions of cyclooxygenase-2, inducible nitric oxide synthase and nuclear factor kappa-B, and also rescued loss of pyramidal neurons in the PFC. Taken together, these findings suggest that morin reduces schizophrenic-like symptoms induced by LPS + KET via mechanisms related to inhibition of the release of pro-inflammatory mediators and suppression of degeneration of cortical pyramidal neurons in mice.

• Authors: Benneth Ben-Azu, Adegbuyi Oladele Aderibigbe, Abayomi Mayowa Ajayi, Aya-Ebi Okubo Eneni, Itivere Adrian Omogbiya, Olatunde Owoeye, Solomon Umukoro, Ezekiel O Iwalewa
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 70 Pg. 338-353 (May 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30852289 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Flavonoids
• Inflammation Mediators
• Interleukin-6
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Ketamine
• morin
• Peroxidase

Topics

• Animals
• Antioxidants (therapeutic use)
• Behavior, Animal (drug effects)
• Cerebellar Cortex (cytology)
• Disease Models, Animal
• Flavonoids (therapeutic use)
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-6 (metabolism)
• Ketamine (metabolism)
• Lipopolysaccharides (metabolism)
• Male
• Mice
• Neurogenic Inflammation
• Peroxidase (metabolism)
• Pyramidal Cells (drug effects, physiology)
• Schizophrenia (drug therapy)
• Social Behavior
• Spinocerebellar Degenerations
• Tumor Necrosis Factor-alpha (metabolism)