Microglial Inhibitory Mechanism of Coenzyme Q10 Against Aβ (1-42) Induced Cognitive Dysfunctions: Possible Behavioral, Biochemical, Cellular, and Histopathological Alterations.

Arti Singh,Anil Kumar

doi:10.3389/fphar.2015.00268

Abstract

Rationale: Alzheimer’s disease (AD) is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ) (1-42) is a reliable model of AD that recapitulates many aspects of human AD.Objective: The intent of the present study was to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10) and its modulation by minocycline (microglial inhibitor) against Aβ (1-42) induced cognitive dysfunction in rats.Method: Intrahippocampal (i.h.) Aβ (1-42) (1 μg/μl; 4μl/site) were administered followed by drug treatment with galantamine (2 mg/kg), CoQ10 (20 and 40 mg/kg), minocycline (50 and 100 mg/kg) and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE) level, proinflammatory markers (TNF-α), mitochondrial respiratory enzyme complexes (I-IV) and histopathological examinations were assessed.Results: Aβ (1-42) administration significantly impaired cognitive performance in Morris water maze (MWM) performance test, causes oxidative stress, raised AChE level, caused neuroinflammation, mitochondrial dysfunction and histopathological alterations as compared to sham treatment. Treatment with CoQ10 (20 and 40 mg/kg) and minocycline (50 and 100 mg/kg) alone for 21 days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ), reduced AChE activity, oxidative damage (reduced LPO, nitrite level and restored SOD, catalase and GHS levels), TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV) activities and histopathological alterations as compared to Aβ (1-42) treated animals. Further, combinations of minocycline (50 and 100 mg/kg) with CoQ10 (20 and 40 mg/kg) significantly modulates the protective effect of CoQ10 dose dependently as compared to their effect alone.Conclusion: The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia inhibitory mechanism along with its mitochondrial restoring and anti-oxidant properties.

Highlights

Alzheimer’s disease (AD) is a slow growing neurodegenerative disorder, caused significant cognitive dysfunction worldwide (Hampel et al, 2011)
Treatment with Coenzyme Q10 (CoQ10) (20 and 40 mg/kg) and minocycline (50 and 100 mg/kg) alone for 21 days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ), reduced AChE activity, oxidative damage, TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV) activities and histopathological alterations as compared to Aβ (1-42) treated animals
The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia inhibitory mechanism along with its mitochondrial restoring and anti-oxidant properties

Summary

Introduction

Alzheimer’s disease (AD) is a slow growing neurodegenerative disorder, caused significant cognitive dysfunction worldwide (Hampel et al, 2011) It causes progressive loss of mental, behavioral, functional deficits and ability to learn (Braak and Del Tredici, 2012). It accounts for more than 36 million people worldwide suffering from this slow growing deadly disease (Anand et al, 2014; Association, 2014). The amyloid plaques are primarily composed of amyloid beta (Aβ) (1-42) peptide. This peptide aggregates to form dimers and oligomers which are the principal toxic species that leads to neuronal death (Christensen et al, 2008)

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