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Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection

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A Correction to this article was published on 16 November 2021

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Abstract

Various studies have indicated a lower incidence and prevalence of neurological conditions in people consuming curcumin. The ability of curcumin to target multiple cascades, simultaneously, could be held responsible for its neuroprotective effects. The present study was designed to investigate the potential of curcumin in minimizing microglia-mediated damage in lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and increased inflammatory profile of the CNS have severe behavioral consequences. In the current investigation, a single injection of LPS (5 ug/5 µl PBS) was injected into the substantia nigra (SN) of rats, and curcumin [40 mg/kg b.wt (i.p.)] was administered daily for a period of 21 days. LPS triggered an inflammatory response characterized by glial activation [Iba-1 and glial fibrillary acidic protein (GFAP)] and pro-inflammatory cytokine production (TNF-α and IL-1β) leading to extensive dopaminergic loss and behavioral abnormality in rats. The behavioral observations, biochemical markers, quantification of dopamine and its metabolites (DOPAC and HVA) using HPLC followed by IHC of tyrosine hydroxylase (TH) were evaluated after 21 days of LPS injection. Curcumin supplementation prevented dopaminergic degeneration in LPS-treated animals by normalizing the altered levels of biomarkers. Also, a significant improvement in TH levels as well as behavioral parameters (actophotometer, rotarod, beam walking and grid walking tests) were seen in LPS injected rats. Curcumin shielded the dopaminergic neurons against LPS-induced inflammatory response, which was associated with suppression of glial activation (microglia and astrocytes) and transcription factor NF-κB as depicted from RT-PCR and EMSA assay. Curcumin also suppressed microglial NADPH oxidase activation as observed from NADPH oxidase activity. The results suggested that one of the important mechanisms by which curcumin mediates its protective effects in the LPS-induced PD model is by inhibiting glial activation. Therefore, curcumin could be a potential therapeutic agent for inflammation-driven neurodegenerative disorders like PD, and its neuroprotective role should be explored further.

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Abbreviations

AD:

Alzheimer’s disease

DA:

Dopamine

DCFH-DA:

2′-7′-Dichlorordihydrofluorescein diacetate

GFAP:

Glial fibrillary acidic protein

HD:

Huntington’s chorea

IL-1β:

Interleukin-1β

MDA:

Malondialdehyde

NF-κB:

Nuclear factor-κB

NADPH oxidase:

Nicotinamide adenine dinucleotide phosphate-oxidase

NO:

Nitric oxide

LPO:

Lipid peroxidation

LPS:

Lipopolysaccharide

PD:

Parkinson’s disease

PHOX:

Phagocytic oxidase

PMF:

Post-mitochondrial fraction

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SN:

Substantia nigra

TH:

Tyrosine hydroxylase

TNF-α:

Tumor necrosis factor-alpha

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Acknowledgement

The study was carried out with the funds provided by Indian Council of Medical Research (ICMR) India (Grant No. 45/52/2013-PHA/BMS).

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  1. Department of Biophysics, Panjab University, Chandigarh, 160014, India

    Neha Sharma, Sheetal Sharma & Bimla Nehru

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  1. Neha Sharma
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Correspondence to Bimla Nehru.

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Sharma, N., Sharma, S. & Nehru, B. Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection. Inflammopharmacol 25, 351–368 (2017). https://doi.org/10.1007/s10787-017-0346-z

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