The major hallmark of Parkinson’s disease (PD) is the
degeneration of dopaminergic neurons in the substantia nigra (SN), which is
responsible for the core motor symptoms of PD. Currently, there is no cure for
PD, and its prevalence is increasing, prompting the search for novel
neuroprotective treatments. Neuroinflammation is a core pathological process in
PD, evident by increased inflammatory biomarkers in the SN and cerebrospinal
fluid. Interestingly, epidemiological studies have reported a reduced risk of PD
in users of non-steroidal anti-inflammatory drugs compared to non-users,
suggesting the neuroprotective potential of anti-inflammatory drugs. Therefore,
this study aimed to: (1) test the efficacy of novel oral formulations of
edaravone (EDR) and curcumin (CUR) (which possess anti-inflammatory and
anti-oxidative properties) to alleviate motor and non-motor symptoms, and
associated pathology in the intrastriatal lipopolysaccharide (LPS) model of PD;
(2) investigate the expression of proteins linked to familial PD and markers of
autophagy in the intrastriatal LPS model treated with EDR and CUR.
Fifty-two C57BL/6 mice were divided into 4 groups, namely; (1)
control + vehicle; (2) LPS + vehicle; (3) LPS + EDR (made in vehicle) and (4) LPS
+ CUR (made in vehicle). 10 g of LPS was administered
stereotaxically into the right striatum, and EDR and CUR treatments were
initiated 2-weeks after the LPS injections. Behavioural tests were carried out at
4- and 8-weeks after LPS injection followed by tissue collection at 8-weeks.
Intrastriatal administration of LPS induced motor deficits and
anxiety-like behaviours at 4- and 8-weeks, which were accompanied by astroglial
activation, increased protein expression of -synuclein, heat shock
cognate protein of 70 kDa (HSC-70) and Rab-10, and reduced levels of tyrosine
hydroxylase (TH) protein in the striatum. Additionally, LPS induced astroglial
activation in the olfactory bulb, along with changes in the protein expression of
HSC-70. The changes associated with EDR and CUR in the striatum and olfactory
bulb were not statistically significant compared to the LPS group.
Intrastriatal administration of LPS induced pathological
changes of PD such as motor deficits, reduced expression of TH protein and
increased -synuclein protein, as well as some alterations in proteins
linked to familial PD and autophagy in the olfactory bulb and striatum, without
pronounced therapeutic effects of EDR and CUR. Our results may suggest that EDR
and CUR lack therapeutic effects when administered after the disease process was
already initiated. Thus, our treatment regimen or the physicochemical properties of
EDR and CUR could be further refined to elevate the therapeutic effects of these
formulations.