Objective: To assess if a microglial modulator, Glatiramer Acetate (GA), can restore loss of striatal dopamine (DA) and behavioral deficits following progressive 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) lesioning.

Background: Patients with Parkinson’s disease have increased inflammatory response as the disease progresses. A component of this inflammatory response is not only the activation of microglia, but also an increased shift towards pro-inflammatory microglia (m1) compared to the anti-inflammatory (m2) subtypes. A reversal of this shift could be therapeutically relevant in PD by allowing recovery of nigrostriatal DA.

Methods: Mice (C57BL/6J, male, 12 weeks) were injected with MPTP for 4 weeks with increasing doses (10, 20, 24, and 32mg/kg, i.p., 5 d/wk). After 4 weeks of toxin administration, a group of animals were injected with 2 different dosages of GA: 1.5mg/kg or 3.5mg/kg, i.p. The remaining animals were injected with vehicle. Treatment with GA continued for 4 weeks, 7 days/week post MPTP administration. Behavioral measures were taken following GA treatment.

Results: Optical density for tyrosine hydroxylase (TH) in the striatum revealed a 65% loss of TH in the MPTP group compared to vehicle (p=<0.0001). There was a 13% loss of TH in the MPTP+GA group in the striatum compared to the vehicle group despite 4 weeks of MPTP administration (p=0.0191). Grip test analysis showed that the MPTP group had a 52% increase in grip strength compared to the vehicle group (p=<0.0001). The MPTP+GA group showed a 20% increase in grip strength compared to vehicles (p=0.0003). Microglial markers typifying the two subtypes showed no changes between the vehicle or MPTP groups. Interestingly, IBA1, a marker of activated microglia, showed a 60% increase in the MPTP group compared to the vehicle group (p=0.0352), while the MPTP+GA group showed no increase in IBA-1 expression compared to the vehicle group (p=0.4864).

Conclusions: These data suggest that post-MPTP treatment with GA resulted in restoration of TH within the striatum and recovery in grip strength. However the data suggest that the restoration observed was not caused by a shift of from m1 to m2 subtypes, but rather a decrease in the activation of microglia.

7,8 dihydroxyflavone, a tyrosine receptor kinase B agonist, slows the loss of striatal dopamine nerve terminals in a progressive mouse model of Parkinson’s disease.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/glatiramir-acetate-copaxone-causes-restoration-of-the-striatal-dopamine-in-a-progressive-mptp-mouse-model-of-parkinsons-disease/