Dataset Information


α-Synuclein Overexpression Increases Dopamine D2/3 Receptor Binding and Immune Activation in a Model of Early Parkinson's Disease.

ABSTRACT: Progressive degeneration of dopaminergic neurons, immune activation, and α-synuclein pathology characterize Parkinson's disease (PD). We previously reported that unilateral intranigral injection of recombinant adeno-associated viral (rAAV) vectors encoding wild-type human α-synuclein produced a rat model of early PD with dopamine terminal dysfunction. Here we tested the hypothesis that decreases in dopamine result in increased postsynaptic dopamine D2/D3 receptor expression, neuroinflammation, and reduced synaptic vesicle glycoprotein 2A (SV2A) density. Rats were injected with rAAV encoding α-synuclein or green fluorescent protein and subjected to non-pharmacological motor tests, before euthanization at 12 weeks post-injection. We performed: (1) in situ hybridization of nigral tyrosine hydroxylase mRNA, (2) HPLC of striatal dopamine content, and (3) autoradiography with [3H]raclopride, [3H]DTBZ, [3H]GBR12935, [3H]PK11195, and [3H]UCB-J to measure binding at D2/3 receptors, vesicular monoamine transporter 2, dopamine transporters, mitochondrial translocator protein, and SV2A, respectively. rAAV-α-synuclein induced motor asymmetry and reduced tyrosine hydroxylase mRNA and dopamine content in ipsilateral brain regions. This was paralleled by elevated ipsilateral postsynaptic dopamine D2/3 receptor expression and immune activation, with no changes to synaptic SV2A density. In conclusion, α-synuclein overexpression results in dopaminergic degeneration that induced compensatory increases in D2/3 binding and immune activation, recapitulating many of the pathological characteristics of PD.

PROVIDER: S-EPMC8698691 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC8185945 | BioStudies
| S-EPMC7826971 | BioStudies
2015-10-28 | GSE74382 | GEO
| S-EPMC9247077 | BioStudies
2019-01-01 | S-EPMC6629243 | BioStudies
| S-EPMC8373893 | BioStudies
| S-EPMC2851596 | BioStudies
2016-01-01 | S-EPMC5066835 | BioStudies
| S-EPMC7452525 | BioStudies
| S-EPMC3779594 | BioStudies