Elsevier

Experimental Neurology

Volume 292, June 2017, Pages 11-20
Experimental Neurology

Research Paper
Asymmetric dopaminergic degeneration and levodopa alter functional corticostriatal connectivity bilaterally in experimental parkinsonism

https://doi.org/10.1016/j.expneurol.2017.02.014Get rights and content
Under a Creative Commons license
open access

Highlights

  • Rats unilaterally lesioned with 6-hydroxydopamine (6-OHDA) are examined using MRI.

  • Diffusion MRI revealed loss of fractional anisotropy in a lesioned substantia nigra.

  • rs-fMRI showed lower functional connectivity (FC) btw intact and lesioned striata.

  • FC increased between the lesioned striatum and both sensorimotor cortices.

  • Levodopa normalized FC between sensorimotor cortices and lesioned striatum.

Abstract

Asymmetric dopamine loss is commonly found in early Parkinson's disease (PD), but its effects on functional networks have been difficult to delineate in PD patients because of variations in age, disease duration and therapy. Here we used unilateral 6-hydroxydopamine-lesioned (6-OHDA) rats and controls and treated them with a single intraperitoneal injection of levodopa (L-DOPA) before performing diffusion weighted MRI and resting state functional MRI (rs-fMRI). In accordance with a neurodegeneration of the nigrostriatal dopaminergic pathway, diffusion tensor imaging showed increased radial diffusivity and decreased fractional anisotropy in the lesioned substantia nigra. Likewise a deterministic connectometry approach showed increase of isotropic diffusion values in the medial forebrain bundle. rs-fMRI showed reduced interhemispheric functional connectivity (FC) between the intact and the 6-OHDA lesioned caudate-putamen. Unexpectedly, there was an increased FC between the 6-OHDA lesioned caudate-putamen and sensorimotor cortices of both hemispheres. L-DOPA reversed the FC changes between the dopamine denervated caudate-putamen and the sensorimotor cortices, but not the reduced interhemispheric FC between caudate-putamina. Similarly, L-DOPA induced c-fos expression in both sensorimotor cortices, but only in the dopamine-depleted caudate-putamen. Taken together, these data suggest that asymmetric degeneration of the nigrostriatal dopamine pathway results in functional asynchrony between the intact and 6-OHDA-lesioned caudate-putamen and increased interhemispheric synchrony between sensorimotor cortices. The results also indicate that the initial effect of L-DOPA is to restore functional corticostriatal connectivity rather than synchronize caudate-putamina.

Abbreviations

6-OHDA
6-hydroxydopamine
CPu
caudate putamen
DAT
dopamine transporter
DTI
diffusion tensor imaging
dw-MRI
diffusion weighted MRI
FA
fractional anisotropy
FC
functional connectivity
FOV
field of view
GQI
generalized Q-ball imaging
iso
isotropic value of the diffusion orientation density function
L-DOPA
levodopa
MFB
medial forebrain bundle
MRI
magnetic resonance imaging
PD
Parkinson's disease
QSDR
Q-space diffeomorphic reconstruction
RD
radial diffusivity
ROI
region of interest
rs-fMRI
resting-state functional MRI
SSC
sodium chloride–sodium citrate buffer.

Keywords

Parkinson's disease
Resting-state functional MRI
Diffusion weighted MRI
6-Hydroxydopamine
Animal model
Diffusion tensor imaging

Cited by (0)