Dataset Information

Simultaneous Measurement of Striatal Dopamine and Hydrogen Peroxide Transients Associated with L-DOPA Induced Rotation in Hemiparkinsonian Rats.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder commonly treated with levodopa (L-DOPA), which eventually induces abnormal involuntary movements (AIMs). The neurochemical contributors to these dyskinesias are unknown; however, several lines of evidence indicate an interplay of dopamine (DA) and oxidative stress. Here, DA and hydrogen peroxide (H₂O₂) were simultaneously monitored at discrete recording sites in the dorsal striata of hemiparkinsonian rats using fast-scan cyclic voltammetry. Mass spectrometry imaging validated the lesions. Hemiparkinsonian rats exhibited classic L-DOPA-induced AIMs and rotations as well as increased DA and H₂O₂ tone over saline controls after 1 week of treatment. By week 3, DA tone remained elevated beyond that of controls, but H₂O₂ tone was largely normalized. At this time point, rapid chemical transients were time-locked with spontaneous bouts of rotation. Striatal H₂O₂ rapidly increased with the initiation of contraversive rotational behaviors in lesioned L-DOPA animals, in both hemispheres. DA signals simultaneously decreased with rotation onset. The results support a role for these striatal neuromodulators in the adaptive changes that occur with L-DOPA treatment in PD and reveal a precise interplay between DA and H₂O₂ in the initiation of involuntary locomotion.

SUBMITTER: Wilson LR

PROVIDER: S-EPMC9838821 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Simultaneous Measurement of Striatal Dopamine and Hydrogen Peroxide Transients Associated with L-DOPA Induced Rotation in Hemiparkinsonian Rats.

Wilson Leslie R LR Lee Christie A CA Mason Catherine F CF Khodjaniyazova Sitora S Flores Kevin B KB Muddiman David C DC Sombers Leslie A LA

ACS measurement science au 20211108 2

Parkinson's disease (PD) is a neurodegenerative disorder commonly treated with levodopa (L-DOPA), which eventually induces abnormal involuntary movements (AIMs). The neurochemical contributors to these dyskinesias are unknown; however, several lines of evidence indicate an interplay of dopamine (DA) and oxidative stress. Here, DA and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) were simultaneously monitored at discrete recording sites in the dorsal striata of hemiparkinsonian rats using fast-s ...[more]

PMID: 36785724

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Project description:Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are used extensively as a model of Parkinson's disease. The present experiments sought to identify genes that were affected in the dopamine (DA)-denervated striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal dopaminergic pathway in the rat. We also examined whether a single injection of methamphetamine (METH) (2.5 mg/kg) known to cause changes in gene expression in the normally DA-innervated striatum could still influence striatal gene expression in the absence of DA. Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle resulted in METH-induced rotational behaviors ipsilateral to the lesioned side and total striatal DA depletion on the lesioned side. This injection also caused decrease in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. DA depletion was associated with increases in 5-HIAA/5-HT ratios that were potentiated by the METH injection. Microarray analyses revealed changes (±1.7-fold, p<0.025) in the expression of 67 genes on the lesioned side in comparison to the intact side of the saline-treated hemiparkinsonian animals. These include follistatin, neuromedin U, and tachykinin 2 which were up-regulated. METH administration caused increases in the expression of c-fos, Egr1, and Nor-1 on the intact side. On the DA-depleted side, METH administration also increased the expression of 61 genes including Pdgf-d and Cox-2. There were METH-induced changes in 16 genes that were common in the DA-innervated and DA-depleted sides. These include c-fos and Nor-1 which show greater changes on the normal DA side. Thus, the present study documents, for the first time, that METH mediated DA-independent changes in the levels of transcripts of several genes in the DA-denervated striatum. Our results also implicate 5-HT as a potential player in these METH-induced alterations in gene expression because the METH injection also caused significant increases in 5-HIAA/5-HT ratios on the DA-depleted side.

Dataset Information

Simultaneous Measurement of Striatal Dopamine and Hydrogen Peroxide Transients Associated with L-DOPA Induced Rotation in Hemiparkinsonian Rats.

Publications

Simultaneous Measurement of Striatal Dopamine and Hydrogen Peroxide Transients Associated with L-DOPA Induced Rotation in Hemiparkinsonian Rats.

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