Neuroprotective effects of pramipexole in young and aged MPTP-treated mice

Anderson, David W.; Neavin, T; Smith, J.A.; Schneider, Jay S.

doi:10.1016/s0006-8993(01)02466-0

Cited by 51 publications

(31 citation statements)

References 37 publications

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“…Our results are consistent with the previous reports and show that female mice are less susceptible to MPTP intoxication than their male counterparts [28,29] . We also found, in accordance with others [25,30,31] , that in young mice striatal TH content recovered at later time points.…”

Section: Discussionsupporting

confidence: 93%

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Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Ciesielska

Joniec

Kurkowska‐Jastrzębska

et al. 2007

Neuroimmunomodulation

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Objective: The neuroinflammatory reaction has been linked with Parkinson’s disease. One of the hypotheses to explain the significance of age and gender (male predominance) effects on neurodegeneration in Parkinson’s disease may result from a link between these risk factors and the inflammatory processes. Here, we investigated the expression of inflammatory mediators in relation to 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-induced neurodegenerative processes in nigrostriatal pathway in young and aged male and female mice.Methods and Results: We simultaneously assessed striatal tyrosine hydroxylase (TH) protein concentrations (Western blotting) and cytokine (TNFα, IFNγ, IL-1β, IL-6 and TGFβ₁) mRNA levels (RT-PCR) in young and aged (2- and 12-month-old) C57BL/6 male and female mice after 6 h, 1, 3, 7, 14, 21 days after MPTP intoxication.Western blotting analysis showed that at the early time points, males showed a greater reduction in striatal TH versus females. Additionally, in contrast to the aged mice, in young males and females the TH concentration gradually increased between the 7th and the 21st day after intoxication. The increases in TNFα, IL-1β and IFNγ after intoxication were faster in both young and aged males than females. In males (both ages), we observed an increase in TGFβ₁ at the early time points. In contrast, in females (both ages) TGFβ₁ was elevated at later time points. MPTP caused an increase in IL-6 in males and females, but this increase was significantly higher in females. Conclusions: A gender and age skewing of the cytokine gene expression in the striatum after intoxication may be related to the greater susceptibility in males as well as older animals to the detrimental effects of MPTP.

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Section: Discussionsupporting

confidence: 93%

“…It is well known that MPTP induces degeneration of TH-positive cells in the SN and loss of TH immunoreactivity of terminals in the striatum in both young and aged MPTP-treated mice [24][25][26] . The older mice show more pronounced decrease in dopaminergic cell loss induced by the same doses of MPTP treatment compared to young mice [27] .…”

Section: Discussionmentioning

confidence: 99%

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Ciesielska

Joniec

Kurkowska‐Jastrzębska

et al. 2007

Neuroimmunomodulation

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“…PPX was given at a lower dose of 3 mg/kg [shown to be neuroprotective in models of dopaminergic neurodegeneration (Zou et al, 2000;Anderson et al, 2001)] to test for putative neuroprotection in the ALS model, which might be mediated via activation of dopamine receptors.…”

Section: Targeted Antioxidative Neuroprotection By Pramipexole 193mentioning

confidence: 99%

Targeted Antioxidative and Neuroprotective Properties of the Dopamine Agonist Pramipexole and Its Nondopaminergic Enantiomer SND919CL2x [(+)2-Amino-4,5,6,7-tetrahydro-6-lpropylamino-benzathiazole Dihydrochloride]

Danzeisen

Schwalenstoecker²,

Gillardon³

et al. 2005

J Pharmacol Exp Ther

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Pramipexole has been shown to possess neuroprotective properties in vitro that are partly independent of its dopaminergic agonism. The site of neuroprotective action is still unknown. Using [3 H]pramipexole, we show that the drug enters and accumulates in cells and mitochondria. Detoxification of reactive oxygen species (ROS) by pramipexole is shown in vitro and in vivo by evaluating mitochondrial ROS release and aconitase-2 activity, respectively. Pramipexole and its (ϩ)-enantiomer

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“…[13][14][15][16] Neurobiological studies revealed an upregulation of the dopamine D3 receptor in the striatum of alcohol-preferring rats after one year of alcohol consumption. A repeated administration of the D3 agonist BP 897 (1) and the antagonist SB-277011A caused a significant dose-dependent decrease in the expression of behavioral effects induced by alcohol deprivation in rats.…”

Section: Introductionmentioning

confidence: 99%

¹⁸F‐Labeled FAUC 346 and BP 897 Derivatives as Subtype‐Selective Potential PET Radioligands for the Dopamine D3 Receptor

et al. 2008

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Disturbances of neutrotransmission at the dopamine D3 receptor are related to several neuropsychiatric diseases and in particular to drug addiction. Herein, we report the computer-assisted prediction of D3 selectivities of new fluoroalkoxy-substituted receptor ligands by means of 3D-QSAR analysis. As close analogues of the D3-selective lead compound FAUC 346 and BP 879, the (19)F-substituted test compounds 4 a-d were synthesized and evaluated. In vitro investigation of their binding characteristics in transfected Chinese Hamster Ovary (CHO) cells led to excellent K(i) values between 0.12 and 0.69 nM at the dopamine D3 subtype. The benzothiophene-substituted carboxamide 4 a (K(i)=0.12 nM) displayed 133 and 283-fold selectivity over the structurally related D2(Long) and D4 subtypes, respectively. Mitogenesis assays showed the behavior of partial agonists. Based on these data, we synthesized the [(18)F]fluoroethoxy-substituted radioligands [(18)F]4 a-d. The N-[4-[4-(2-hydroxyphenyl)piperazin-1-yl]butyl]-2-carboxamides 3 a-d were prepared and labeled with 2-[(18)F]fluoroethyltosylate in a two-step procedure. Optimization of the (18)F-labeling conditions led to radiochemical yields between 24 and 65 %.

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Neuroprotective effects of pramipexole in young and aged MPTP-treated mice

Cited by 51 publications

References 37 publications

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Targeted Antioxidative and Neuroprotective Properties of the Dopamine Agonist Pramipexole and Its Nondopaminergic Enantiomer SND919CL2x [(+)2-Amino-4,5,6,7-tetrahydro-6-lpropylamino-benzathiazole Dihydrochloride]

¹⁸F‐Labeled FAUC 346 and BP 897 Derivatives as Subtype‐Selective Potential PET Radioligands for the Dopamine D3 Receptor

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Neuroprotective effects of pramipexole in young and aged MPTP-treated mice

Cited by 51 publications

References 37 publications

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Targeted Antioxidative and Neuroprotective Properties of the Dopamine Agonist Pramipexole and Its Nondopaminergic Enantiomer SND919CL2x [(+)2-Amino-4,5,6,7-tetrahydro-6-lpropylamino-benzathiazole Dihydrochloride]

18F‐Labeled FAUC 346 and BP 897 Derivatives as Subtype‐Selective Potential PET Radioligands for the Dopamine D3 Receptor

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¹⁸F‐Labeled FAUC 346 and BP 897 Derivatives as Subtype‐Selective Potential PET Radioligands for the Dopamine D3 Receptor