SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson's disease

Ashkan, Keyoumars; Wallace, Bradley A.; Mitrofanis, John; Pollo, Claudio; Brard, Pierre-Yves; Fagret, Daniel; Benabid, Alim‐Louis

doi:10.1016/j.parkreldis.2006.10.009

Cited by 32 publications

(20 citation statements)

References 44 publications

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“…Finally, NIr light treatment has been shown to improve recovery from optic axonal degeneration (Assia et al, 1989;Desmet et al, 2006), together with ischemic heart injury (Oron et al, 2001), wound healing , and stroke (Lampl et al, 2007). A consistent finding among previous studies is that with greater dopaminergic cell death after parkinsonian insult, then the smaller the magnitude of neuroprotection (e.g., Ashkan et al, 2007;Wallace et al, 2007). This feature is evident in our results in the SNc.…”

Section: Comparison With Previous Experimental Studiessupporting

confidence: 90%

Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment

Shaw

Spana

Ashkan

et al. 2009

J of Comparative Neurology

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126

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This study explores whether near-infrared (NIr) light treatment neuroprotects dopaminergic cells in the substantia nigra pars compacta (SNc) and the zona incerta-hypothalamus (ZI-Hyp) from degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. BALB/c albino mice were divided into four groups: 1) Saline, 2) Saline-NIr, 3) MPTP, 4) MPTP-NIr. The injections were intraperitoneal and they were followed immediately by NIr light treatment (or not). Two doses of MPTP, mild (50 mg/kg) and strong (100 mg/kg), were used. Mice were perfused transcardially with aldehyde fixative 6 days after their MPTP treatment. Brains were processed for tyrosine hydroxylase (TH) immunochemistry. The number of TH(+) cells was estimated using the optical fractionator method. Our major finding was that in the SNc there were significantly more dopaminergic cells in the MPTP-NIr compared to the MPTP group (35%-45%). By contrast, in the ZI-Hyp there was no significant difference in the numbers of cells in these two groups. In addition, our results indicated that survival in the two regions after MPTP insult was dose-dependent. In the stronger MPTP regime, the magnitude of loss was similar in the two regions ( approximately 60%), while in the milder regime cell loss was greater in the SNc (45%) than ZI-Hyp ( approximately 30%). In summary, our results indicate that NIr light treatment offers neuroprotection against MPTP toxicity for dopaminergic cells in the SNc, but not in the ZI-Hyp.

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Section: Comparison With Previous Experimental Studiessupporting

confidence: 90%

Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment

Shaw

Spana

Ashkan

et al. 2009

J of Comparative Neurology

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126

121

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“…there was an obvious imbalance be- tween the left and the right. The behaviors were also similar those in the 6-OHDA and MPTP animal models of PD [36,37] , further indicating an asymmetry of the DA circuit in the nigra-striatal tract. In the present study, we also investigated in detail for the first time time-dependent cataplasia of behaviors, which were in keeping with late progressive characteristics of PD.…”

Section: Behavioral Changes After Lactacystin Treatmentsupporting

confidence: 59%

Nigral Degeneration with Inclusion Body Formation and Behavioral Changes in Rats after Proteasomal Inhibition

Niu

Mei

Pan³

et al. 2009

Stereotact Funct Neurosurg

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Objective: We were interested in studying nigral degeneration with inclusion body formation and behavioral changes in rats after proteasomal inhibition. Methods: Observation of progressive behavioral and pathological changes in rats following a unilateral nigral injection of lactacystin, a selective proteasome inhibitor. Results: After administration at a concentration of 10 μg (2 μl) of lactacystin, when tyrosine hydroxylase (TH) immunostaining decreased gradually in the substantia nigra pars compacta (SNc) and corpus striatum, α-synuclein-immunopositive inclusion appeared extensively in the surviving neurons. We also observed the degeneration of diverse cellular organelles by transmission electron microscopy. The effect of cellular organelle degeneration on behavior, a clinical index, was striking and was statistically significant. Over the 3 weeks following the administration of lactacystin, a highly significant decrease in TH immunostaining was observed and α-synuclein-immunopositive inclusions gradually appeared. Interestingly, there was a strong correlation in behavioral changes and the increase in α-synuclein-immunopositive inclusions whereas the decrease in TH immunostaining did not seem to induce any behavioral changes. Conclusions: Our results reveal that unilateral nigral proteasome inhibition induces degeneration in the SNc and corpus striatum as well as behavioral changes demonstrating strong time dependence. Behavioral changes were driven by the formation of α-synuclein inclusions, but not by decreased TH neurons.

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“…This may be in line with the suggested pattern of an exponential reduction of the dopaminergic neurons in the substantia nigra that has been proposed earlier [18]. This might in turn be reflected by the DAT uptake in the striatal regions according to the suggested correlation between nigrostriatal degeneration and dopamine terminal dysfunction [19]. Previous in-vivo functional imaging studies have also reported faster decline rates in dopamine terminal dysfunction in early-stage PD compared with later-stage disease [20].…”

Section: Discussionsupporting

confidence: 85%

Long-term dopamine transporter imaging in Parkinson’s disease treated with zona incerta stimulation

Lindér

Blomstedt

et al. 2016

Nuclear Medicine Communications

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SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson's disease

Cited by 32 publications

References 44 publications

Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment

Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment

Nigral Degeneration with Inclusion Body Formation and Behavioral Changes in Rats after Proteasomal Inhibition

Long-term dopamine transporter imaging in Parkinson’s disease treated with zona incerta stimulation

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