Sadeghian, M;
Mullali, G;
Pocock, JM;
Piers, T;
Roach, A;
Smith, KJ;
(2016)
Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's disease.
Neuropathology and Applied Neurobiology
, 42
(5)
pp. 423-435.
10.1111/nan.12263.
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Sadeghian_et_al-2015 Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's disease.pdf Download (1MB) | Preview |
Abstract
AIMS: Current therapies in Parkinson's disease mainly treat symptoms rather than provide effective neuroprotection. We examined the effects of safinamide (monoamine oxidase B and sodium channel blocker) on microglial activation and the degeneration of dopaminergic neurons in a rat model of PD in vivo, and on microglia in vitro. METHODS: Rats received unilateral stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle on day 0: The contralateral side served as control. Safinamide or vehicle was delivered from days 0 or 1, for 7 days, via sub-cutaneous mini-pumps. RESULTS: In vehicle-treated rats 6-hydroxydopamine caused a significant increase in the number of activated MHC-II(+) microglia compared with the contralateral side, and only 50% of the dopaminergic neurons survived in the ipsilateral SNc. In contrast, rats treated daily with safinamide 50 and 150 mg/ml (on day 0 or 1) exhibited a significantly reduced number of activated microglia (55% reduction at 150 mg/ml) and a significant protection of dopaminergic neurons (80% of neurons survived) (P < 0.001) compared with vehicle-treated controls. Rasagiline, a monoamine oxidase B inhibitor, and lamotrigine, a sodium channel blocking drug, also protected dopaminergic neurons, indicating that safinamide may act by either or both mechanisms. Safinamide also reduced the activation of microglial cells in response to lipopolysaccharide exposure in vitro. CONCLUSION: Safinamide therapy suppresses microglial activation and protects dopaminergic neurons from degeneration in the 6-hydroxydopamine model of PD, suggesting that the drug not only treats symptoms but also provides neuroprotection.
| Type: | Article |
|---|---|
| Title: | Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/nan.12263 |
| Publisher version: | http://dx.doi.org/10.1111/nan.12263 |
| Language: | English |
| Additional information: | Copyright © 2015 British Neuropathological Society. This is the peer reviewed version of the following article: [Sadeghian, M., Mullali, G., Pocock, J. M., Piers, T., Roach, A. and Smith, K. J. (2016), Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's disease. Neuropathology and Applied Neurobiology, 42: 423–435. doi: 10.1111/nan.12263], which has been published in final form at http://dx.doi.org/10.1111/nan.12263. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
| Keywords: | Parkinson's disease |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1339532 |
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