UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's disease

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. Green open access

[img]
Preview
Text
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
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
Downloads since deposit
186Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item