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

• Published in: Neuropathology and applied neurobiology 2016-08, Vol.42 (5), p.423-435
• Main Authors: Sadeghian, Mona, Mullali, Gizem, Pocock, Jennifer M., Piers, Thomas, Roach, Arthur, Smith, Kenneth J.
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - pharmacology; Animals; Benzylamines - pharmacology; Dopaminergic Neurons - drug effects; Ecstasy; Male; Microglia - drug effects; Nerve Degeneration - drug therapy; Nerve Degeneration - pathology; Neuroprotective Agents - pharmacology; Parkinson's disease; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - pathology; Rats; Rats, Sprague-Dawley; Rodents
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/nan.12263

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