Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/- mice were protected from degeneration. As well, there was a significant attenuation of weight loss and improved motor behavior. TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-SMN mediated pathway. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice. Trichostatin A (TSA is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. The Smn-independent beneficial effects of trichostatin A on an intermediate mouse model of spinal muscular atrophy.ĭirectory of Open Access Journals (Sweden)įull Text Available Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Since low level of survival motor neuron protein is bound to disease severity in SMA, the robust increase in protein level produced by lithium provides solid evidence which calls for further investigations considering lithium in the long-term treatment of spinal muscle atrophy. These data demonstrate that long-term lithium administration during a long-lasting motor neuron disorder attenuates behavioural deficit and neuropathology. In SMA-III mice long-term lithium administration determines a dramatic increase of survival motor neuron protein levels in the spinal cord. In addition, lithium prevents motor neuron enlargement and motor neuron heterotopy and suppresses the occurrence of radial-like glial fibrillary acidic protein immunostaining in the ventral white matter of SMA-III mice. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course. This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/- SMN1A2G+/- SMN2+/+) of Spinal Muscle Atrophy type III ( SMA-III). Protective effects of long-term lithium administration in a slowly progressive SMA mouse model.īiagioni, Francesca Ferrucci, Michela Ryskalin, Larisa Fulceri, Federica Lazzeri, Gloria Calierno, Maria Teresa Busceti, Carla L Ruffoli, Riccardo Fornai, Francesco
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