Plastic Changes in the Spinal Cord in Motor Neuron Disease

Abstract

In the present paper, we analyze the cell number within lamina X at the end stage of disease in a G93A mouse model of ALS; the effects induced by lithium; the stem-cell like phenotype of lamina X cells during ALS; the differentiation of these cells towards either a glial or neuronal phenotype. In summary we found that G93A mouse model of ALS produces an increase in lamina X cells which is further augmented by lithium administration. In the absence of lithium these nestin positive stem-like cells preferentially differentiate into glia (GFAP positive), while in the presence of lithium these cells differentiate towards a neuron-like phenotype (βIII-tubulin, NeuN, and calbindin-D28K positive). These effects of lithium are observed concomitantly with attenuation in disease progression and are reminiscent of neurogenetic effects induced by lithium in the subependymal ventricular zone of the hippocampus.

Compartment-dependent mitochondrial alterations in experimental ALS, the effects of mitophagy and mitochondriogenesis

“…This limits the analysis to phasic alpha motor neurons ruling out gamma motor neurons and most tonic alpha motor neurons, but it guarantees to rule out type I Golgi projecting neurons. This size-exclusion criterion is validated by several previous studies adjusted to various mouse strains (Morrison et al, 1998 ; Martin et al, 2007 ; Fornai et al, 2008a , 2014 ; Ferrucci et al, 2010 ; Fulceri et al, 2012 ).…”

“…All treatments started at 67 days of age, which corresponds to a pre-symptomatic stage, and they were carried out every other day up to a tetraplegic stage (end point), when mice were sacrificed with deep anesthesia (chloral hydrate). The tetraplegic stage was defined when mice were no longer able to get up from a lying position within a 30 s time interval (Parone et al, 2013 ; Fornai et al, 2014 ). This end point was chosen in order to avoid discomfort due to impaired feeding, drinking and breathing (Tankersley et al, 2007 ; Fornai et al, 2014 ).…”

“…The tetraplegic stage was defined when mice were no longer able to get up from a lying position within a 30 s time interval (Parone et al, 2013 ; Fornai et al, 2014 ). This end point was chosen in order to avoid discomfort due to impaired feeding, drinking and breathing (Tankersley et al, 2007 ; Fornai et al, 2014 ). Lithium chloride (Sigma, St. Louis, MO, USA) was administered (both to G93A and WT mice) at the dose of 1 mEq/Kg, i.p.…”

Neuroplasticity and Repair in Rodent Neurotoxic Models of Spinal Motoneuron Disease

“…Interestingly, a pattern of NPCs proliferation and reactive gliosis closely resembling that found in CTB-Sap models, with no evidence of neurogenesis, was found in transgenic mouse models of ALS expressing the mutated human SOD1 gene [ 109 , 110 ]. Unfortunately, further information concerning these endogenous repairing potentials of ALS affected SC is still lacking, and the results provided by neurotoxic models are therefore of great importance.…”

“…As previously discussed, NPCs proliferation occurs in different animal models of motoneuron loss, including neurotoxic and ALS models, but external interventions are needed to potentiate this capacity and drive NPCs differentiation towards the neuronal phenotype [ 66 , 109 , 110 ]. Bambakidis and colleagues (2003) have treated SC lesioned rats with Shh and provided evidence of increased NPCs proliferation and their differentiation as oligodendrocytes and neurons [ 73 , 155 ].…”