From 3 weeks of age, TDP-43WTxQ331K mice displayed a rapid decline in their motor function, with a significant reduction in performance on the accelerating rotarod at 5 weeks of age compared with non-transgenic, TDP-43WT and TDP-43Q331K littermates (Fig. 2a).
From 4 weeks, hFUS mice displayed a failure to gain weight normally (Fig. 2a, e) and a rapid decline in their motor function, displaying a significant reduction in performance on the accelerating rotarod compared with NTg and hFUS littermates (Fig. 2b).
We also previously reported a similar profile of decreased motor function as demonstrated by the reduction in stereotypy following the administration of the JWH015 compound the three mouse strains [18].
Strauss et al. [ 35] found a decline in walking ability from 20 years and Jahnsen et al. [ 17] observed a reduction in gross motor function in adults at GMFCS II III, mostly as a result of lack of balance, fear of falling, pain, and exhaustion.
Motor function, sensory function, and functional performance were also assessed.
A modest reduction in sensory and motor function was also observed in six month-old diabetic Ins2Akita/+ mice [37].
In these cases a substantial reduction of cognitive and motor function as well as sympathetic counterregulation is observed [ 17].
Even in cases of less severe hypoglycaemia a substantial reduction of cognitive and motor function as well as hormonal counter regulation is observed [ 1].
Furthermore, the Phase II clinical trial for lamotrigine (Na+ channel blocker), on secondary progressive MS patients showed exacerbation in motor function abnormalities, which were reverted upon a reduction in the lamotrigine dose [ 98].
Thus, a major challenge for the clinical use of cannabinoids, i.e. as an anti-fibrogenic therapy, will be the reduction of these cognitive, affective and motor function side-effects [47], [50].
