RT Journal Article
SR Electronic
T1 CB1 receptor affects cortical plasticity and response to physiotherapy in multiple sclerosis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e48
DO 10.1212/NXI.0000000000000048
VO 1
IS 4
A1 Francesco Mori
A1 Concetta Ljoka
A1 Carolina G. Nicoletti
A1 Hajime Kusayanagi
A1 Fabio Buttari
A1 Laura Giordani
A1 Silvia Rossi
A1 Calogero Foti
A1 Diego Centonze
YR 2014
UL http://nn.neurology.org/content/1/4/e48.abstract
AB Objectives: Therapeutic effects of physical therapy in neurologic disorders mostly rely on the promotion of use-dependent synaptic plasticity in damaged neuronal circuits. Genetic differences affecting the efficiency of synaptic plasticity mechanisms could explain why some patients do not respond adequately to the treatment. It is known that physical exercise activates the endocannabinoid system and that stimulation of cannabinoid CB1 receptors (CB1Rs) promotes synaptic plasticity in both rodents and humans. We thus tested whether CB1R genetic variants affect responsiveness to exercise therapy.Methods: We evaluated the effect of a genetic variant of the CB1R associated with reduced receptor expression (patients with long AAT trinucleotide short tandem repeats in the CNR1 gene) on long-term potentiation (LTP)–like cortical plasticity induced by transcranial magnetic theta burst stimulation (TBS) of the motor cortex and, in parallel, on clinical response to exercise therapy in patients with multiple sclerosis.Results: We found that patients with long AAT CNR1 repeats do not express TBS-induced LTP-like cortical plasticity and show poor clinical benefit after exercise therapy.Conclusions: Our results provide the first evidence that genetic differences within the CB1R may influence clinical responses to exercise therapy, and they strengthen the hypothesis that CB1Rs are involved in the regulation of synaptic plasticity and in the control of spasticity in humans. This information might be of great relevance for patient stratification and personalized rehabilitation treatment programs.AATn=AAT trinucleotide short tandem repeat; AMT=active motor threshold; ANOVA=analysis of variance; CB1R=cannabinoid CB1 receptor; CS=conditioning stimulus; DMD=disease-modifying drug; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; FDI=first dorsal interosseus muscle; FLAIR=fluid-attenuated inversion recovery; ICF=intracortical facilitation; ISI=interstimulus interval; iTBS=intermittent TBS; LICI=long-interval intracortical inhibition; LTP=long-term synaptic potentiation; MEP=motor evoked potential; MS=multiple sclerosis; NRS=Numerical Rating Scale; pp=paired-pulse; PT=physical therapy; RMT=resting motor threshold; RRMS=relapsing-remitting MS; SICF=short-interval intracortical facilitation; SICI=short-interval intracortical inhibition; TBS=theta burst stimulation; TMS=transcranial magnetic stimulation; TS=test stimulus; TSE=turbo spin echo