Experimental Parkinsonism induced by tetanus toxin injected into basal ganglia

Local inhibitory circuits and long-range inhibitory projections within the interconnected basal ganglia nuclei are critical for control of voluntary movement and pathophysiology of different extrapyramidal movement disorders. Herein, we examined the major motor effects of tetanus neurotoxin (TeNT), a presynaptic neurotoxin selectively targeting GABA-ergic synaptic transmission, injected into individual basal ganglia nuclei.

Rats were injected with low-dose TeNT unilaterally into globus pallidus internus (GPi, 0.4-ng TeNT), substantia nigra (SN, 0.4-ng TeNT) or caudate putamen (CPu, 0.1-, 0.4- and 0.8-ng TeNT). Effects of TeNT-induced disinhibition were characterized by repeated assessments of motor coordination, gait and rotational behaviour, followed by measurement of regional protein content of major neuronal monoaminergic, GABA-ergic and glutamatergic population markers.

Effects of TeNT injections into the GPi and CPu were more prominent and associated with decreased stride length and slower step cycle. CPu injections induced contralateral plantar misplacement during beamwalk transition. Rotational behaviour was evident as spontaneous ipsiversive circling during open field observation (augmented by D-amphetamine) and swimming. Along with gradual recovery of motor impairments over 2 weeks, the effects of TeNT were not associated with epileptogenesis or changed regional content of neuronal markers.

Tetanus toxin injected into the basal ganglia evokes transient hypokinetic motor dysfunctions, consistent with experimental Parkinsonism, with differential occurrence of individual motor symptoms depending on the region targeted. These results suggest that TeNT might be a useful non-neurodegenerative pharmacological agent for investigating motor control abnormalities involving GABA-ergic basal ganglia circuits.