Activation of pedunculopontine tegmental nucleus neurons improves gait behavior of rat models of Parkinson's disease: a study based on optogenetics method

Objective To investigate the mechanism of improvement of gait behavior in PD rat models by low frequency electrical stimulation of pedunculopontine tegmental nucleus (PPTN) by optogenetics method. Methods (1) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 1, a lesion group 1 and a photoactivation group (n=8); normal saline was injected into the right medial frontal tract (MFB) of the sham-operated group 1; 6-hydroxydopamine (6-OHDA) was injected into the lesion group 1 and photoactivation group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-ChR2-mcherry into the right PPTN of the three groups was performed, and the photoactivation group received blue-ray stimulation by implanting optical fibers into the PPTN at the same time. (2) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 2, a lesion group 2 and a photoinhibition group (n=8); normal saline was injected into right MFB of the sham-operated group 2; 6-OHDA was injected into the lesion group 2 and photoinhibition group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-NpHR-mcherry into the right PPTN of the three groups was performed, and the photoinhibition group received yellow-ray stimulation by implanting optical fibers into the PPTN at the same time. (3) Three weeks after injection of adeno-associated virus, Catwalk gait analysis was used to assess the behavioral ability of rats in each group. Results (1) As compared with the sham-operated group 1, lesion group 1 had significantly increased front claw spacing and back front claw spacing, and significantly decreased stride length and pressure of damaged lateral and contralateral limbs, and significantly decreased swing speed of contralateral limb (P 0.05). Conclusion The mechanism of low frequency electrical stimulation of PPTN improving gait behavior of PD rat models is related to activation of PPTN neurons. Key words: Parkinson's disease; Gait behavior; Deep brain stimulation; Pedunculopontine nucleus; Neuron; Optogenetics method