GAIT CHARACTERIZATION IN A MOUSE MODEL OF CHRONIC MILD STRESS- AND 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED NEUROINFLAMMATION

Serinelli FC¹, Kashyrina M², De Nuccio F², Panaro MA³, Cianciulli A³, Ruggiero M³, Porro C⁴, Ichas F⁵, Nicolardi N¹ and Lofrumento DD¹ | ¹Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy; ²Department of Experimental Medicine, University of Salento, Lecce, Italy; ³Department of Biosciences, Biotechnologies and Environment, University of Bari, Italy; ⁴Department of Clinical and Experimental Medicine, University of Foggia, Italy; ⁵Institut des Maladies Neurodégénératives, CNRS, Université de Bordeaux, France

Chronic mild stress (CMS) is an etiological risk factor for neuroinflammation that, in turn, is involved in the pathogenesis and progression of Parkinson’s disease (PD). To study the relationship between CMS, neuroinflammation and PD, we set up an in vivo model in which mice were subjected to CMS and, at the end of treatment, received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that causes the selective degeneration of the substantia nigra dopaminergic neurons, that is the main pathological feature of PD. In patients, disturbances in gait are symptomatic of PD. In mice, the administration of MPTP results in PD symptoms, including gait alteration. Several studies in mouse models of PD have characterized gait by estimating stride parameters by painting animals’ paws. Therefore, to compare the effects CMS and MPTP on mice gait, from the analysis footprint patterns four step parameters were measured: stride length, hind-base width, front-base width and overlap between forepaw and hindpaw placement. Control and stressed mice exhibited comparable stride lengths for both forepaws and hindpaws. By contrast, MPTP-treated mice displayed a significantly shorter stride length compared with control mice (p<0.05), as well as MPTP-treated stressed mice compared to the ones subjected only to CMS (p<0.05). The frontbase width did not differ significantly in mice from all experimental conditions; in contrast, the hindbase width of MPTP-treated mice was broader than that shown by controls (p<0.05); also hindbase width of MPTP-treated stressed mice resulted significantly higher compared to the one of mice subjected only to CMS (p<0.05). Stressed mice displayed reduced hindbase width compared to control one. The front/hind footprint overlap provides an indication of the accuracy of foot placement and of the uniformity of step alternation: surprisingly, MPTP-treated mice displayed a footprint overlap similar to control one whereas, as expected, overlap in MPTPtreated stressed mice resulted significantly lower compared to the ones subjected only to CMS (p<0.05). Although stressed mice displayed better step overlap compared to control one, the variability of the distances measured resulted higher. Overall, these data suggest that MPTP induced in both unstressed and stressed mice a significative gait alteration compared to respective controls, while the effects of CMS on motor behaviour were limited to the alteration of the uniformity of step alternation.