Fig. 2: TP53INP1 deficiency aggravates motor deficits and loss of nigral TH-positive neurons induced by AAV-mediated α-synuclein overexpression.

A, B Assessment of motor performance using the open field test for the spontaneous locomotor activity (A) and the cylinder test for the parkinsonian-like akinesia (B) in WT and Trp53inp1^−/− (KO) control mice and mice with unilateral intranigral injection of AAV2-CBA-human-α-synuclein at 15, 30, and 45 dpi. The injection leads to progressive deficits for the two genotypes, which were significantly worsened in Trp53inp1^−/− mice for locomotor performance in the open field. C Illustrative images of dually immunostained sections showing the time course of human α-synuclein expression and of TH neuron loss in the substantia nigra of WT mice. Note that human α-synuclein detection is limited to the injected side and associated with a progressive reduction in the numbers of labeled TH neurons, while no apparent loss is observed in the contralateral side. D Total numbers of TH⁺ neurons in the anterior and posterior subdivisions of the ipsilateral SNc measured in WT and KO mice at 15, 30, and 45 dpi and expressed as % of control. The progressive loss of these neurons both in the anterior and the posterior subdivisions of the injected SN was aggravated in KO mice. E Lack of changes in the numbers of TH+ neurons in the overall contralateral SNc at the time points examined in WT and KO mice expressed as a percent of control. In all graphs, data are means ± SEM of 6 mice per group, and the results of the two-way ANOVA are indicated within each graph. Only significant interaction is symbolized.