Fig. 3
From: Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson’s disease
Full and selective protection of SN dopaminergic neurons in Cav2.3 knockout mice in a Parkinson’s disease mouse model. a Left: Tyrosine hydroxylase (TH) immunostaining of coronal midbrain sections of Cav2.3 wildtype and Cav2.3 knockout mice, repeatedly treated with MPTP/probenecid or saline as controls, as indicated. Middle: Stereological quantification of SN dopaminergic and VTA dopaminergic neurons (Cav2.3 wildtype saline: n = 9; Cav2.3 wildtype MPTP: n = 13; Cav2.3 knockout saline: n = 9; Cav2.3 knockout MPTP: n = 10), and relative remaining neurons in MPTP-treated mice. Right: Mean absolute counted numbers of SN dopaminergic neurons in all analyzed sections for all animals, section position according to bregma. Error bars: SEM. b Middle: Automated counting of all SN neurons (Cav2.3 wildtype saline: n = 9; Cav2.3 wildtype MPTP: n = 12; Cav2.3 knockout saline: n = 9; Cav2.3 knockout MPTP: n = 10), and relative remaining neurons in MPTP-treated mice. Right: Mean numbers of all SN neurons determined by automated neuron counts for all sections for all animals, section position according to bregma. Error bars: SEM. c Left: TH immunostaining of striatal sections of Cav2.3 wildtype and Cav2.3 knockout mice, repeatedly treated with MPTP/probenecid or saline as controls, as indicated. Middle: Optical density quantification of TH signal in dorsal striatum (DS) and ventral striatum (VS) (Cav2.3 wildtype saline: n = 9; Cav2.3 wildtype MPTP: n = 13; Cav2.3 knockout saline: n = 9; Cav2.3 knockout MPTP: n = 12), and relative remaining TH signal in MPTP-treated mice. Right: Mean intensities for all analyzed sections for all animals, section position according to bregma. Error bars: SEM. d Left: Striatal injection site documentation of an in vivo retrogradely traced adult mouse, aligned with the mouse brain atlas, and a labeled SN dopaminergic neuron, before UV-laser microdissection in fluorescent and brightfield mode. Scale bars: 10 µm. Middle: Cell-specific relative mRNA levels of Cav1.2 (wildtype: n = 8; knockout: n = 7), Cav1.3 (wildtype: n = 16; knockout: n = 17) and Cav3.1 (wildtype: n = 10; knockout: n = 10) in single SN dopaminergic neurons from adult Cav2.3 wildtype and Cav2.3 knockout mice. Right: Cell-specific relative mRNA levels of NCS-1 in single SN dopaminergic neurons from juvenile (wildtype: n = 10; knockout: n = 10) and adult (wildtype: n = 10; knockout: n = 10) Cav2.3 wildtype and Cav2.3 knockout mice. Data are given relative to the respective controls. Tukey's boxplots are shown. Significances are indicated by asterisks: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Data values and additional bootstrapping analysis are detailed in Supplementary Tables 8A/B, 4B/C and Supplementary Figs. 4/5. Source data are available as a Source Data file
