Fig 1.
Ganglioside biosynthetic pathways.
The main gangliosides found in brain are a-series and b-series gangliosides (encircled). Gangliosides are synthesized by sequential addition of sugars and sialic acid residues onto a sphingosine backbone through the action of various glycosyltransferases (ex., St3gal5, B4galnt1, B3galt4, St8sia1) and sialyltransferases (St3gal2, St8sia5).
Table 1.
Subject characteristics.
Fig 2.
B3GALT4 gene expression is lower in residual neuromelanin-containing cells in the PD SN than in control SN neurons.
A. In situ hybridization for B3GALT4 gene expression in control (N) and PD substantia nigra (SN). Using the RNAscope 2.5 HD Detection Kit-Red (ACB Bio), each red dot represents a single RNA molecule. Scale = 25 μm. B. Counts of the number of dots (RNA molecules) per neuron showed significantly less B3GALT4 RNA in cells in the PD SN (196 cells analyzed) compared to the control SN (269 cells analyzed). ***P = 0.0001 compared to Normal. Neuromelanin appears as brown/black aggregates in cells.
Fig 3.
ST3GAL2 gene expression is lower in residual neuromelanin-containing cells in the PD SN than in control SN neurons.
A. In situ hybridization for ST3GAL2 gene expression in control (N) and PD substantia nigra (SN). Using the RNAscope 2.5 HD Detection Kit-Red (ACB Bio), each red dot represents a single RNA molecule. Scale = 25 μm. B. Counts of the number of dots (RNA molecules) per neuron showed significantly less ST3GAL2 RNA in cells in the PD SN (218 cells analyzed) compared to the control SN (146 cells analyzed). ***P < 0.0001 compared to Normal. Neuromelanin appears as brown/black aggregates in cells.
Fig 4.
Graphs showing the distribution B3GALT4 (a) and ST3GAL2 (B) gene expression per neuromelanin-containing neuron in normal and PD substantia nigra (SN).
Each dot represents the number of RNA molecules (red dots counted per cell) counted in each cell sampled. For both genes, there is overlap in the extent to which these genes are expressed in normal and PD SN neurons.
Fig 5.
Within a section, some cells located outside of the substantia nigra (SN) showed much higher ST3GAL2 and B3GALT4 gene expression levels than neuromelanin-containing cells located in the SN in the PD brain.
A. ST3GAL2 gene expression was relatively low in neuromelanin-containing cells in the PD SN (as indicated by the low number of red dots in cells containing brown/black aggregates indicative of neuromelanin) compared to the level of ST3GAL2 gene expression that could be observed in neurons in the same section located outside of the SN (B). Similarly, B3GALT4 gene expression was relatively low in neuromelanin-containing cells in the PD SN (C, as indicated by the low number of red dots in cells containing brown/black aggregates indicative of neuromelanin) compared to the level of B3GALT4 gene expression that could be observed in neurons in the same section located outside of the SN (D). Scale = 25 μm for each.