A stereological study of the mediodorsal thalamic nucleus in Down syndrome

- The mediodorsal thalamus was investigated in aged patients with Down syndrome (DS).
- Compared to controls, the DS brains had 40% fewer neurons.
- First stereological evidence for a reduction of cell numbers in the MDT nucleus in DS.
- The reduced neuron number was not followed by glial cell loss of the same magnitude.

The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69 years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small neurons, oligodendrocytes, and astrocytes) were estimated using the optical fractionator technique. The DS brains had an average of 3.41 × 106 total neurons in the MDT nucleus in contrast to 5.97 × 106 in the controls, with no overlap (2p = 0.004), affecting large (projecting) and small (local inhibitory) neurons nearly equally. In contrast, we observed no significant differences in either glial cell population. The cortical structures of the same four DS brains were previously estimated to be half the normal size of controls with a reduction in cell numbers whereas the basal ganglia were unaffected. As DS brains are affected by developmental delay, premature aging, and Alzheimer-like pathology, the finite cause of the reduced number of cells in MDT nucleus cannot be determined; however, these findings provide stereological evidence for a local reduction in neuron numbers in the MDT nucleus, which could affect the cognitive capacity of patients with DS.