Density of cerebellar basket and stellate cells in autism: evidence for a late developmental loss of Purkinje cells.

Abstract

Alterations in the cerebellum have been described as a neuropathological feature of autism. Although numerous studies have focused on the Purkinje cell (PC), the projection neuron of the cerebellar cortex, PC function is critically dependent on their innervation by the GABAergic basket cells (BCs) and stellate cells (SCs) in the cerebellar molecular layer. The present study was designed to determine whether there are differences in the packing density of these inhibitory interneurons or whether the ratio of these interneurons to PCs differs in autistic and age-matched control brains. The GABAergic interneurons were identified by using immunohistochemistry for parvalbumin (PV) in serial sections from the posterior cerebellar lobe of six autistic and four control brains and counted using stereological principles. Prior PC counts in the same area on adjacent sections (Whitney et al., 2008) were available and were used to calculate the number of BCs and SCs per PC. In this sample of brains, no statistically significant difference was detected between the autistic and the control groups in the density of BCs or SCs (P = 0.44 and P = 0.84, respectively) or in the number of BCs or SCs per PC (P = 0.47 and P = 0.44, respectively). The preservation of BCs and SCs, in the presence of the reduced PC numbers as found in at least two, and possibly three, of these six autistic cases (Whitney et al., 2008) suggests that PCs were generated, migrated to their proper location in the PC layer, and subsequently died in the autistic cases that showed a reduction in PCs.