A two-step hybridization/subtraction procedure was employed to isolate markers for the later stages of Purkinje cell differentiation. From this screen, a novel Shaw potassium channel cDNA (Kv3.3b) was identified that is developmentally regulated. Expression of this channel is highly enriched in the brain, particularly in the cerebellum, where its expression is confined to Purkinje cells and dee...

Neurotrophins regulate diverse aspects of neuronal development and plasticity, but their precise in vivo functions during neural circuit assembly in the central brain remain unclear. We show that the neurotrophin receptor tropomyosin-related kinase C (TrkC) is required for dendritic growth and branching of mouse cerebellar Purkinje cells. Sparse TrkC knockout reduced dendrite complexity, but gl...

Previous studies of wild-type mice or mutant-wild-type mouse chimeras using the neurological mutant staggerer have supported a numerical matching hypothesis for target-related cell death. However, analyses of chimeras of a second neurological mutant, lurcher, have suggested that there may be significant flexibility in the relationship between the numbers of pre- and postsynaptic neurons. Wherea...

In several regions of the developing nervous system, neurons undergo programmed cell death. In the rat cerebellum, Purkinje cell apoptosis is exacerbated when cerebellar slices are cultured during the first postnatal week. To understand the mechanism of this developmental apoptosis, we took advantage of its inhibition by the steroid analog mifepristone. This effect did not involve the classical...

We have investigated the expression of a unique class of neuropeptides, the cerebellins, in normal and neurodevelopmentally mutant mice. Employing HPLC separation, gas-phase Edman sequencing, and immunocytochemistry, the normal Balb/c mouse cerebellum is shown to contain 2 Purkinje cell-specific neuropeptides, cerebellin and des-Ser1-cerebellin. In this strain of mouse the cerebellins appear du...

Cardiac Purkinje cells are important triggers of ventricular arrhythmias associated with heritable and acquired syndromes; however, the mechanisms responsible for this proarrhythmic behavior are incompletely understood. Here, through transcriptional profiling of genetically labeled cardiomyocytes, we identified expression of Purkinje cell protein-4 (Pcp4), a putative regulator of calmodulin and...

The Purkinje cell degeneration (pcd) mouse undergoes retinal photoreceptor degeneration and Purkinje cell loss. Nna1 is postulated to be the causal gene for pcd. We show that a BAC containing the Nna1 gene rescues retinal photoreceptor loss and Purkinje cell degeneration, confirming that Nna1 loss-of-function is responsible for these phenotypes. Mutation of the zinc-binding domain within the tr...

Ibogaine, an indole alkaloid that causes hallucinations, tremor, and ataxia, produces cerebellar neurotoxicity in rats, manifested by degeneration of Purkinje cells aligned in narrow parasagittal bands that are coextensive with activated glial cells. Harmaline, a closely related alkaloid that excites inferior olivary neurons, causes the same pattern of Purkinje cell degeneration, providing a cl...

Background: Deltamethrin (DM) is a synthetic pyrethroid insecticide that can elicit neurotoxicity, and lead to apoptosis. There is accumulating evidence that oleuropein (OE) has anti-apoptotic effect. This study aimed at determining the DM toxicity and anti-apoptotic effect of OE pretreatment in cerebellar Purkinje neurons. Materials and Methods: Rats were randomly divided into four groups a...