Differential expression of TrkB isoforms switches climbing fiber-Purkinje cell synaptogenesis to selective synapse elimination.

Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood.

Phosphorylation and transcriptional activity regulation of retinoid-related orphan receptor alpha 1 by protein kinases C.

Retinoid-related orphan receptor alpha1 (RORalpha1) is a member of the nuclear receptor superfamily. It is highly expressed in CNS particularly in the cerebellum. Absence of this transcription factor in mice leads to several abnormalities, such as cerebellar atrophy linked to Purkinje cell death and impaired differentiation.

Cerebellar purkinje cell loss in heterozygous rora+/- mice: a longitudinal study.

The staggerer (sg) mutation is a spontaneous deletion in the Rora gene that prevents the translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. The homozygous Rorasg/sg mutant mouse, whose most obvious phenotype is ataxia associated with cerebellar degeneration, also displays a variety of other phenotypes. The heterozygous Rora+/sg is able to develop a cerebellum that is qualitatively normal but which suffers a significant loss of cerebellar neuronal cells with advancing age.

Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis.

Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a transcription factor belonging to the superfamily of nuclear receptors. Disruption of the Rora gene in the mouse results in a defect in the development of Purkinje cells leading to a cerebellar atrophy, which suggests a neuroprotective role for RORalpha. To test this hypothesis, the survival rate of lentiviral-mediated human RORalpha1-overexpressing neurones has been evaluated in response to different stressors disturbing the redox homeostasis, such as beta-amyloid peptide, c(2)-ceramide and H(2)O(2).