Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an abnormal expansion of CAG repeats in the Ataxin-1 (ATXN1) gene and characterized by motor deficits and cerebellar neurodegeneration. Even though mutant ATXN1 is expressed from an early age, disease onset usually occurs in patient's mid-thirties, indicating the presence of compensatory factors that limit the toxic effects of mutant ATXN1 early in disease. Brain derived neurotrophic factor (BDNF) is a growth factor known to be important for the survival and function of cerebellar neurons. Using gene expression analysis, we observed altered BDNF expression in the cerebella of Purkinje neuron specific transgenic mouse model of SCA1, ATXN1[82Q] mice, with increased expression during the early stage and decreased expression in the late stage of disease. We therefore investigated the potentially protective role of BDNF in early stage SCA1 through intraventricular delivery of BDNF via ALZET osmotic pumps. Extrinsic BDNF delivery delayed onset of motor deficits and Purkinje neuron pathology in ATXN1[82Q] mice supporting its use as a novel therapeutic for SCA1.
Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms
Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1)
Abnormal cerebellar development and foliation in BDNF-/- mice reveals a role for neurotrophins in CNS patterning
Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF
BDNF increases homotypic olivocerebellar reinnervation and associated fine motor and cognitive skill
Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Differential expression of TrkB isoforms switches climbing fiber-Purkinje cell synaptogenesis to selective synapse elimination
SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776
Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1.
Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to neuronal dysfunction in ATXN1[82Q] mice.
Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction.
Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1.
Dual actions of brain-derived neurotrophic factor on GABAergic transmission in cerebellar Purkinje neurons
Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum
Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7
Purkinje cell ataxin-1 modulates climbing fiber synaptic input in developing and adult mouse cerebellum
Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data
Systemic delivery of recombinant brain derived neurotrophic factor (BDNF) in the R6/2 mouse model of Huntington's disease
Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data
Decreased expression of glutamate transporter GLAST in bergmann glia is associated with the loss of Purkinje neurons in the spinocerebellar ataxia type 1
Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability
Cerebellar Transcriptome Profiles of ATXN1 Transgenic Mice Reveal SCA1 Disease Progression and Protection Pathways
Diminishing return for mechanistic therapeutics with neurodegenerative disease duration?: There may be a point in the course of a neurodegenerative condition where therapeutics targeting disease-causing mechanisms are futile
Inhibition of colony-stimulating factor 1 receptor early in disease ameliorates motor deficits in SCA1 mice
Motor and Cerebellar Architectural Abnormalities during the Early Progression of Ataxia in a Mouse Model of SCA1 and How Early Prevention Leads to a Better Outcome Later in Life
High-throughput screening against protein:protein interaction interfaces reveals anti-cancer therapeutics as potent modulators of the voltage-gated Na+ channel complex
Going Too Far Is the Same as Falling Short† : Kinesin-3 Family Members in Hereditary Spastic Paraplegia
Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model.
Post-symptomatic Delivery of Brain-Derived Neurotrophic Factor (BDNF) Ameliorates Spinocerebellar Ataxia Type 1 (SCA1) Pathogenesis.
Role of Nuclear Factor Kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach.
Developmental Alterations in Adult-Onset Neurodegenerative Disorders: Lessons from Polyglutamine Diseases.
Brain Injury & Trauma
brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.