Molecular and cellular neurosciences
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Mol. Cell. Neurosci. · Feb 2012
Transcript expression levels of full-length alpha-synuclein and its three alternatively spliced variants in Parkinson's disease brain regions and in a transgenic mouse model of alpha-synuclein overexpression.
Alternative splicing is a complex post-transcriptional process that can be regulated by cis-acting elements located within genomic non-coding regions. Recent studies have identified that polymorphic variations in non-coding regions of the α-synuclein gene (SNCA) locus are associated with an increased risk for developing Parkinson's disease (PD). The underlying mechanism(s) for this susceptibility may involve changes in α-synuclein mRNA expression and alternative splicing. ⋯ While most transcripts were elevated in ASO mice when compared to WT mice, the most prominent increase was found in the ventral midbrain of 15-month-old ASO mice. These results demonstrate region-specific human α-synuclein transcript level abnormalities in PD patients and in a transgenic mouse model of α-synucleinopathy. This study is relevant to understanding the normal, adaptive, or pathological role(s) of α-synuclein splice variants.
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Mol. Cell. Neurosci. · Feb 2012
Stimulation of α(2A)-adrenoceptors promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex.
Dendritic spines are tiny protrusions along dendrites that receive excitatory synaptic inputs and compartmentalize postsynaptic responses in the mature brain. It is known that change in spine morphology is associated with brain functions such as learning and memory. α(2A)-Adrenoceptors (α(2A)-ARs) are highly expressed in cortical neurons and play important roles in neuronal differentiation, growth and neurotrophy. However, little is known about the role of α(2A)-ARs in the maturation of dendritic spines. ⋯ In parallel, the expression of PSD95 (a postsynaptic protein) in guanfacine-treated neurons was enhanced, while that of synapsin (a pre-synaptic protein) kept unchanged. These effects of guanfacine were blocked by co-administered yohimbine, a non-selective α(2)-AR antagonist. The present results implicate a prominent role of α(2A)-ARs in regulating the maturation of dendritic spines in the mPFC.