Abstract
Dendritic growth and branching are highly regulated processes and are essential for establishing proper neuronal connectivity. There is a critical phase of early dendrite development when these are heavily regulated by external cues such as trophic factors. Brain-derived neurotrophic factor (BDNF) is a major trophic factor known to enhance dendrite growth in cortical neurons, but the molecular underpinnings of this response are not completely understood. We have identified that BDNF induced translational regulation is an important mechanism governing dendrite development in cultured rat cortical neurons. We show that BDNF treatment for 1 h in young neurons leads to translational up-regulation of an important actin regulatory protein LIM domain kinase 1 (Limk1), increasing its level locally in the dendrites. Limk1 is a member of serine/threonine (Ser/Thr) family kinases downstream of the Rho-GTPase pathway. BDNF induced increase in Limk1 levels leads to increased phosphorylation of its target protein cofilin1. We observed that these changes are maintained for long durations of up to 48 h and are mediating increase in number of primary dendrites and total dendrite length. Thus, we show that BDNF induced protein synthesis leads to fine-tuning of the actin cytoskeletal reassembly and thereby mediate dendrite development.
Highlights
During neuronal development, dendritic growth and patterning lay down the basic architecture of the neuronal network
To measure the transcriptional contribution, we examined the total levels of LIM domain kinase 1 (Limk1) mRNA on Brain-derived neurotrophic factor (BDNF) treatment
We did not observe a significant increase in total Limk1 mRNA levels as quantitated by Quantitative PCRs (qPCRs). (Figure 1C)
Summary
Dendritic growth and patterning lay down the basic architecture of the neuronal network. In the early phase of perinatal development, the dendrite branches are highly dynamic and are affected significantly by different cues This dynamic phase of development is a critical time window which later is replaced with a stable phase where dendritic branches show minimal growth and pruning. A large number of studies have focussed on understanding spine formation, pruning and plasticity in mature dendrites, the molecular details governing early dendrite development is not completely understood. This understanding is imperative in the context of several neurodevelopmental disorders, as defects in this critical window lead to long term and irreversible changes in the neuronal connectivity
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