BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons

Caldeira, Margarida V.; Melo, Carlos; Pereira, Daniela; Carvalho, Rita F.; Carvalho, Ana Luı́sa; Duarte, Carlos B.

doi:10.1016/j.mcn.2007.02.019

Cited by 215 publications

(141 citation statements)

References 80 publications

Supporting

Mentioning

136

Contrasting

Order By: Relevance

“…In addition to the proteins identified in the proteomics analysis discussed above, target oriented studies have shown effects of BDNF in total expression of AMPA and NMDA receptor subunits in cultured hippocampal and cortical neurons (Caldeira et al, 2007a(Caldeira et al, , 2007bFortin et al, 2012;Guire et al, 2008;Narisawa-Saito et al, 1999;Small et al, 1998). Interestingly, stimulation of hippocampal neurons with BDNF also increased the synaptic accumulation of GluA1 AMPA receptor subunit, by a mechanism dependent on mTOR and Ca 2þ -and calmodulin-dependent protein kinase kinase (CaMKK) (Caldeira et al, 2007a;Fortin et al, 2012;Guire et al, 2008).…”

Section: Bdnf-induced Changes In the Neuronal Proteomementioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

Self Cite

View full text Add to dashboard Cite

a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

show abstract

Section: Bdnf-induced Changes In the Neuronal Proteomementioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been previously shown that cholesterol reduction triggers TrkB activation (Martin et al, 2008), and TrkB signaling has been linked to enhanced NMDAR transcription (Caldeira et al, 2007). Therefore, we tested whether cholesterol removal from hippocampal slices would alter NMDAR mRNA levels.…”

Section: Synaptic Potentiation Of Nmdars By Cholesterol Removal Requimentioning

confidence: 99%

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Brachet¹,

Norwood²,

Brouwers³

et al. 2015

J Gen Physiol

View full text Add to dashboard Cite

“…Differential Detergent Solubilization, SDS-PAGE and Immunoblotting-Protein extracts were prepared according to a modified version of a previously described protocol (35). Briefly, cortical neurons were washed twice with ice-cold PBS and once more with PBS supplemented with a mixture of protease inhibitors (0.1 mM PMSF, 1 g/ml leupeptin, 1 g/ml aprotitin).…”

Section: Methodsmentioning

confidence: 99%

Activity and Protein Kinase C Regulate Synaptic Accumulation of N-Methyl-d-aspartate (NMDA) Receptors Independently of GluN1 Splice Variant

Ferreira

Rooyakkers

She

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

NMDA receptors are calcium-permeable ionotropic receptors that detect coincident glutamate binding and membrane depolarization and are essential for many forms of synaptic plasticity in the mammalian brain. The obligatory GluN1 subunit of NMDA receptors is alternatively spliced at multiple sites, generating forms that vary in N-terminal N1 and C-terminal C1, C2, and C2 cassettes. Based on expression of GluN1 constructs in heterologous cells and in wild type neurons, the prevalent view is that the C-terminal cassettes regulate synaptic accumulation and its modulation by homeostatic activity blockade and by protein kinase C (PKC). Here, we tested the role of GluN1 splicing in regulated synaptic accumulation of NMDA receptors by lentiviral expression of individual GluN1 splice variants in hippocampal neurons cultured from GluN1 (؊/؊) mice. High efficiency transduction of GluN1 at levels similar to endogenous was achieved. Under control conditions, the C2 cassette mediated enhanced synaptic accumulation relative to the alternate C2 cassette, whereas the presence or absence of N1 or C1 had no effect. Surprisingly all GluN1 splice variants showed >2-fold increased synaptic accumulation with chronic blockade of NMDA receptor activity. Furthermore, in this neuronal rescue system, all GluN1 splice variants were equally rapidly dispersed upon activation of PKC. These results indicate that the major mechanisms mediating homeostatic synaptic accumulation and PKC dispersal of NMDA receptors occur independently of GluN1 splice isoform. N-Methyl-D-aspartate (NMDA)3 type ionotropic glutamate receptors are present at excitatory synapses in the nervous system. These receptors play roles in neuronal development, learning and memory and neurological diseases (1-4). They require the simultaneous binding of glutamate and membrane depolarization for the channel to open, which makes them coincidence detectors of pre-and postsynaptic activity. Calcium flux through NMDA receptors triggers signal transduction cascades that are necessary for inducing many forms of synaptic plasticity. NMDA receptors are heteromeric cation channels composed of GluN1 and GluN2 subunits, and more rarely GluN3 subunits (5). The obligatory GluN1 subunit, which binds the co-agonist glycine, is encoded by a single gene which gives rise to eight GluN1 variants through alternative splicing of exons 5, 21, and 22 (6). The expression of GluN1 splice variants changes during development and across brain regions (7,8), and can be regulated by neuronal activity (9, 10). Therefore, the composition of NMDA receptor signaling complexes may be dynamically regulated through the splicing of GluN1.At the region encoding the N-terminal domain of GluN1, alternative splicing of exon 5 gives rise to splice variants containing or lacking the N1 cassette which regulates receptor deactivation kinetics as well as sensitivity to pH, Zn 2ϩ , and spermine (11-13). Alternative splicing of exons 21 and 22 generates four different splice variants at the intracellular C terminus of GluN1, var...

show abstract

BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons

Cited by 215 publications

References 80 publications

BDNF-induced local protein synthesis and synaptic plasticity

BDNF-induced local protein synthesis and synaptic plasticity

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Activity and Protein Kinase C Regulate Synaptic Accumulation of N-Methyl-d-aspartate (NMDA) Receptors Independently of GluN1 Splice Variant

Contact Info

Product

Resources

About