BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae

Chiaruttini, Cristina; Sonego, Maura; Baj, Gabriele; Simonato, Michele; Tongiorgi, Enrico

doi:10.1016/j.mcn.2007.08.011

Cited by 144 publications

(139 citation statements)

References 37 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…The behavior of full-length constructs was identical to that observed at both DIV7 and DIV18 (Fig. S1E) for the endogenous BDNF mRNAs analyzed using transcript-specific probes used previously in cortex (15) and hippocampus (14). Indeed, endogenous BDNF transcripts with exon 1, 2, 4, or 6 were located in the soma and proximal dendrites in unstimulated cultures, and KCl depolarization for 3 h induced targeting in distal dendrites of only exons 2 and 6 or total BDNF (Fig.…”

Section: Bdnf Transcripts and Proteinsupporting

confidence: 72%

“…We found that exons 2 and 6 localized into distal dendrites following 3 h of status epilepticus, whereas exons 1 and 4 were restricted to the soma even after this strong neuronal activation (14,15). On this basis, we proposed a hypothesis, the "spatial code hypothesis of BDNF transcripts," in which different BDNF splice variants, through the spatial segregation of their mRNA, represent a code to direct the protein to either the soma or proximal or distal dendrites (14,16).…”

mentioning

confidence: 94%

See 1 more Smart Citation

Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments

Baj

Leone²,

Chao³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

173

219

View full text Add to dashboard Cite

BDNF is produced from many transcripts that display distinct subcellular localization, suggesting that spatially restricted effects occur as a function of genetic and physiological regulation. Different BDNF 5′ splice variants give a restricted localization in the cell body or the proximal and distal compartments of dendrites; however, the functional consequences are not known. Silencing individual endogenous transcripts or overexpressing BDNF-GFP transcripts in cultured neurons demonstrated that whereas some transcripts (1 and 4) selectively affected proximal dendrites, others (2C and 6) affected distal dendrites. Moreover, segregation of BDNF transcripts resulted in a highly selective activation of the BDNF TrkB receptor. These studies indicate that spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments.development | neurotrophins | plasticity

show abstract

Section: Bdnf Transcripts and Proteinsupporting

confidence: 72%

mentioning

confidence: 94%

Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments

Baj

Leone²,

Chao³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

173

219

View full text Add to dashboard Cite

show abstract

“…Although exons I and IV transcripts display a somatic localization, exon VI (as well as exon II) can also be found in dendrites (Chiaruttini et al, 2008;Pattabiraman et al, 2005). On the basis of our data, it can be inferred that the somatic BDNF pool can be enhanced by stress despite ongoing antidepressant treatment.…”

Section: Stress-dependent Bdnf Modulation After Duloxetine R Molteni mentioning

confidence: 55%

Acute Stress Responsiveness of the Neurotrophin BDNF in the Rat Hippocampus is Modulated by Chronic Treatment with the Antidepressant Duloxetine

Molteni

Calabrese

Cattaneo

et al. 2008

Neuropsychopharmacol

112

View full text Add to dashboard Cite

Compelling evidence suggests that mood disorders are characterized by reduced neuronal plasticity that might be normalized by pharmacological intervention. Our study aimed to establish whether chronic antidepressant treatment could alter the modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) under a stressful condition. Therefore, adult male Sprague-Dawley rats were treated for 21 days with vehicle or with the SNRI duloxetine and, 24 h after the last injection, exposed to an acute swim stress (5 min) before being killed 15 min later. We found that chronic duloxetine treatment was able to modulate the rapid transcriptional changes of BDNF isoforms produced by an acute swim stress. Indeed whereas the mRNA levels of BDNF exon IV were upregulated by stress in vehicle as well as in duloxetine-treated rats, a significant increase of exon VI and exon IX was only found in rats that were pretreated with the antidepressant. These differential effects are in part because of selective changes in signaling pathways involved in the control of BDNF transcription. Moreover, the acute stressful episode significantly increased the levels of mature BDNF protein in the synaptosomal compartment in rats that were pretreated with the antidepressant, but not in control animals. Our results suggest that chronic antidepressant treatment might affect the responsiveness of BDNF under stressful conditions, suggesting that pharmacological intervention could 'prime' neuroprotective pathways and render them more responsive to preserve cell function and viability.

show abstract

“…In recent studies, we have demonstrated that BDNF transcripts differ in their subcellular localization (7). Exon 1 and 4 transcripts are localized in the cell soma, while exon 2 and 6 transcripts show a somato-dendritic localization.…”

mentioning

confidence: 95%

Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation

Chiaruttini

Vicario

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

200

229

View full text Add to dashboard Cite

Alternatively spliced brain-derived neurotrophic factor (BDNF) transcripts are targeted to distinct cellular compartments in neurons but the mechanisms underlying this sorting are unknown. Although only some BDNF isoforms are targeted to dendrites, we have found that the coding region common to all BDNF transcripts contains a constitutively active dendritic targeting signal and that this signal is suppressed in transcripts containing exons 1 or 4, which are restricted to the cell soma and proximal dendrites. This dendritic targeting signal is mediated by translin, an RNA-binding protein implicated in RNA trafficking, and is disrupted by the G196A mutation associated with memory deficits and psychiatric disorders. Molecular modeling and mutational studies indicate that the G196A mutation blocks dendritic targeting of BDNF mRNA by disrupting its interaction with translin. These findings implicate abnormal dendritic trafficking of BDNF mRNA in the pathophysiology of neuropsychiatric disorders linked to the G196A mutation.neuropsychiatric disorders ͉ neurotrophins S everal lines of evidence indicate that targeting of BDNF mRNA to dendrites plays a key role in mediating synaptic plasticity (1-4). However, the molecular mechanisms regulating this process and the differential subcellular localization of alternatively spliced BDNF transcripts, remain to be clarified.Multiple BDNF transcripts are generated by alternative splicing of one 5Ј exon with a shared 3Ј exon containing the entire BDNF coding region and either a short or long 3Ј UTR sequence (5, 6). In recent studies, we have demonstrated that BDNF transcripts differ in their subcellular localization (7). Exon 1 and 4 transcripts are localized in the cell soma, while exon 2 and 6 transcripts show a somato-dendritic localization. Thus, splice variants appear to encode spatial localization signals used to preferentially regulate BDNF expression in different subcellular domains (2, 3). A recent study has suggested that the long 3Ј UTR contains signals necessary for dendritic targeting of BDNF transcripts (4). However, it is unlikely that this mechanism can fully account for the differential dendritic targeting displayed by BDNF transcripts because more than one-third of exon 4 transcripts, which are retained in the soma, contain the long 3Ј UTR. Conversely, more than one-half of exon 6 transcripts, an isoform that displays targeting to dendrites, contain the short 3Ј UTR. To help define the mechanisms underlying differential localization of BDNF transcripts, we have tested the hypothesis that additional signals might be encoded by other BDNF mRNA regions.

show abstract

BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae

Cited by 144 publications

References 37 publications

Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments

Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments

Acute Stress Responsiveness of the Neurotrophin BDNF in the Rat Hippocampus is Modulated by Chronic Treatment with the Antidepressant Duloxetine

Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation

Contact Info

Product

Resources

About