Distinct subcellular localization of BDNF transcripts in cultured hypothalamic neurons and modification by neuronal activation

Aliaga, Esteban; Mendoza, Isabel; Tapia‐Arancibia, Lucía

doi:10.1007/s00702-008-0159-8

Cited by 29 publications

(19 citation statements)

References 50 publications

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“…A similar segregation of BDNF mRNA variants has also been observed in hypothalamic (25) and cortical neurons (15), suggesting that our model can be applied to several neuronal types. A slight discrepancy in the actual distances or RDF values between this and our previous studies (15,17) does not affect the general conclusions on the differential localization of BDNF transcripts, and is accounted for by different culture conditions and by the fact that only apical dendrites were measured here, whereas previous studies also included basal dendrites, which are generally shorter and tend to have a higher RDF.…”

Section: Discussionsupporting

confidence: 75%

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.

179

219

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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

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Section: Discussionsupporting

confidence: 75%

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.

179

219

View full text Add to dashboard Cite

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“…For instance, the mood stabilizers lithium and valproate selectively activate promoter 6 of BDNF (Yasuda et al, 2009), while chronic duloxetine treatment induces enhanced mRNA levels for exons 1 and 4; however, the expression of exon 6 was reduced in the cortex (Calabrese et al, 2007). In our study, the treatments considered caused an increase in BDNF transcription and a specific translocation in CA3 distal dendrites of the exon 6 BDNF mRNA isoform, while in the case of exon 4, which was previously found in the soma and proximal dendrites (Aliaga et al, 2009;Baj et al, 2011), we found proximal or no dendritic staining and a decrease in CA3 following RBX treatment. Hence, these results are further evidence that enhanced BDNF mRNA translocation in distal dendrites is not a direct consequence of increased global transcription (Tongiorgi, 2008).…”

Section: Discussionsupporting

confidence: 45%

Physical Exercise and Antidepressants Enhance BDNF Targeting in Hippocampal CA3 Dendrites: Further Evidence of a Spatial Code for BDNF Splice Variants

Baj

D’Alessandro

Musazzi

et al. 2012

Neuropsychopharmacol

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Brain-derived neurotrophic factor (BDNF) is encoded by multiple BDNF transcripts, whose function is unclear. We recently showed that a subset of BDNF transcripts can traffic into distal dendrites in response to electrical activity, while others are segregated into the somatoproximal domains. Physical exercise and antidepressant treatments exert their beneficial effects through upregulation of BDNF, which is required to support survival and differentiation of newborn dentate gyrus (DG) neurons. While these DG processes are required for the antidepressant effect, a role for CA1 in antidepressant action has been excluded, and the effect on CA3 neurons remains unclear. Here, we show for the first time that physical exercise and antidepressants induce local increase of BDNF in CA3. Voluntary physical exercise for 28 consecutive days, or 2-week treatment with 10 mg/kg per day fluoxetine or reboxetine, produced a global increase of BDNF mRNA and protein in the neuronal somata of the whole hippocampus and a specific increase of BDNF in dendrites of CA3 neurons. This increase was accounted for by BDNF exon 6 variant. In cultured hippocampal neurons, application of serotonin or norepinephrine (10-50 mM) induced increase in synaptic transmission and targeting of BDNF mRNA in dendrites. The increased expression of BDNF in CA3 dendrites following antidepressants or exercise further supports the neurotrophin hypothesis of antidepressants action and confirms that the differential subcellular localization of BDNF mRNA splice variants provides a spatial code for a selective expression of BDNF in specific subcellular districts. This selective expression may be exploited to design more specific antidepressants.

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“…The studies mentioned above quantified total BDNF expression. However, transcripts initiating from exons I, II and III are expressed predominantly in neurons whereas transcripts initiating from exons IV, V and VI are expressed by both neurons and astrocytes within the naïve brain [69]. Normal expression of all transcripts may be necessary for wellness, as a knockout of even one of the 9 BDNF transcripts caused depressive-like behavior of mice [70].…”

Section: Discussionmentioning

confidence: 99%

Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

Park

Dantzer

Kelley

et al. 2011

J Neuroinflammation

133

115

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Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.

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Distinct subcellular localization of BDNF transcripts in cultured hypothalamic neurons and modification by neuronal activation

Cited by 29 publications

References 50 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

Physical Exercise and Antidepressants Enhance BDNF Targeting in Hippocampal CA3 Dendrites: Further Evidence of a Spatial Code for BDNF Splice Variants

Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

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