Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression

Szapacs, Matthew; Mathews, Tiffany A.; Tessarollo, Lino; Lyons, W. Ernest; Mamounas, Laura A.; Andrews, Anne M.

doi:10.1016/j.jneumeth.2004.03.026

Cited by 130 publications

(87 citation statements)

References 70 publications

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“…However, our results differ somewhat from other studies that found reduced BDNF signaling in the ventral hippocampus and prefrontal cortex of SERT deficient rats [34,35]. Finally, another study of BDNF conducted in SERT +/+ , SERT +/-and SERT -/-mice did not yield any significant differences in BDNF protein levels between genotypes in hippocampus, frontal cortex, and brain stem [36]. In line with this report, we also did not detect altered BDNF levels in the prefrontal cortex of the SERT -/-mouse strain used in our study.…”

Section: Discussioncontrasting

confidence: 99%

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Kronenberg

Mosienko

Gertz

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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The interplay between BDNF signaling and the serotonergic system remains incompletely understood. Using a highly sensitive enzyme-linked immunosorbent assay, we studied BDNF concentrations in hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 -/-) mice lacking brain serotonin and serotonin transporter (SERT) deficient (SERT -/-) mice lacking serotonin re-uptake. Surprisingly, hippocampal BDNF was significantly elevated in Tph2 -/-mice, whereas no significant changes were observed in SERT -/-mice. Furthermore, BDNF levels were increased in the prefrontal cortex of Tph2 -/-but not of SERT -/-mice. Our results emphasize the interaction between serotonin signaling and BDNF. Complete lack of brain serotonin induces BDNF expression.

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Section: Discussioncontrasting

confidence: 99%

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Kronenberg

Mosienko

Gertz

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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“…Whole HYP and unilateral PFC and HPC from each mouse were homogenized by sonication in 3-4 ml of lysis buffer (100 mM PIPES (pH 7), 500 mM NaCl, 0.2% Triton X-100, 2 mM EDTA, 200 μM PMSF, and protease inhibitor cocktail (Sigma-Aldrich), followed by centrifugation for 30 min at 16 000 g at 4°C as previously described (Szapacs et al, 2004). Supernatants were then collected and 200 μl aliquots were removed to assess total protein concentration using the BCA Protein Assay Kit (Pierce).…”

Section: Bdnf Enzyme-linked Immune Assaymentioning

confidence: 99%

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

Maynard

Hill

Calcaterra

et al. 2015

Neuropsychopharmacol

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105

150

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Brain-derived neurotrophic factor (BDNF) regulates diverse biological functions ranging from neuronal survival and differentiation during development to synaptic plasticity and cognitive behavior in the adult. BDNF disruption in both rodents and humans is associated with neurobehavioral alterations and psychiatric disorders. A unique feature of Bdnf transcription is regulation by nine individual promoters, which drive expression of variants that encode an identical protein. It is hypothesized that this unique genomic structure may provide flexibility that allows different factors to regulate BDNF signaling in distinct cell types and circuits. This has led to the suggestion that isoforms may regulate specific BDNF-dependent functions; however, little scientific support for this idea exists. We generated four novel mutant mouse lines in which BDNF production from one of the four major promoters (I, II, IV, or VI) is selectively disrupted (Bdnf-e1, -e2, -e4, and -e6 mice) and used a comprehensive comparator approach to determine whether different Bdnf transcripts are associated with specific BDNF-dependent molecular, cellular, and behavioral phenotypes. Bdnf-e1 and -e2 mutant males displayed heightened aggression accompanied by convergent expression changes in specific genes associated with serotonin signaling. In contrast, BDNF-e4 and -e6 mutants were not aggressive but displayed impairments associated with GABAergic gene expression. Moreover, quantifications of BDNF protein in the hypothalamus, prefrontal cortex, and hippocampus revealed that individual Bdnf transcripts make differential, regionspecific contributions to total BDNF levels. The results highlight the biological significance of alternative Bdnf transcripts and provide evidence that individual isoforms serve distinct molecular and behavioral functions.

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“…Infusion of BDNF into the brain enhances the expression of tryptophan hydroxylase (TpOH) (the ratelimiting enzyme in 5HT synthesis), upregulates 5-HT uptake and its activity-dependent release, and even modifies the firing patterns of serotonergic neurons in the raphe (Siuciak et al, , 1998Celada et al, 1996;Zhou et al, 2000;Goggi et al, 2002). In BDNF heterozygous mutant ( + /À) mice, levels of forebrain 5-HT, fiber densities of forebrain 5-HT neurons, as well as the 5-HT clearance rate, were significantly impaired (Lyons et al, 1999;Szapacs et al, 2004;Daws et al, 2007). The functions of the 5-HT1 A and 5-HT2 A receptors also appear to be impaired in a mutant line in which the BDNF gene is deleted later in development Hensler et al, 2007).…”

Section: Bdnf Regulation Of 5-ht Neuron Development and Functionsmentioning

confidence: 99%

“…Not all results are consistent with this idea. For example, in SERT knockout mice which lack the 5-HTT, and thus have elevated levels of extracellular 5-HT, upregulation of BDNF could not be observed (Szapacs et al, 2004).…”

Section: -Ht Regulation Of Bdnf Gene Expression and Signalingmentioning

confidence: 99%

Interaction between BDNF and Serotonin: Role in Mood Disorders

Martinowich

2007

Neuropsychopharmacol

686

458

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Brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) are two seemingly distinct signaling systems that play regulatory roles in many neuronal functions including survival, neurogenesis, and synaptic plasticity. A common feature of the two systems is their ability to regulate the development and plasticity of neural circuits involved in mood disorders such as depression and anxiety. BDNF promotes the survival and differentiation of 5-HT neurons. Conversely, administration of antidepressant selective serotonin reuptake inhibitors (SSRIs) enhances BDNF gene expression. There is also evidence for synergism between the two systems in affective behaviors and genetic epitasis between BDNF and the serotonin transporter genes.

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Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression

Cited by 130 publications

References 70 publications

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

Interaction between BDNF and Serotonin: Role in Mood Disorders

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