Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant

Ivy, Autumn S; Rodriguez, F.; Garcia, Celithelma; Chen, M.J.; Russo-Neustadt, Amelia

doi:10.1016/s0091-3057(03)00044-3

Cited by 142 publications

(90 citation statements)

References 53 publications

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“…Recently, several lines of evidence suggest that a deficiency in neurotransmitters in the brain alter BDNF expression, leading to brain diseases, which indicates a complex modulatory relationship between BDNF and the serotonin system (Ivy et al, 2003;Palazidou, 2012;Pezet & Malcangio, 2004). BDNF can augment 5-HT signaling; in turn, 5-TH stimulates BDNF expression (Goggi et al, 2002;Juric et al, 2006;Mamounas et al, 2000;Mattson et al, 2004;Siuciak et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, an increasing number of studies have proven that the expression of the brain-derived nerve factor (BDNF) mRNA, particularly within the hippocampus, is regulated by stress and by therapeutic agents, such as antidepressants (Coppell et al, 2003;Lindvall et al, 1994;Molteni et al, 2006;Nibuya et al, 1995;Smith et al, 1995). Neurotransmitters have been implicated in the regulation of BDNF mRNA expression (Ivy et al, 2003;Juric et al, 2006;Lindholm et al, 1994;Palazidou et al, 2012;Thoenen et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression

Liang

Huang

Wang

et al. 2014

Pharmaceutical Biology

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Objective: This study compared the antidepressant ability of FAE with that of HG in mice and further investigated the antidepressant-like effects and potential mechanisms of HG in rats subjected to unpredictable chronic mild stress (UCMS). Materials and methods: Mice received FAE (50 mg/kg) and HG (20 mg/kg) once a day via intragastric administration (i.g.) for 3 weeks. The anxiolytic and antidepressant activities of FAE and HG were compared using elevated plus maze (EPM) and behavioral despair tests including tail suspension test (TST) and forced swimming test (FST), respectively. Antidepressant effects of HG (5 mg/kg) were assessed using the UCMS depressive rat model. Moreover, the levels of monoamine neurotransmitters and relevant gene expression in UCMS rats' hippocampi were determined through high-performance liquid chromatography with electrochemical detection and real-time polymerase chain reaction techniques. Results: The results of our preliminary screening test suggest that HG at 20 mg/kg, while not FAE at 50 mg/kg, significantly decreased the immobility in both TST and FST compared with the vehicle group when administered chronically; however, there were no significant differences observed between the HG and the FAE group. Chronic administration of HG failed to significantly reverse the altered crossing and rearing behavioral performance, time spent in the open arm and closed entries in the EPM, even if they showed an increased tendency, but HG significantly increased the percent of sucrose preference in the sucrose preference test (SPT) and decreased the immobility time in the FST. HG showed that significant increases of norepinephrine and serotonin levels and exhibited a tendency to increase the expression of 5-hydroxytryptamine (serotonin) 1A receptor mRNA, and to significantly decrease the expression of the mRNA for the serotonin transporter (5-HTT). However, there were no significant differences in the expression of the brain-derived neurotrophic factor. Conclusion: These findings confirm the antidepressant-like effects of HG in a behavioral despair test and UCMS rat model, which may be associated with monoamine neurotransmitters and 5-HTT mRNA expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression

Liang

Huang

Wang

et al. 2014

Pharmaceutical Biology

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“…S2). Antidepressants increase hippocampal BDNF expression through enhanced 5-HT or norepinephrine (NE) neurotransmission (15)(16)(17)(18). We reasoned that if NAS activates TrkB signaling indirectly by promoting BDNF secretion, scavenging BDNF should attenuate NAS-mediated activation of TrkB.…”

Section: Nas But Not Other Serotonin Metabolites Induces Trkb Activmentioning

confidence: 99%

N -acetylserotonin activates TrkB receptor in a circadian rhythm

Jang

Liu

Sompol

et al. 2010

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

172

166

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Brain-derived neurotrophic factor (BDNF) is a cognate ligand for the TrkB receptor. BDNF and serotonin often function in a cooperative manner to regulate neuronal plasticity, neurogenesis, and neuronal survival. Here we show that NAS (N-acetylserotonin) swiftly activates TrkB in a circadian manner and exhibits antidepressant effect in a TrkB-dependent manner. NAS, a precursor of melatonin, is acetylated from serotonin by AANAT (arylalkylamine Nacetyltransferase). NAS rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin-and MT3 receptor-independent manner. Administration of NAS activates TrkB in BDNF knockout mice. Furthermore, NAS, but not melatonin, displays a robust antidepressant-like behavioral effect in a TrkB-dependent way. Endogenous TrkB is activated in wild-type C3H/f +/+ mice but not in AANAT-mutated C57BL/ 6J mice, in a circadian rhythm; TrkB activation is high at night in the dark and low during the day. Hence, our findings support that NAS is more than a melatonin precursor, and that it can potently activate TrkB receptor.B rain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which includes nerve growth factor, NT-3, NT-4, and NT-5 (1). BDNF binding to TrkB triggers its dimerization through conformational changes and autophosphorylation of tyrosine residues in its intracellular domain, leading to activation of the three major downstream signaling cascades including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and phospholipase C-γ1 (2, 3). Through these pathways, BDNF mediates a variety of neuronal activities involved in neuronal survival, neurogenesis, synaptic plasticity, and so forth, and is implicated in numerous neurological diseases. For instance, loss of BDNF plays a major role in the pathophysiology of depression, and its restoration that induces neuroplastic changes may underlie the action of antidepressant efficacy (4-7).Daily rhythms in indole metabolism are a unique characteristic of the pineal gland. Pineal serotonin (5-HT) levels are higher during the day than at night. Conversely, pineal N-acetylserotonin (NAS) and melatonin levels are low during the day and high at night (8). The switch between day and night profiles of pineal indoles is predominantly regulated by the activity of arylalkylamine N-acetyltransferase (AANAT), which escalates at night 10-to 100-fold (9). AANAT metabolizes serotonin into NAS. AANAT mRNA is prominently expressed in the pineal gland and retina, and weakly in other regions of brain (10-12). NAS is mainly synthesized in the pineal gland, and is subsequently methylated by hydroxyindole-O-methyltransferase to synthesize melatonin. Until recently, NAS was considered only as the precursor of melatonin in the process of melatonin biosynthesis from serotonin. Melatonin is highly lipophilic and is not stored at significant levels. Accordingly, it is released into the blood immediately upon synthesis. Melatonin's role in the regulation of circadian rhythms and other functions is mediated primarily by me...

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“…Recent studies from our laboratory have demonstrated that both an NE-specific lesion and temporary blockade of badrenergic receptors remove the BDNF mRNA-enhancing effects of voluntary exercise Ivy et al, 2003). In addition, both NE-and 5-HT-selective receptor antagonists such as propranolol, ketanserin, and WAY-100635 reverse the BDNF-increasing effects of short-term treatment with the monoamine oxidase inhibitor, tranylcypromine (Ivy et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Much information has become available regarding the influence of physical exercise, antidepressant treatment, and other CNS-activating interventions on the expression of BDNF in the rat hippocampus. The combination of voluntary exercise and antidepressant treatment enhances the expression of hippocampal BDNF and that of its transcript variants in an additive manner (Russo-Neustadt et al, 1999), and evidence exists that monoaminergic activation is important for this effect Ivy et al, 2003). In the current study, we treated animals with the norepinephrine (NE)-selective antidepressant, reboxetine (Montgomery, 1999), and the highly serotonin (5-HT)-specific antidepressant, citalopram (Sanchez and Hyttel, 1999), in order to assess the relative contributions of NE and 5-HT activation to antidepressant and antidepressant/exercise-associated increases in hippocampal BDNF expression.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal Brain-Derived Neurotrophic Factor Expression Following Treatment with Reboxetine, Citalopram, and Physical Exercise

Russo-Neustadt

Alejandre

Garcia

et al. 2004

Neuropsychopharmacol

166

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The antidepressants, reboxetine and citalopram, were used in conjunction with voluntary physical exercise (wheel running) in order to assess the contribution of noradrenergic and serotonergic activation to enhancements in hippocampal brain-derived neurotrophic factor (BDNF) expression resulting from antidepressant treatment and exercise. Reboxetine (40 mg/kg/day), citalopram (10 mg/kg/day), voluntary physical activity, and the combination of antidepressants with exercise were applied to rats for a range of treatment intervals (2 to 14 days). Hippocampal BDNF transcription levels (full-length BDNF, as well as exons I-IV) were then assessed via in situ hybridization.Reboxetine treatment led to a rapid (evident at 2 days) enhancement in BDNF transcription in several hippocampal regions. This increase was also observed when reboxetine treatment was combined with voluntary physical activity for 2 weeks. Treatment with citalopram led to an increase in BDNF mRNA in only one hippocampal region (CA2) after short-term (2 days) treatment, and when combined with exercise, increased BDNF mRNA in the CA4 and dentate gyrus after 2 weeks. As reported in previous studies, voluntary physical activity enhanced BDNF transcription in several hippocampal areas, both on its own and in combination with antidepressant treatments. Examination of the levels of individual BDNF transcript variants influenced by each of these antidepressants revealed distinct patterns of expression in response to the various treatments, and showed that exercise-plus-antidepressant produced significant changes where antidepressant alone failed. Overall, treatment with the norephinephrine-selective antidepressant, reboxetine, in combination with exercise, led to both rapid and sustained increases in hippocampal BDNF mRNA expression. The serotonergic agent, citalopram, appeared to require longer treatment intervals in order to influence BDNF expression positively.

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Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant

Cited by 142 publications

References 53 publications

Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression

Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression

N -acetylserotonin activates TrkB receptor in a circadian rhythm

Hippocampal Brain-Derived Neurotrophic Factor Expression Following Treatment with Reboxetine, Citalopram, and Physical Exercise

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