Decreased levels of whole blood glial cell line-derived neurotrophic factor (GDNF) in remitted patients with mood disorders

Takebayashi, Minoru; Hisaoka, Kazue; Nishida, Akira; Tsuchioka, Mami; Miyoshi, Izuru; Kozuru, Tosirou; Hikasa, Satoshi; Okamoto, Yasumasa; Shinno, Hideto; Morinobu, Shigeru; Yamawaki, Shigeto

doi:10.1017/s1461145705006085

Cited by 118 publications

(66 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, we recently reported that total GDNF levels in whole blood in patients with mood disorders were significantly lower than those in healthy control subjects (Takebayashi et al, 2006). These results suggest that lower GDNF levels might be involved in the pathophysiology of mood disorders, and increase of GDNF by antidepressants might be involved in their therapeutic action.…”

mentioning

confidence: 88%

“…Recent findings showed that several neurotrophic factors such as BDNF, neurotrophin-3, FGF, and GDNF are altered in post-mortem brain, cerebrospinal fluid, or blood from patients with mood disorders (Hock et al, 2000;Shimizu et al, 2003;Evans et al, 2004;Takebayashi et al, 2006). These observations suggest that the dysregulation of multiple neurotrophic/growth factor systems might be involved in the etiology of mood disorders.…”

Section: Mechanism Of Gdnf Production By Antidepressants 155mentioning

confidence: 99%

See 1 more Smart Citation

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Hisaoka¹,

Takebayashi²,

Tsuchioka³

et al. 2007

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Recent studies show that neuronal and glial plasticity are important for therapeutic action of antidepressants. We previously reported that antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production in rat C6 glioma cells (C6 cells). Here, we found that amitriptyline, a tricyclic antidepressant, increased both GDNF mRNA expression and release, which were selectively and completely inhibited by mitogen-activated protein kinase kinase inhibitors. Indeed, treatment of amitriptyline rapidly increased extracellular signal-regulated kinase (ERK) activity, as well as p38 mitogen-activated protein kinase and c-Jun NH 2 -terminal kinase activities. Furthermore, different classes of antidepressants also rapidly increased ERK activity. The extent of acute ERK activation and GDNF release were significantly correlated to each other in individual antidepressants, suggesting an important role of acute ERK activation in GDNF production. Furthermore, antidepressants increased the acute ERK activation and GDNF mRNA expression in normal human astrocytes as well as C6 cells. Although 5-hydroxytryptamine (serotonin) (5-HT), but not noradrenaline or dopamine, increased ERK activation and GDNF release via 5-HT 2A receptors, ketanserin, a 5-HT 2A receptor antagonist, did not have any effect on the amitriptyline-induced ERK activation. Thus, GDNF production by amitriptyline was independent of monoamine. Both of the amitriptyline-induced ERK activation and GDNF mRNA expression were blocked by genistein, a general protein tyrosine kinase (PTK) inhibitor. Actually, we found that amitriptyline acutely increased phosphorylation levels of several phosphotyrosine-containing proteins. Taken together, these findings indicate that ERK activation through PTK regulates antidepressant-induced GDNF production and that the GDNF production in glial cells may be a novel action of the antidepressant, which is independent of monoamine.Major depression is a common and severe illness affecting a large number of individuals during their lifetime, and it is primarily treated with antidepressants. Most of the antidepressants are known to inhibit 5-hydroxytryptamine (serotonin, 5-HT) and/or noradrenaline (NA) reuptake; however, the efficacy of these antidepressants cannot be solely explained by their actions on the monoaminergic system. The molecular and cellular adaptations that underlie the therapeutic action of antidepressants have remained obscure. ; JNK, c-Jun NH 2 -terminal protein kinase; LDH, lactate dehydrogenase; ANOVA, analysis of variance; PLSD, protected least significant difference; HSD, honestly significant difference; MEK, mitogen-activated protein kinase kinase; PKA, protein kinase A; PKC, protein kinase C; DA, dopamine; PI3K, phosphoinositide-3 kinase; SP600125, anthra(1,9-cd)pyrazol-6(2H)-one.

show abstract

mentioning

confidence: 88%

Section: Mechanism Of Gdnf Production By Antidepressants 155mentioning

confidence: 99%

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Hisaoka¹,

Takebayashi²,

Tsuchioka³

et al. 2007

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, both clinical and preclinical animal studies have demonstrated that multiple neurotrophic/growth factors, such as glial cell line-derived neu-rotrophic factor (GDNF), a member of the transforming growth factor ␤ superfamily, have been proposed to play an important role in the therapeutic effect of antidepressants (4,5). Glial cell line-derived neurotrophic factor has been shown to be decreased in the peripheral blood of patients with MDD (6), whereas blood levels of GDNF in MDD are increased after antidepressant treatment (7). These findings suggest that modulating GDNF production may be a key therapeutic effect of antidepressants.…”

Section: Major Depressive Disorder (Mdd)mentioning

confidence: 99%

Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells

Hisaoka-Nakashima

Miyano

Matsumoto

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: A significant non-neural, monoamine-independent mechanism underlies the antidepressant effect of amitriptyline. Results: Amitriptyline-evoked GDNF production is mediated by pertussis toxin (PTX)-sensitive G␣ i/o . Conclusion: PTX-sensitive G␣ i/o activation is critical for the cascade that underpins the biological effect of amitriptyline. Significance: Further elaboration of the intracellular mechanism of amitriptyline could lead to greater understanding of depression and novel antidepressant treatments.

show abstract

“…Second, GDNF increases the proliferation of neural progenitors in the adult DG in vivo [11]. Third, the levels of whole blood GDNF in patients with mood disorders are significantly lower than those in healthy control subjects [22]. Fourth, STAT3 might mediate astrogliogenesis from neural precursor cell [23,24,25,26,27] and GDNF-dependent mechanisms might exist for activation of STAT3 [28,29].…”

Section: Introductionmentioning

confidence: 99%

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

Boku

Nakagawa

Takamura

et al. 2013

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

show abstract

Decreased levels of whole blood glial cell line-derived neurotrophic factor (GDNF) in remitted patients with mood disorders

Cited by 118 publications

References 12 publications

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

Contact Info

Product

Resources

About