VGF, a New Player in Antidepressant Action?

Malberg, Jessica E.; Monteggia, Lisa M.

doi:10.1126/stke.118pe19

Cited by 27 publications

(21 citation statements)

References 22 publications

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“…These observations were later confirmed by a large series of studies in Siberian hamsters and mice [2,9,10,11,12,13,14]. Thereafter, different experimental studies proposed that these peptides were also involved in the control of gastrointestinal function, water balance, endocrine and exocrine pancreatic secretion, neural and pancreatic islet β-cell survival, inflammatory pain, stress responses and emotional behavior [15,16,17,18,19,20,21,22,23]. …”

Section: Introductionmentioning

confidence: 80%

Characterization of the Reproductive Effects of the Vgf-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

et al. 2013

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Background: VGF (non-acronymic), a protein expressed in the hypothalamus and pituitary, is involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Previous studies of our group reported that this molecule participates also in the regulation of reproductive function in male rats, with predominant stimulatory effects. Methods: We report herein a series of studies on the reproductive effects of TLQP-21 in female rats, as evaluated by a combination of in vivo and in vitro analyses. Results: TLQP-21 modestly increased serum LH levels after systemic administration and directly stimulated pituitary LH and FSH secretion in prepubertal female rats, while acute central injection of TLQP-21 was unable to modify LH secretion at this age. Repeated central administration of TLQP-21 during the pubertal transition (between PND-28 and -35) to female rats fed ad libitum advanced the timing of vaginal opening and increased the percentage of animals with signs of ovulation. Moreover, an analogous treatment slightly enhanced ovarian maturation in pubertal female rats subjected to chronic undernutrition, but was unable to rescue the delay of vaginal opening induced by food deprivation. In addition, TLQP-21 oppositely modified LH secretion in adult female rats depending on the stage of the ovarian cycle: it stimulated LH secretion when injected in the morning of diestrus and decreased the magnitude of the preovulatory LH (but not FSH) surge when injected in the afternoon of proestrus. Conclusions: Our data are the first to document the potential involvement of TLQP-21 in the control of reproductive function in female rats.

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Section: Introductionmentioning

confidence: 80%

Characterization of the Reproductive Effects of the Vgf-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

et al. 2013

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“…The roles of VGF in depression and antidepressant actions (Thakker-Varia and Alder 2009;Malberg and Monteggia 2008) suggest that the upregulation of VGF expression by fluoxetine in astrocytes may contribute to its antidepressant actions.…”

Section: Resultsmentioning

confidence: 99%

Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes

et al. 2011

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Rationale The pharmacological actions of most antidepressants are ascribed to the modulation of serotonergic and/or noradrenergic transmission in the brain. During therapeutic treatment for major depression, fluoxetine, one of the most commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, accumulates in the brain, suggesting that fluoxetine may interact with additional targets. In this context, there is increasing evidence that astrocytes are involved in the pathophysiology of major depression. Objectives The aim of this study was to examine the effects of fluoxetine on the expression of neurotrophic/growth factors that have antidepressant properties and on glucose metabolism in cultured cortical astrocytes. Results Treatment of astrocytes with fluoxetine and paroxetine, another SSRI antidepressant, upregulated brainderived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and VGF mRNA expression. In contrast, the tricyclic antidepressants desipramine and imipramine did not affect the expression of these neurotrophic/growth factors. Analysis of the effects of fluoxetine on glucose metabolism revealed that fluoxetine reduces glycogen levels and increases glucose utilization and lactate release by astrocytes. Similar data were obtained with paroxetine, whereas imipramine and desipramine did not regulate glucose metabolism in this glial cell population. Our results also indicate that the effects of fluoxetine and paroxetine on glucose utilization, lactate release, and expression of BDNF, VEGF, and VGF are not mediated by serotonin-dependent mechanisms. Conclusions These data suggest that, by increasing the expression of specific astrocyte-derived neurotrophic factors and lactate release from astrocytes, fluoxetine may contribute to normalize the trophic and metabolic support to neurons in major depression.

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“…Examples are NCAM, vascular endothelial growth factor (VEGF), VGF (not an acronym), and fibroblast growth factor receptor (FGFR) (Klementiev et al 2007;Sandi and Bisaz 2007;Malberg and Monteggia 2008). BDNF, on the other hand, does not appear to have antidepressant activities.…”

Section: Neuroprogression As a New Drug Target In Depressionmentioning

confidence: 96%

New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

Maes

Fišar

Medina³

et al. 2012

Inflammopharmacol

291

196

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This paper reviews new drug targets in the treatment of depression and new drug candidates to treat depression. Depression is characterized by aberrations in six intertwined pathways: (1) inflammatory pathways as indicated by increased levels of proinflammatory cytokines, e.g. interleukin-1 (IL-1), IL-6, and tumour necrosis factor α. (2) Activation of cell-mediated immune pathways as indicated by an increased production of interferon γ and neopterin. (3) Increased reactive oxygen and nitrogen species and damage by oxidative and nitrosative stress (O&NS), including lipid peroxidation, damage to DNA, proteins and mitochondria. (4) Lowered levels of key antioxidants, such as coenzyme Q10, zinc, vitamin E, glutathione, and glutathione peroxidase. (5) Damage to mitochondria and mitochondrial DNA and reduced activity of respiratory chain enzymes and adenosine triphosphate production. (6) Neuroprogression, which is the progressive process of neurodegeneration, apoptosis, and reduced neurogenesis and neuronal plasticity, phenomena that are probably caused by inflammation and O&NS. Antidepressants tend to normalize the above six pathways. Targeting these pathways has the potential to yield antidepressant effects, e.g. using cytokine antagonists, minocycline, Cox-2 inhibitors, statins, acetylsalicylic acid, ketamine, ω3 poly-unsaturated fatty acids, antioxidants, and neurotrophic factors. These six pathways offer new, pathophysiologically guided drug targets suggesting that novel therapies could be developed that target these six pathways simultaneously. Both nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and glycogen synthase kinase-3 (GSK-3) inhibitors target the six above-mentioned pathways. GSK-3 inhibitors have antidepressant effects in animal models of depression. Nrf2 activators and GSK-3 inhibitors have the potential to be advanced to phase-2 clinical trials to examine whether they augment the efficacy of antidepressants or are useful as monotherapy.

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VGF, a New Player in Antidepressant Action?

Cited by 27 publications

References 22 publications

Characterization of the Reproductive Effects of the <b><i>Vgf</i></b>-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

Characterization of the Reproductive Effects of the <b><i>Vgf</i></b>-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes

New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

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