Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?

Miranda, Aline Silva de; Barros, João Luís Vieira Monteiro de; Teixeira, Antônio Lúcio

doi:10.1080/14728222.2020.1846720

Cited by 27 publications

(19 citation statements)

References 129 publications

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“…Furthermore, neurotrophins, especially BDNF and NT-3, have been investigated in mood disorders and found to play a role in depression and anxiety. 28 He et al showed that serum BDNF levels were lower and negatively associated with depressive symptoms in young Chinese adults with acne vulgaris. 13 They also found that the severity of the disease was not related to depression scores in their acne patients, as did we in LSC.…”

Section: Discussionmentioning

confidence: 99%

More than a skin disease: stress, depression, anxiety levels, and serum neurotrophins in lichen simplex chronicus

Altunay¹,

Özkur²,

Uğurer³

et al. 2021

Anais Brasileiros de Dermatologia

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Background Lichen simplex chronicus is a dermatological condition due to excessive scratching, with few studies on psychoneuroimmunology. Objective We aimed to estimate the levels of stress, depression, and anxiety, and to measure serum levels of neurotrophins in patients with lichen simplex chronicus, and to correlate these parameters with the severity of the disease and pruritus. Methods Thirty-six patients with lichen simplex chronicus and 36 age- and sex-matched healthy controls were included. Each participant was administered the Hospital Anxiety and Depression Scale and Perceived Stress Scale questionnaires, along with a visual analog scale for pruritus. Levels of neurotrophins (brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor) were determined by ELISA assays. Results The scores of Perceived Stress Scale-10, Hospital Anxiety and Depression Scale were statistically higher in patients (p < 0.05 for all). The serum levels of all neurotrophins were significantly lower in patients compared to healthy controls (p < 0.05 for all). Disease severity showed no correlation with all four neurotrophins. In linear regression models applied for increased visual analog scale-pruritus scores and disease severity these two variables were statistically significant predictors (p = 0.043). Study limitations A direct causal relationship was not addressed. Conclusion Lichen simplex chronicus patients are at risk of increased levels of stress, anxiety, depression, and present decreased levels of neurotrophins, that may suggest a role in the pathophysiology of this disorder.

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Section: Discussionmentioning

confidence: 99%

More than a skin disease: stress, depression, anxiety levels, and serum neurotrophins in lichen simplex chronicus

Altunay¹,

Özkur²,

Uğurer³

et al. 2021

Anais Brasileiros de Dermatologia

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“…NT-3 is thought to play a role in the neurobiological processes associated with mood and anxiety disorders. In recent years, it has been proposed that NT-3 is a potential pharmacological target for mood disorders due to its effects on monoamine neurotransmitters, regulation of synaptic plasticity and neurogenesis, enhancement of BDNF signaling, and regulation of the HPA axis ( de Miranda et al, 2020 ). There are even fewer studies on the role of NT-4/5 in depression.…”

Section: Discussionmentioning

confidence: 99%

“…As described above, improvements in the production of monoamine and serotonin, the HPA axis, and expression of neurotrophic factors have been proposed as treatments for depression ( Jacobson and Sapolsky, 1991 ; Smith et al, 1995 ; Manji et al, 2001 ; Nestler et al, 2002 ; Okamoto et al, 2003 ; Adams et al, 2008 ; Otsuki et al, 2008 ; Sanacora et al, 2008 ; Liu et al, 2017 ; de Miranda et al, 2020 ). Our studies revealed that acupuncture stimulation ameliorates SDS-induced immobility in mice.…”

Section: Discussionmentioning

confidence: 99%

Acupuncture Treatment for Social Defeat Stress

Koyama

Takagi

Tanahashi

et al. 2021

Front. Behav. Neurosci.

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Depression is a mood disorder characterized by disordered affect, thoughts, cognition, and behavior. Antidepressant therapy is often the primary treatment for depression. However, antidepressant therapy may cause unwanted side effects, and its effects are slow. Therefore, some patients are seeking alternative treatments for depression, such as acupuncture. However, there are many unclear points regarding the mechanism of the effect of acupuncture on depression. In recent years, we have reported that acupuncture improves the symptoms of mild depression induced by water-immersion stress in a rat model and depression induced by forced swimming in a mouse model. In this study, we examined the effect of acupuncture on the symptoms of social defeat stress (SDS)-induced depression in mice that most closely resemble human symptoms. In this study, we investigated the preventive and therapeutic effects of acupuncture as part of GV20 “Bai-Hui” and Ex-HN3 “Yintang” on model mice with depression induced by SDS. To examine the mechanism of the preventive and therapeutic effects of acupuncture on depression model mice, we examined the expression of neurotrophic factors in the brains of SDS mice. Two weeks of simultaneous acupuncture stimulation as part of GV20 and Ex-HN3 restored SDS-reduced brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and NT-4/5 expression, which was not observed with antidepressants. In contrast, acupuncture stimulation suppressed nerve growth factor (NGF) expression induced by SDS. These results suggest that acupuncture treatment could be effective in correcting the imbalance in the expression of neurotrophic factors. Furthermore, the effects of acupuncture on the expression of neurotrophic factors appear earlier than those of antidepressants, suggesting that it may be a useful treatment for depression.

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“…Recent studies have revealed that numerous anxiolytic substances, including endogenous neurotransmitters, anxiolytic drugs, and nutraceuticals, are also neurotrophic in that they also activate the brain derived neurotrophic factor (BDNF) pathway, the neurotrophin-3 (NT-3) pathways and the nerve growth factor (NGF) pathway by binding to or potentiating the TRKA -C neurotrophin receptors and directly activating the ERK1/2 signaling pathway leading to neuroplasticity [26][27][28][29][30][31][32][33][34][35][36][37]. This is important because neurotrophins can regulate neuroplasticity not only during development but also during learning and the establishment of memories [35][36][37].…”

Section: Introductionmentioning

confidence: 99%

“…The changes in cell shape associated with the establishment of new neurites and therefore potentially new connections is known as neuroplasticity [35][36][37]. Recent attention has been brought to the idea that in so far as anxiety is related to the memories of trauma and the establishment of a learned threat level in the perception of stressors through neuroplasticity, perhaps anxiolytic phytochemicals with neurotrophic activity can be used to reduce anxiety not only through changes neurotransmitter activity, but also by providing the plasticity required to relearn and reduce the emotional value ascribed to a stressor thereby also facilitating the reduction in anxiety [26][27][28][29][30][31][32][33][34]. Therefore anxiolytic phytochemical neurotrophins are important because they offer a new area of research into not simply adjusting neurotransmitter activity, but to the development of natural treatments and drugs that can actually reverse the neurocircuitry associated with anxiety through neuroplasticity and relearning.…”

Section: Introductionmentioning

confidence: 99%

Physiological and Cellular Targets of Neurotrophic Anxiolytic Phytochemicals in Food and Dietary Supplements

Weeks¹,

Weeks²,

Kim³

et al. 2021

Functional Foods - Phytochemicals and Health Promoting Potential

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Diet impacts anxiety in two main ways. First anxiety can be caused by deficiencies in antioxidants, neurotransmitter precursors, amino acids, cations and vitamins and other cofactors. Second, anxiety can be reduced by anxiolytic nutraceuticals which are food molecules that bind to molecular targets of the amygdala and the hypothalamus-pituitary–adrenal axis (HPA-axis). Anxiety is a feeling of fear that arises from a perceived threat and can be a beneficial coping mechanism to threats and stressors. However excessive anxiety is a disorder that interferes with healthy responses to stressors. The amygdala is responsible for assigning value to a threat or stressor and triggering the HPA-axis to support the body wide system responses to the threat. The amygdala also communicates with the neuroplastic learning and memory centers of the hippocampus to fix or set a learned value to the threat. Interestingly, many anxiolytic nutraceuticals that show benefits in human clinical trials have neurotrophic activity and increase neuronal plasticity. Moreover, anxiolytic nutraceuticals either act like the neurotrophins, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF and neurotrophin-3 (NT3) by either directly binding to or potentiating the tyrosine receptor kinase (TRK) family of receptors (TRKA, TRKB and TRKC) and activating the ERK1/2 signal transduction pathway associated with neurite outgrowth and neural plasticity. This chapter will explore the neuritogenic activity of clinically proven plant-based anxiolytic nutraceuticals and examine the commonality of TRKA-C receptors and the ERK1/2 signaling pathway in the pharmacological and nutraceutical treatment of anxiety disorders.

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Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?

Cited by 27 publications

References 129 publications

More than a skin disease: stress, depression, anxiety levels, and serum neurotrophins in lichen simplex chronicus

More than a skin disease: stress, depression, anxiety levels, and serum neurotrophins in lichen simplex chronicus

Acupuncture Treatment for Social Defeat Stress

Physiological and Cellular Targets of Neurotrophic Anxiolytic Phytochemicals in Food and Dietary Supplements

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