Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

Phillips, Cristy

doi:10.1155/2017/7260130

Cited by 314 publications

(247 citation statements)

References 259 publications

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“…Though stressful life events are not thought to be the cause of BD itself, they can be a trigger for recurrence. Whereas stress decreases brain‐derived neurotrophic factor (BDNF) and spine density in cognition‐related brain areas, such as the cerebral cortex and hippocampus, stress increases BDNF and spine density in the amygdala and nucleus accumbens, which are related to emotion . This suggests that stress causes remodeling of neural circuits to adjust the emotion/cognition (E/C) balance to adapt to stressful environments.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Whereas stress decreases brain-derived neurotrophic factor (BDNF) and spine density in cognition-related brain areas, such as the cerebral cortex and hippocampus, stress increases BDNF and spine density in the amygdala and nucleus accumbens, which are related to emotion. 155,156 This suggests that stress causes remodeling of neural circuits to adjust the emotion/cognition (E/C) balance to adapt to stressful environments. In addition to antidepressants, 157 mood stabilizers 158 and atypical antipsychotics 159 also upregulate BDNF and possibly enhance plasticity.…”

Section: Environmental Factorsmentioning

confidence: 99%

“…Seasonal course of illness 96 Ongoing A small clinical study showed beneficial effect of ramelteon 237 Altered melatonin levels 205,206 Decreased acetylserotonin O-methyltransferase (ASMT) activity in lymphoblastoid cells 166 Emotion/cognition imbalance Enhanced response of amygdala and diminished response of DLPFC to emotional tasks [31][32][33][34] Stress differentially affects neurons in emotion-related and cognition-related circuits 155,156 Efficacy of cognitive behavioral therapy 243 Lithium normalizes reduced gray matter volume 17,19 Decreased cortical gray matter volume 19 Decreased spine density in DLPFC 49 Efficacy of neurofeedback targeting amygdala for depression 246 DLPFC, dorsolateral prefrontal cortex; ER, endoplasmic reticulum; iPSC, induced pluripotent stem cell; mPFC, medial prefrontal cortex; MRS, magnetic resonance spectroscopy.…”

Section: Photoperiodicitymentioning

confidence: 99%

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Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Kato

2019

Psychiatry Clin Neurosci

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Biological studies of bipolar disorder initially focused on the mechanism of action for antidepressants and antipsychotic drugs, and the roles of monoamines (e.g., serotonin, dopamine) have been extensively studied. Thereafter, based on the mechanism of action of lithium, intracellular signal transduction systems, including inositol metabolism and intracellular calcium signaling, have drawn attention. Involvement of intracellular calcium signaling has been supported by genetics and cellular studies. Elucidation of the neural circuits affected by calcium signaling abnormalities is critical, and our previous study suggested a role of the paraventricular thalamic nucleus. The genetic vulnerability of mitochondria causes calcium dysregulation and results in the hyperexcitability of serotonergic neurons, which are suggested to be susceptible to oxidative stress. Efficacy of anticonvulsants, animal studies of candidate genes, and studies using induced pluripotent stem cell‐derived neurons have suggested a relation between bipolar disorder and the hyperexcitability of neurons. Recent genetic findings suggest the roles of polyunsaturated acids. At the systems level, social rhythm therapy targets circadian rhythm abnormalities, and cognitive behavioral therapy may target emotion/cognition (E/C) imbalance. In the future, pharmacological and psychosocial treatments may be combined and optimized based on the biological basis of each patient, which will realize individualized treatment.

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Section: Animal Modelsmentioning

confidence: 99%

Section: Environmental Factorsmentioning

confidence: 99%

Section: Photoperiodicitymentioning

confidence: 99%

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Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Kato

2019

Psychiatry Clin Neurosci

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“…BDNF is abundant in the central and peripheral nervous systems of humans and found in both the serum and plasma (Lee & Kim, 2010). BDNF is vital to survival, growth, and maintenance of neurons (Phillips, 2017). There has been strong evidence that neuroplastic mechanisms that involve BDNF are severely altered in individuals with depression (Phillips, 2017).…”

Section: Background On Growth Factorsmentioning

confidence: 99%

“…BDNF is vital to survival, growth, and maintenance of neurons (Phillips, 2017). There has been strong evidence that neuroplastic mechanisms that involve BDNF are severely altered in individuals with depression (Phillips, 2017). Specifically, clinical evidence has demonstrated that stress-induced depression has resulted in changes in BDNF expression and function, therefore altering neuroplasticity (Phillips, 2017).…”

Section: Background On Growth Factorsmentioning

confidence: 99%

Fibroblast Growth Factor 2 (FGF2) is Necessary for the Antidepressant Effects of Fluoxetine in Chronically Stressed Mice

Shail¹

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Previous research has shown that fibroblast growth factor 2 protein (FGF2) can act as an anxiolytic and anti-depressive agent in rodents. Levels of hippocampal FGF2 and FGF2 receptors are decreased in post-mortem brains of individuals with mood disorders. No changes in FGF2 were noted in the post-mortem brains of individuals with mood disorders that were successfully treated with antidepressant medication. Mutations in the FGF2 gene in humans have predicted nonresponsiveness to the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs). FGF2 has pleiotropic effects such as promoting neuroplasticity and inflammation response. These findings suggest that FGF2 may be required for the therapeutic effects of antidepressant medications. To test this, we employed a rodent model of depressive behaviour, chronic variable stress (CVS) paired with antidepressant treatment (fluoxetine) in wild-type (WT) and FGF2 knockout mice (FGF2KO) and examined depressive and anxiety behaviors. We hypothesized that fluoxetine will reverse the effects of CVS on depressive and anxiety behaviours in wild-type mice, but not in FGF2KO, suggesting that the FGF2 gene is necessary for the therapeutic effects of fluoxetine. Because FGF2 has been previously shown to modify HPA activity through hippocampal glucocorticoid receptors (GR), we also examined levels of GR. We predicted that there would be a decrease in GR in response to CVS, as seen in previous studies, with a further decrease in the FGF2KO mice. Changes in cytokine levels have also been implicated in depression and are generally reversed with fluoxetine therefore we also examined whether these effects were FGF2 dependant. We believed there would be increases in levels of EGF, VEGF, BDNF, and FGF2 in stressed wildtype mice treated with fluoxetine, however we hypothesized that we would not see these changes in FGF2KO mice. Whether astroglia, astroglial functions, or HPA changes are the downstream target of FGF2-mediated changes induced by fluoxetine remains to be 3 determined, however, the current study reaffirms the potential of FGF2 as a novel therapeutic target in the treatment of depression and anxiety disorders. 4

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Structure‐based design of peptidomimetic inhibitors of PSD‐95 with improved affinity for the PDZ3 domain

Naik,

et al. 2023

FEBS Letters

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Aberrant brain‐derived neurotrophic factor (BDNF) signaling has been proposed to contribute to the pathophysiology of depression and other neurological disorders such as Angelman syndrome. We have previously shown that targeting the tropomyosin receptor kinase B/postsynaptic density protein‐95 (PSD‐95) nexus in the BDNF signaling pathway by peptidomimetic inhibitors is a promising approach for therapeutic intervention. Here, we used structure‐based knowledge to develop a new Syn3 peptidomimetic compound series that fuses peptides derived from the PSD‐95‐binding protein SynGAP to our prototype compound CN2097. The new compounds target the PSD‐95 PDZ3 domain and adjoining αC helix to achieve bivalent binding that results in up to 7‐fold stronger affinity compared to CN2097. These compounds were designed to improve CN2097 specificity for the PSD‐95 PDZ3 domain, and structure–activity relationship studies were performed to improve their resistance to proteolysis.

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Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

Cited by 314 publications

References 259 publications

Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Fibroblast Growth Factor 2 (FGF2) is Necessary for the Antidepressant Effects of Fluoxetine in Chronically Stressed Mice

Structure‐based design of peptidomimetic inhibitors of PSD‐95 with improved affinity for the PDZ3 domain

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