The involvement of BDNF-CREB signaling pathways in the pharmacological mechanism of combined SSRI- antipsychotic treatment in schizophrenia

Einoch, Reef; Weinreb, Orly; Mandiuk, Nina; Youdim, Moussa B. H.; Bilker, Warren B.; Silver, Henry

doi:10.1016/j.euroneuro.2017.03.005

Cited by 31 publications

(17 citation statements)

References 48 publications

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“…However, basal corticosterone levels were not different between the groups. Furthermore, SSRIs have been shown to affect a plethora of cellular pathways, some of which seem independent of their function as SSRI (Einoch et al, 2017 ; Eskelund et al, 2017 ). Similarly, the molecular functions of FKBP51 also largely exceed its role as Hsp90/GR co-chaperone (Balsevich et al, 2017 ; Fries et al, 2017 ; Hamilton et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of the Psychiatric Risk Factor FKBP51 Alters Efficiency of Common Antidepressant Drugs

Pöhlmann

Häusl

Harbich

et al. 2018

Front. Behav. Neurosci.

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Despite a growing body of research over the last few decades, mental disorders, including anxiety disorders or depression, are still one of the most prevalent and hardest to treat health burdens worldwide. Since pharmacological treatment with a single drug is often rather ineffective, approaches such as co-medication with functionally diverse antidepressants (ADs) have been discussed and tried more recently. Besides classical ADs, there is a growing number of candidate targets identified as potential starting points for new treatment methods. One of these candidates, the FK506 binding protein 51 (FKBP51) is linked to a number of psychiatric disorders in humans. In this study, we used SAFit2—a newly developed modulator of FKBP51, which has shown promising results in rodent models for stress-related disorders delivered in a depot formulation. We combined SAFit2 with the commonly prescribed selective serotonin reuptake inhibitor (SSRI) escitalopram and performed basic behavioral characterization in a mouse model. Remarkably, co-application of SAFit2 lowered the efficacy of escitalopram in anxiety-related tests but improved stress coping behavior. Given the fact that mental diseases such as anxiety disorders or depression can be divided into different sub-categories, some of which more or less prone to stress, SAFit2 could indeed be a highly beneficial co-medication in very specific cases. This study could be a first, promising step towards the use of FKBP51 modulators as potent and specific enhancers of AD efficiency for subclasses of patients in the future.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of the Psychiatric Risk Factor FKBP51 Alters Efficiency of Common Antidepressant Drugs

Pöhlmann

Häusl

Harbich

et al. 2018

Front. Behav. Neurosci.

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“…(1:1,000, Abcam, #ab32375, Cambridge, MA) antibody was purchased from Abcam; rabbit anti-GAPDH (1:5,000; Cell Signaling Technology, #5174S, Danvers, MA) antibody was purchased from Cell Signaling Technology; mouse anti-parvalbumin (PV, 1:2,000, Swant, #PV235, Bellinzona, Switzerland) antibody was purchased from Swant; goat anti-Doublecortin (DCX, 1:100; Santa Cruz, #SC-8066, CA) antibody was purchased from Santa Cruz; mouse anti-BrdU (1:200; Roche, #11170376001, IN) antibody was purchased from Roche; rabbit anti-NeuN (1:1,000, Millipore, #MABN140, Darmstadt, Germany) antibody was purchased from Millipore; rabbit anti-BDNF (1:1,000; Abcam, #ab108319, Cambridge, MA) antibody (Einoch et al, 2017;Qian et al, 2017) was purchased from Abcam; rabbit anti-BDNF (1:200; Alomone, #ANT010, Jerusalem, Israel) antibody (Fulmer et al, 2014;Wattananit et al, 2016) was purchased from Alomone; rabbit anti-TrkB (1:1,000; Cell Signaling Technology, #4603S, Danvers, MA) antibody (Pandya et al, 2017;Qian et al, 2017) (Fazzari et al, 2010) was specially used for immunohistochemistry has previously been demonstrated (Bean et al, 2014;Fazzari et al, 2010;Ozcelik et al, 2002;Woo, Lee, Yu, Song, & Baik, 2007;Yin et al, 2013;Zhang et al, 2017).…”

Section: Antibodiesmentioning

confidence: 99%

Ablation of ErbB4 in parvalbumin‐positive interneurons inhibits adult hippocampal neurogenesis through down‐regulating BDNF/TrkB expression

Zhang

Mei

et al. 2018

J of Comparative Neurology

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Parvalbumin (PV) positive interneurons in the subgranular zone (SGZ) can regulate adult hippocampal neurogenesis. ErbB4 is mainly expressed in PV neurons in the hippocampus and is crucial for keeping normal function of PV neurons. However, whether ErbB4 in PV interneurons affects the adult hippocampal neurogenesis remains unknown. In the present study, we deleted ErbB4 specifically in PV neurons by crossing PV‐Cre mice with ErbB4f/f mice. Results of BrdU labeling and NeuN staining revealed that the proliferation of neural progenitors was increased but the survival and maturation of newborn neurons were decreased in the hippocampus of mice after deleting ErbB4 in PV neurons, suggesting that ErbB4 in PV neurons is closely associated with the process of adult hippocampal neurogenesis. Interestingly, the expression of brain‐derived neurotrophic factor (BDNF) and its receptor, tropomyosin‐related kinase B (TrkB), was significantly decreased in the hippocampus of ErbB4‐deleted mice. Together, our data suggested that ErbB4 in PV neurons might modulate adult hippocampal neurogenesis by affecting BDNF–TrkB signaling pathway.

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“…Fluoxetine has been used to treat depression in schizophrenia and has shown to be effective in augmenting therapeutic effects of second-generation antipsychotics in schizophrenia [ 4 ]. BDNF signaling pathway may be involved in the pharmacological mechanism of combined SSRI-antipsychotic treatment in schizophrenia [ 18 ]. BDNF, a neuroprotective protein, is the most abundant neurotrophin in the brain, and its expression in hippocampus and prefrontal cortex can be affected by prenatal stress [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine attenuates prepulse inhibition deficit induced by neonatal administration of MK-801 in mice

Yang

Liu²,

Yuan³

et al. 2020

NeuroReport

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Increasing evidence supports schizophrenia may be a neurodevelopmental and neurodegenerative disorder. Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to have neuroprotective effects and be effective in treating neurodegenerative disorders including schizophrenia. The objective of the present study was to evaluate the effect and underlying neuroprotective mechanism of fluoxetine on the sensorimotor gating deficit, a schizophrenia-like behavior in a neurodevelopmental schizophrenic mouse model induced by MK-801, an N -methyl- d -aspartate glutamate receptor antagonist. On postnatal day 7, mouse pups were treated with a total seven subcutaneous daily injections of MK-801 (1 mg/kg/day), followed by intraperitoneal injection of fluoxetine (5 or 10 mg/kg/day) starting on postnatal day 14 in the MK-801-injected mice for 4 weeks. The sensorimotor gating deficit in mice was measured by prepulse inhibition (PPI) behavioral test on postnatal day 43. After the behavioral test, the protein expression of brain-derived neurotrophic factor (BDNF) was measured by western blot or ELISA in the frontal cortex of mice. Our results showed fluoxetine attenuated PPI deficit and the decrease of cerebral BDNF expression in the MK-801-injected mice. These results suggest that fluoxetine can be used to treat sensorimotor gating deficit in a neurodevelopmental mouse model of schizophrenia, and the attenuating effect of fluoxetine on sensorimotor gating deficit may be related to fluoxetine’s neuroprotective effect targeting on the modulation of cerebral BDNF.

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The involvement of BDNF-CREB signaling pathways in the pharmacological mechanism of combined SSRI- antipsychotic treatment in schizophrenia

Cited by 31 publications

References 48 publications

Pharmacological Modulation of the Psychiatric Risk Factor FKBP51 Alters Efficiency of Common Antidepressant Drugs

Pharmacological Modulation of the Psychiatric Risk Factor FKBP51 Alters Efficiency of Common Antidepressant Drugs

Ablation of ErbB4 in parvalbumin‐positive interneurons inhibits adult hippocampal neurogenesis through down‐regulating BDNF/TrkB expression

Fluoxetine attenuates prepulse inhibition deficit induced by neonatal administration of MK-801 in mice

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