HBK-15 protects mice from stress-induced behavioral disturbances and changes in corticosterone, BDNF, and NGF levels

Pytka, Karolina; Głuch‐Lutwin, Monika; Kotańska, Magdalena; Żmudzka, Elżbieta; Jakubczyk, Magdalena; Waszkielewicz, Anna M.; Janiszewska, Paulina; Walczak, Maria

doi:10.1016/j.bbr.2017.06.032

Cited by 17 publications

(21 citation statements)

References 71 publications

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“…Several studies employing the unpredictable chronic mild stress model in adult male rats and mice report largely consistent effects – anhedonic- and despair-like behavior, reduced BDNF in the PFC, increased blood serum CORT levels, and adrenal hypertrophy (indicative of an overactive HPA axis) (Jin et al, 2015; Abdul Shukkoor et al, 2016; Pytka et al, 2017; Zu et al, 2017) (table 3). These patterns are also seen in female mice (Filho et al, 2015).…”

Section: Stress-induced Alterations In Pfc Trkb and Grmentioning

confidence: 90%

Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts

Barfield

Gourley

2018

Neuroscience & Biobehavioral Reviews

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The tyrosine receptor kinase B (trkB) and glucocorticoid receptor (GR) regulate neuron structure and function and the hormonal stress response. Meanwhile, disruption of trkB and GR activity (e.g., by chronic stress) can perturb neuronal morphology in cortico-limbic regions implicated in stressor-related illnesses like depression. Further, several of the short- and long-term neurobehavioral consequences of stress depend on the developmental timing and context of stressor exposure. We review how the levels and activities of trkB and GR in the prefrontal cortex (PFC) change during development, interact, are modulated by stress, and are implicated in depression. We review evidence that trkB- and GR-mediated signaling events impact the density and morphology of dendritic spines, the primary sites of excitatory synapses in the brain, highlighting effects in adolescents when possible. Finally, we review the role of neurotrophin and glucocorticoid systems in stress-related metaplasticity. We argue that better understanding the long-term effects of developmental stressors on PFC trkB, GR, and related factors may yield insights into risk for chronic, remitting depression and related neuropsychiatric illnesses.

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Section: Stress-induced Alterations In Pfc Trkb and Grmentioning

confidence: 90%

Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts

Barfield

Gourley

2018

Neuroscience & Biobehavioral Reviews

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“…Fixed tissues were dried for 5 min before the measurement of their weight to avoid errors in the weighing of the remnants of the fixing solution. The relative adrenal gland weights (mg per pair of dry glands/total body weight of each mouse in g) were calculated as described previously [32].…”

Section: Immunohistochemical Determination Of Neuronalmentioning

confidence: 99%

“…The first implies negative feedback on the HPA axis that remains even under the hyperactivity that is present after CUS [36] and second, a decompensation where the adrenal cortex cannot meet the demand for glucocorticoids and it decreases even though there is a high concentration of the hormone adrenocorticotropin (ACTH) [37]. Other pieces of evidence propose the measurement of the relative weight of the adrenal glands as an indicator of dysregulation of the HPA axis in various models of depression [32]. Animals subjected to a CUS protocol exhibit increased levels of corticosterone and an increase in adrenal gland weight [38].…”

Section: Effect Of Urb597 On Biomarkers In the Cus Modelmentioning

confidence: 99%

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure

Tejeda-Martínez

Viveros–Paredes

Hidalgo-Franco

et al. 2021

Behavioural Neurology

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Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.

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“…The number of animals in groups was based on our previous experiments (Pytka et al 2017). Results are presented as box plots or means ± SEM.…”

Section: Discussionmentioning

confidence: 99%

The selective 5-HT1A receptor biased agonists, F15599 and F13714, show antidepressant-like properties after a single administration in the mouse model of unpredictable chronic mild stress

et al. 2021

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Rationale The prevalence of depression is ever-increasing throughout the population. However, available treatments are ineffective in around one-third of patients and there is a need for more effective and safer drugs. Objectives The antidepressant-like and procognitive effects of the “biased agonists” F15599 (also known as NLX-101) which preferentially targets postsynaptic 5-HT1A receptors and F13714, which targets 5-HT1A autoreceptors, were investigated in mice. Methods Antidepressant-like properties of the compounds and their effect on cognitive functions were assessed using the forced swim test (FST) and the novel object recognition (NOR), respectively. Next, we induced a depressive-like state by an unpredictable chronic mild stress (UCMS) procedure to test the compounds’ activity in the depression model, followed by measures of sucrose preference, FST, and locomotor activity. Levels of phosphorylated cyclic AMP response element-binding protein (p-CREB) and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) were also determined. Results F15599 reduced immobility time in the FST over a wider dose-range (2 to 16 mg/kg po) than F13714 (2 and 4 mg/kg po), suggesting accentuated antidepressant-like properties in mice. F15599 did not disrupt long-term memory consolidation in the NOR at any dose tested, while F13714 impaired memory formation, notably at higher doses (4–16 mg/kg). In UCMS mice, a single administration of F15599 and F13714 was sufficient to robustly normalize depressive-like behavior in the FST but did not rescue disrupted sucrose preference. Both F15599 and F13714 rescued cortical and hippocampal deficits in p-ERK1/2 levels of UCMS mice but did not influence the p-CREB levels. Conclusions Our studies showed that 5-HT1A receptor biased agonists such as F13714 and especially F15599, due to its less pronounced side effects, might have potential as fast-acting antidepressants.

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HBK-15 protects mice from stress-induced behavioral disturbances and changes in corticosterone, BDNF, and NGF levels

Cited by 17 publications

References 71 publications

Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts

Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure

The selective 5-HT1A receptor biased agonists, F15599 and F13714, show antidepressant-like properties after a single administration in the mouse model of unpredictable chronic mild stress

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