scholarly journals Antidepressant and Anxiolytic-Like Effects of the Stem Bark Extract of Fraxinus rhynchophylla Hance and Its Components in a Mouse Model of Depressive-Like Disorder Induced by Reserpine Administration

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Ri Kim ◽  
Bo-Kyung Park ◽  
Chang-Seob Seo ◽  
No Soo Kim ◽  
Mi Young Lee
Keyword(s):  
Mouse Model ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Stress Hormones ◽  
Stem Bark ◽  
Plasma Corticosterone ◽  
Camp Response Element Binding ◽  
Bark Extract ◽  
Mrna Levels ◽  
Behavioral Experiments ◽  
Element Binding Protein

There is an urgent need to find antidepressants that can be administered for long periods without inducing severe side effects to replace conventional antidepressants that control monoamine levels, such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRI). We sought to determine the antidepressant effects of Fraxinus rhynchophylla Hance (F. rhynchophylla Hance, FX) and its components on a reserpine-induced mouse model. One hour after oral administration of FX (30, 50, and 100 mg/kg), esculin (50 mg/kg), esculetin (50 mg/kg), fraxin (50 mg/kg), and fluoxetine (20 mg/kg), reserpine was delivered intraperitoneally to mice. Behavioral experiments were conducted to measure anxiety and depressive-like behaviors after 10 days of administration. FX and its components increased the number of entries into the center of an open field as well as distance traveled within it and decreased immobility duration in the forced swim and tail suspension tests. Reserpine-induced increases in plasma corticosterone concentrations were attenuated by the administration of FX and its components, which were also found to decrease the reserpine-induced enhancement of mRNA levels of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor (TNF)-α, pro-inflammatory cytokines. Finally, the diminished expressions of hippocampal phosphorylated cAMP response element-binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) by reserpine were increased by FX and its components. Our results suggest that FX and its components regulate anxiety and depressive-like behaviors through stress hormones, immune regulation, and the activation of neuroprotective mechanisms, further supporting the potential of FX and its components as antidepressants.

scholarly journals Antidepressant-Like Effects of Gyejibokryeong-hwan in a Mouse Model of Reserpine-Induced Depression

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Bo-Kyung Park ◽  
Yu Ri Kim ◽  
Young Hwa Kim ◽  
Changsop Yang ◽  
Chang-Seob Seo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Forced Swim Test ◽  
Treatment Protocol ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Reserpine Treatment ◽  
Immobility Time ◽  
Element Binding Protein

Treatment with the antihypertensive agent reserpine depletes monoamine levels, resulting in depression. In the present study, we evaluated the antidepressant effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in a mouse model of reserpine-induced depression. Mice were treated with reserpine (0.5 mg·kg−1, i.p.) or phosphate-buffered saline (PBS, i.p., normal) once daily for 10 days. GBH (50, 100, 300, and 500 mg·kg−1), PBS (normal, control), fluoxetine (FXT, 20 mg·kg−1), or amitriptyline (AMT, 30 mg·kg−1) was administered orally 1 h prior to reserpine treatment. Mouse behavior was examined in the forced swim test (FST), tail suspension test (TST), and open-field test (OFT) following completion of the treatment protocol. Administration of GBH reduced immobility time in the FST and TST and significantly increased the total distance traveled in the OFT. Plasma serotonin levels were significantly lower in control mice than in normal mice, although these decreases were significantly attenuated to a similar extent by treatment with GBH, FXT, or AMT. Reserpine-induced increases in plasma corticosterone were also attenuated by GBH treatment. Moreover, GBH attenuated reserpine-induced increases in interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α mRNA expression in the hippocampus. In addition, GBH mice exhibited increased levels of brain-derived neurotrophic factor (BDNF) and a higher ratio of phosphorylated cAMP response element-binding protein (p-CREB) to CREB (p-CREB/CREB) in the hippocampus. Our results indicated that GBH can ameliorate depressive-like behaviors, affect the concentration of mood-related hormones, and help to regulate immune/endocrine dysfunction in mice with reserpine-induced depression, likely via activation of the BDNF-CREB pathway. Taken together, these findings indicate that GBH may be effective in treating patients with depression.

scholarly journals A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4892-4900 ◽  
Author(s):  
Courtney J. Rice ◽  
Curt A. Sandman ◽  
Mohammed R. Lenjavi ◽  
Tallie Z. Baram
Keyword(s):  
Mouse Model ◽  
Paraventricular Nucleus ◽  
Life Stress ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Early Life Stress ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Basal Plasma

Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models because these would enable use of powerful transgenic methods. Therefore, we have characterized a mouse model of chronic ES, which was provoked in mouse pups by abnormal, fragmented interactions with the dam. Dam-pup interaction was disrupted by limiting the nesting and bedding material in the cages, a manipulation that affected this parameter in a dose-dependent manner. At the end of their week-long rearing in the limited-nesting cages, mouse pups were stressed, as apparent from elevated basal plasma corticosterone levels. In addition, steady-state mRNA levels of CRH in the hypothalamic paraventricular nucleus of ES-experiencing pups were reduced, without significant change in mRNA levels of arginine vasopressin. Rearing mouse pups in this stress-provoking cage environment resulted in enduring effects: basal plasma corticosterone levels were still increased, and CRH mRNA levels in paraventricular nucleus remained reduced in adult ES mice, compared with those of controls. In addition, hippocampus-dependent learning and memory functions were impaired in 4- to 8-month-old ES mice. In summary, this novel, robust model of chronic early life stress in the mouse results in acute and enduring neuroendocrine and cognitive abnormalities. This model should facilitate the examination of the specific genes and molecules involved in the generation of this stress as well as in its consequences.

scholarly journals Involvement of Neuropeptide Y Y1 Receptors in the Regulation of Neuroendocrine Corticotropin-Releasing Hormone Neuronal Activity

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3666-3673 ◽  
Author(s):  
Eugene L. Dimitrov ◽  
M. Regina DeJoseph ◽  
Mark S. Brownfield ◽  
Janice H. Urban
Keyword(s):  
Neuropeptide Y ◽  
Hpa Axis ◽  
Binding Protein ◽  
Plasma Corticosterone ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Y1 Receptor ◽  
Element Binding Protein ◽  
Y1 Receptors

The neuroendocrine parvocellular CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus are the main integrators of neural inputs that initiate hypothalamic-pituitary-adrenal (HPA) axis activation. Neuropeptide Y (NPY) expression is prominent within the PVN, and previous reports indicated that NPY stimulates CRH mRNA levels. The purpose of these studies was to examine the participation of NPY receptors in HPA axis activation and determine whether neuroendocrine CRH neurons express NPY receptor immunoreactivity. Infusion of 0.5 nmol NPY into the third ventricle increased plasma corticosterone levels in conscious rats, with the peak of hormone levels occurring 30 min after injection. This increase was prevented by pretreatment with the Y1 receptor antagonist BIBP3226. Immunohistochemistry showed that CRH-immunoreactive neurons coexpressed Y1 receptor immunoreactivity (Y1r-ir) in the PVN, and a majority of these neurons (88.8%) were neuroendocrine as determined by ip injections of FluoroGold. Bilateral infusion of the Y1/Y5 agonist, [leu31pro34]NPY (110 pmol), into the PVN increased c-Fos and phosphorylated cAMP response element-binding protein expression and elevated plasma corticosterone levels. Increased expression of c-Fos and phosphorylated cAMP response element-binding protein was observed in populations of CRH/Y1r-ir cells. The current findings present a comprehensive study of NPY Y1 receptor distribution and activation with respect to CRH neurons in the PVN. The expression of NPY Y1r-ir by neuroendocrine CRH cells suggests that alterations in NPY release and subsequent activation of NPY Y1 receptors plays an important role in the regulation of the HPA.

scholarly journals Standardized Extract (HemoHIM) Protects against Scopolamine-Induced Amnesia in a Murine Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Seul-Ki Kim ◽  
Da-Ae Kwon ◽  
Yong Sang Kim ◽  
Hak Sung Lee ◽  
Hyun Kyu Kim ◽  
...  
Keyword(s):  
Murine Model ◽  
Memory Impairment ◽  
Therapeutic Potential ◽  
Muscarinic Acetylcholine Receptor ◽  
Camp Response Element Binding ◽  
Avoidance Task ◽  
Mrna Levels ◽  
Object Recognition Test ◽  
Y Maze ◽  
Element Binding Protein

HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) designed for immune regulation. In the present study, the memory-enhancing effects of a standardized extract (HemoHIM) on scopolamine-induced memory impairment in a murine model was investigated. To induce amnesia, scopolamine (1 mg/kg) was intraperitoneally (i.p.) injected into mice 30 min before the start of behavioral tests. The Y-maze, novel object recognition test (NORT), and passive avoidance task (PAT) were used to evoke memory functions. HemoHIM significantly improved scopolamine-induced memory impairment in ICR mice, which was evidenced by an improvement of spontaneous alternation in the Y-maze, recognition index in NORT, and latency time in PAT. To elucidate the possible mechanism, the cholinergic activity and mRNA levels of choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) were measured using reverse transcription (RT-PCR) and western blot analyses, respectively. HemoHIM treatment attenuated the scopolamine-induced hyperactivation of acetylcholinesterase (AchE) activity. In addition, ChAT, mAchR, and CREB mRNA levels were increased in the hippocampus compared with the scopolamine group. Furthermore, HemoHIM treatment resulted in elevated BDNF protein expression. These results indicate that HemoHIM may exert antiamnesic activity by increasing Ach and inhibiting AchE in the hippocampus. In addition, HemoHIM has therapeutic potential by upregulating ChAT, mAchR, and BDNF, which is apparently mediated by activation of the CREB and ERK signaling pathways.

scholarly journals Evaluation of anxiolytic and anti-depressant activity of Neolamarckia cadamba in mice

2021 ◽  
pp. 254-261
Author(s):  
Akwinder Kaur ◽  
Ajeet Pal Singh ◽  
Amar Pal Singh
Keyword(s):  
Drug Testing ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Objective Evaluation ◽  
Stem Bark ◽  
Oral Route ◽  
Bark Extract ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Stem Bark Extract ◽  
High Doses

Objective: Evaluation of anxiolytic and anti-depressant activity of Neolamarckia cadamba in mice. Material & Method: The aqueous and methanolic extract of “Neolamarckia cadamba” and chose low medium and high doses for therapy. The behavioral consequences of an oral acute or subacute (10 days) treatment. Neolamarckia cadamba (250 and 500 mg/kg, p.o) aqueous and methanolic stem bark extract assessed in male and female Swiss mice (EPM). Diazepam (1 mg/kg) will also be evaluated. Anti-anxiety drug testing in the lab. Results: Neolamarckia cadamba,  acute oral toxicity was detected with different extracts (ENC & AQNC) having dose  (5, 50, 300, 1000 mg/kg ) via the oral route,  shows no change in behavioral responses and observation shows no acute oral toxicity. Hence depending upon it, Dose was selected 250 mg/kg & 500 mg/kg for our experimental work. Conclusion: Neolamarckia cadamba has both anxiolytic and antidepressant properties, which likely operate through BZD receptors, selective serotonin reuptake inhibitors. The antidepressant and anxiolytic properties of Neolamarckia cadamba ethanolic and aqueous extracts were investigated in Swiss albino mice at doses of 250 and 500 mg/kg, respectively. Both extracts (ANC & ENC) showed strong antidepressant and anxiolytic efficacy using TST and EPM parameters.

scholarly journals Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Soichiro Seno ◽  
Satoshi Tomura ◽  
Hiromi Miyazaki ◽  
Shunichi Sato ◽  
Daizoh Saitoh
Keyword(s):  
Shock Wave ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Wave Model ◽  
Camp Response Element Binding ◽  
Hippocampal Neurogenesis ◽  
Selective Serotonin ◽  
Vehicle Group ◽  
Element Binding Protein

Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depression-like behavior induced by mild bTBI. Animals were divided into three groups: sham, LISW-Vehicle, and LISW-SSRI. LISW was applied to the head of anesthetized mice at 0.5 J/cm2. Twenty-eight days after the LISW, mice in the LISW-SSRI group exhibited reduced depression-like behavior, a significant increase in the number of cells co-stained for 5-bromo-2'-deoxyuridine (Brd-U) and doublecortin (DCX) in the dentate gyrus (DG) as well as increased brain-derived neurotrophic factor (BDNF) and serotonin levels in the hippocampus compared to the sham and LISW-Vehicle groups. Additionally, levels of phosphorylated cAMP response element binding protein (pCREB) in the DG were significantly decreased in the LISW-Vehicle group compared to that in the sham group. Importantly, pCREB levels were not significantly different between LISW-SSRI and sham groups suggesting that SSRI treatment may limit the downregulation of pCREB induced by mild bTBI. In conclusion, recovery from depression-like behavior after mild bTBI may be mediated by hippocampal neurogenesis induced by increased BDNF and serotonin levels as well as the inhibition of pCREB downregulation in the hippocampus.

Differential regulation of functional responses by β-adrenergic receptor subtypes in brown adipocytes

1999 ◽  
Vol 277 (1) ◽  
pp. R147-R153 ◽  
Author(s):  
Archana Chaudhry ◽  
James G. Granneman
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Camp Response Element Binding ◽  
Brown Adipocyte ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Functional Responses ◽  
Camp Response Element ◽  
Brown Adipose ◽  
Element Binding Protein

Brown adipose tissue contains both β1- and β3-adrenergic receptors (β-ARs), and whereas both receptor subtypes can activate adenylyl cyclase, recent studies suggest that these subtypes have different pharmacological properties and may serve different signaling functions. In this study, primary brown adipocyte cultures were used to determine the role of β-AR subtypes in mediating lipolysis and uncoupling protein-1 (UCP1) gene expression, elicited by the physiological neurohormone norepinephrine (NE). NE increased both lipolysis and UCP1 mRNA levels in brown adipocyte cultures; the β1-receptor-selective antagonist CGP-20712A strongly antagonized the increase in UCP1 gene expression but had little effect on lipolysis. The β3-receptor-selective agonist CL-316243 (CL) also increased lipolysis and UCP1 mRNA levels, yet CL was more potent in stimulating lipolysis than UCP1 gene expression. NE also increased the phosphorylation of cAMP response element-binding protein (CREB) and perilipin (PL), both of which are protein kinase A substrates that are differentially targeted to the nucleus and lipid droplets, respectively. β1-receptor blockade inhibited NE-stimulated phosphorylation of CREB but not PL. The results suggest that β-AR subtypes regulate different physiological responses stimulated by NE in brown adipocyte cultures in part by differentially transducing signals to subcellular compartments.

scholarly journals Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U

2010 ◽  
Vol 207 (8) ◽  
pp. 1661-1673 ◽  
Author(s):  
Kuen-Jer Tsai ◽  
Chun-Hung Yang ◽  
Yen-Hsin Fang ◽  
Kuan-Hung Cho ◽  
Wei-Lin Chien ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rna Binding ◽  
Camp Response Element Binding ◽  
Motor Dysfunction ◽  
Major Constituent ◽  
Dependent Manner ◽  
Motor Impairments ◽  
Cytoplasmic Inclusions ◽  
Element Binding Protein ◽  
Elevated Expression

TDP-43 is a multifunctional DNA/RNA-binding factor that has been implicated in the regulation of neuronal plasticity. TDP-43 has also been identified as the major constituent of the neuronal cytoplasmic inclusions (NCIs) that are characteristic of a range of neurodegenerative diseases, including the frontotemporal lobar degeneration with ubiquitin+ inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). We have generated a FTLD-U mouse model (CaMKII-TDP-43 Tg) in which TDP-43 is transgenically overexpressed in the forebrain resulting in phenotypic characteristics mimicking those of FTLD-U. In particular, the transgenic (Tg) mice exhibit impaired learning/memory, progressive motor dysfunction, and hippocampal atrophy. The cognitive and motor impairments are accompanied by reduced levels of the neuronal regulators phospho–extracellular signal-regulated kinase and phosphorylated cAMP response element-binding protein and increased levels of gliosis in the brains of the Tg mice. Moreover, cells with TDP-43+, ubiquitin+ NCIs and TDP-43–deleted nuclei appear in the Tg mouse brains in an age-dependent manner. Our data provide direct evidence that increased levels of TDP-43 protein in the forebrain is sufficient to lead to the formation of TDP-43+, ubiquitin+ NCIs and neurodegeneration. This FTLD-U mouse model should be valuable for the mechanistic analysis of the role of TDP-43 in the pathogenesis of FTLD-U and for the design of effective therapeutic approaches of the disease.

scholarly journals Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages

2012 ◽  
Vol 443 (2) ◽  
pp. 451-461 ◽  
Author(s):  
Manuel D. Díaz-Muñoz ◽  
Inés C. Osma-García ◽  
Manuel Fresno ◽  
Miguel A. Iñiguez
Keyword(s):  
Transcriptional Activation ◽  
Specific Binding ◽  
Camp Response Element Binding ◽  
Signalling Pathway ◽  
Mrna Levels ◽  
Activated Macrophages ◽  
Camp Signalling ◽  
Element Binding Protein ◽  
Cox 2 ◽  
Ep2 Receptor

PG (prostaglandin) E2 plays an important role in the modulation of the immune response and the inflammatory process. In the present study, we describe a PGE2 positive feedback for COX (cyclo-oxygenase)-2 and mPGES-1 [microsomal PGES (PGE synthase)-1] expression in the macrophage cell line RAW 264.7. Our results show that PGE2 induces COX-2 and mPGES-1 expression, an effect mimicked by dbcAMP (dibutyryl-cAMP) or forskolin. Furthermore, the cAMP signalling pathway co-operates with LPS (lipopolysaccharide) in the induction of COX-2 and mPGES-1 transcriptional activation. Analysis of the involvement of PGE receptors [EPs (E-prostanoids)] showed that incubation with EP2 agonists up-regulated both COX2 and mPGES-1 mRNA levels. Moreover, EP2 receptor overexpression enhanced the transcriptional activation of COX2 and mPGES-1 promoters. This induction was repressed by the PKA (protein kinase A) inhibitor H89. Activation of the PGE2/EP2/PKA signalling pathway induced the phosphorylation of CREB [CRE (cAMP-response element)-binding protein] in macrophages and stimulated the specific binding of this transcription factor to COX2 and mPGES-1 promoters. Deletion or mutation of potential CRE sites in both promoters diminished their transcriptional activity. In summary, the results of the present study demonstrate that activation of PKA/CREB signalling through the EP2 receptor by PGE2 plays a key role in the expression of COX-2 and mPGES-1 in activated macrophages.

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