scholarly journals M2-AChR Mediates Rapid Antidepressant-Like Effects of Scopolamine Through Activating the mTORC1-BDNF

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Liu ◽  
Dandan Shi ◽  
Zuoli Sun ◽  
Yi He ◽  
Jian Yang ◽  
...  
Keyword(s):  
Western Blotting ◽  
Open Field Test ◽  
Forced Swim Test ◽  
Muscarinic Acetylcholine Receptor ◽  
Cholinergic Receptor ◽  
Therapeutic Effects ◽  
Antidepressant Effects ◽  
Mtorc1 Signaling ◽  
Underlying Mechanisms

Background: Scopolamine, a non-selective muscarinic acetylcholine receptor (M1~5-AChR) antagonist, has rapid and robust antidepressant effects in humans and other species. However, which of the five M-AChRs mediates these therapeutic effects has not been fully identified. Several studies implicate M2-AChR as a potential antidepressant target of scopolamine. This study aimed to explore the role of M2-AChR in scopolamine's antidepressant-like effects and determine the underlying mechanisms.Methods: We used the classic novelty suppressed feeding test (NSFT), open field test (OFT) and forced swim test (FST) to observe antidepressant-related behaviors of normal rats, medial prefrontal cortex (mPFC) neuron silenced rats and M2-AChR knockdown rats treated with scopolamine. In a further experiment, the M2 cholinergic receptor antagonist methoctramine (MCT) was injected intracerebroventricularly into normal rats. Levels of mTORC1 and brain-derived neurotrophic factor (BDNF) in the mPFC of animals were analyzed by Western blotting.Results: Consistent with previous studies, mPFC was required for the antidepressant-like effects of scopolamine, and intracerebroventricular injection of MCT into rats could produce similar antidepressant-like effects. Use of AAV-shRNA to knock down M2-AChR in the mPFC resulted in the antidepressant-like effects of scopolamine being blunted. Furthermore, Western blotting demonstrated increased expression of mTORC1 signaling and BDNF in MCT-treated rats.Conclusion: Our results indicate that M2-AChR in the mPFC mediates the antidepressant-like effects of scopolamine by increasing the expression of BDNF and activating the mTORC1 signaling pathway.

scholarly journals Lifestyle Modification for Enhancing Autonomic Cardiac Regulation in Children: The Role of Exercise

Children ◽  
2019 ◽  
Vol 6 (11) ◽  
pp. 127
Author(s):  
Kathryn E Speer ◽  
Nenad Naumovski ◽  
Stuart Semple ◽  
Andrew J McKune
Keyword(s):  
Exercise Prescription ◽  
Lifestyle Modification ◽  
Exercise Duration ◽  
Population Characteristics ◽  
Cardiometabolic Health ◽  
Therapeutic Effects ◽  
Global Concern ◽  
Underlying Mechanisms ◽  
Autonomic Cardiac Regulation

Decreased physical activity (PA) is a global concern contributing to the rise in cardiometabolic diseases. One potential mechanism linking insufficient PA and poor health is dysregulated autonomic nervous system (ANS) activity. This relationship is established in adults and PA recommendations, with specific exercise prescription guidelines, have been proposed to overcome this societal health burden. However, research on the benefits and underlying mechanisms of exercise on ANS activity in children <18 years old is limited. This review aimed to describe the optimal exercise “dose” and potential mechanisms of action that exercise may pose on enhancing child ANS activity, represented by heart rate variability (HRV). PubMed, Web of Science and Google Scholar were searched for articles examining the influence of exercise on child HRV. Various exercise duration and frequency combinations appear to improve HRV indices, primarily those representing parasympathetic influence. Furthermore, both aerobic and resistance training benefit HRV through potentially different mechanisms with intensity proposed to be important for exercise prescription. Findings indicate that exercise is a crucial lifestyle modification with protective and therapeutic effects on cardiometabolic health associated with improvements in child ANS activity. Exercise programming must consider the various components including mode, intensity and population characteristics to optimize ANS health.

Geniposide Enhances Macrophage Autophagy through Downregulation of TREM2 in Atherosclerosis

2020 ◽  
Vol 48 (08) ◽  
pp. 1821-1840
Author(s):  
Yu-Ling Xu ◽  
Xiao-Yu Liu ◽  
Sai-Bo Cheng ◽  
Pei-Kun He ◽  
Mu-Keng Hong ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Myeloid Cell ◽  
Mtor Signaling ◽  
Therapeutic Effects ◽  
High Fat ◽  
Raw264.7 Macrophages ◽  
Key Factor ◽  
Underlying Mechanisms ◽  
Progression Of Atherosclerosis

Macrophage autophagy defect is closely related to the progression of atherosclerosis (AS) and is regulated by the triggering receptor expressed on myeloid cell 2 (TREM2). TREM2 is a key factor in the development of Alzheimer’s disease (AD), the deficiency of which leads to anomalous autophagy in microglia. However, the role of TREM2 in the autophagy of plaque macrophages is still unclear. Geniposide (GP) can inhibit AS progression and enhance macrophage autophagy, although the underlying mechanisms remain unknown. We found that high-fat diet (HFD) feeding significantly increased TREM2 levels and inhibited autophagy in the macrophages of ApoE[Formula: see text] mice. TREM2 overexpression in RAW264.7 macrophages decreased autophagy via activation of mTOR signaling. GP inhibited the progression of AS in ApoE[Formula: see text] mice, reinforced macrophage autophagy, and downregulated TREM2 by inhibiting mTOR signaling. Taken together, augmenting the autophagy levels in plaque macrophages by inhibiting the TREM2/mTOR axis can potentially impede atherosclerotic progression. The promising therapeutic effects of GP seen in this study should be validated in future trials, and the underlying mechanisms have to be elucidated in greater detail.

scholarly journals Evaluation of antidepressant effects of hydroalcoholic extract of Kelussia odoratissima Mozaffarian in male mice

2021 ◽  
Vol 23 (1) ◽  
pp. 44-50
Author(s):  
Najmeh Asgharzadeh ◽  
Fatemeh Hajihasani ◽  
Zahra Lorigooini ◽  
Marzieh Mardani ◽  
Hossein Amini Khoei ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Open Field ◽  
Field Test ◽  
Open Field Test ◽  
Forced Swim Test ◽  
Male Mice ◽  
Hydroalcoholic Extract ◽  
Swim Test ◽  
Forced Swim ◽  
Antidepressant Effects

Background and aims: Depression is one of the most common psychiatric disorders with serious impacts on individuals, and is often associated with physiological symptoms. In this study, we investigated the antidepressant effects of Kelussia odoratissima Mozaffarian extract in male mice. Methods: A total of 56 male mice (weight: 25-35 g; age: 6-8 weeks) were used. K. odoratissima Mozaffarian hydroalcoholic extract was prepared by maceration method. The forced swim test, open field test, and splash test were used to investigate the antidepressant effects. The mice were assigned into eight equal groups (n=7 each) as follows: receiving 25, 50, 75, and 100 mg/kg of K. odoratissima Mozaffarian extract; receiving 5 mg/kg reserpine; receiving 5 mg/kg reserpine along with 20 mg fluoxetine; and normal saline. All injections were done intraperitoneally for one week before the test. Malondialdehyde (MDA) levels and antioxidant capacity of serum and brain were also measured in all groups. Statistical analysis was performed by one-way ANOVA and Tukey’s test. Results: Extract of K. odoratissima Mozaffarian significantly decreased the immobility time in forced swim test (P<0.001). The extract also significantly increased splash time and elapsed time in the open field test, which was statistically significant compared with reserpinated mice (P<0.001). Reserpine increased MDA levels and decreased the antioxidant capacity of serum and brain, whereas hydroalcoholic extract of K. odoratissima decreased MDA dose-dependently and increased antioxidant capacity (P<0.001). Conclusion: The results of this study showed that hydroalcoholic extract of K. odoratissima has antidepressant effects, but further studies are necessary to investigate the involved mechanisms.

Response Interference as a Mechanism Underlying Implicit Measures

2008 ◽  
Vol 24 (4) ◽  
pp. 218-225 ◽  
Author(s):  
Bertram Gawronski ◽  
Roland Deutsch ◽  
Etienne P. LeBel ◽  
Kurt R. Peters
Keyword(s):  
Task Performance ◽  
Psychological Research ◽  
Implicit Measures ◽  
Mediation Model ◽  
Response Interference ◽  
Relevant Evidence ◽  
Moderated Mediation Model ◽  
Stimulus Features ◽  
Underlying Mechanisms

Over the last decade, implicit measures of mental associations (e.g., Implicit Association Test, sequential priming) have become increasingly popular in many areas of psychological research. Even though successful applications provide preliminary support for the validity of these measures, their underlying mechanisms are still controversial. The present article addresses the role of a particular mechanism that is hypothesized to mediate the influence of activated associations on task performance in many implicit measures: response interference (RI). Based on a review of relevant evidence, we argue that RI effects in implicit measures depend on participants’ attention to association-relevant stimulus features, which in turn can influence the reliability and the construct validity of these measures. Drawing on a moderated-mediation model (MMM) of task performance in RI paradigms, we provide several suggestions on how to address these problems in research using implicit measures.

The More You Say, the Less They Hear

2015 ◽  
Vol 27 (4) ◽  
pp. 159-169 ◽  
Author(s):  
Elsbeth D. Asbeek Brusse ◽  
Marieke L. Fransen ◽  
Edith G. Smit
Keyword(s):  
Hearing Protection ◽  
Entertainment Education ◽  
Mediating Role ◽  
Attitude Measures ◽  
Underlying Mechanisms

Abstract. This study examined the effects of disclosure messages in entertainment-education (E-E) on attitudes toward hearing protection and attitude toward the source. In addition, the (mediating) role of the underlying mechanisms (i.e., transportation, identification, and counterarguing) was studied. In an experiment (N = 336), three different disclosure messages were compared with a no-disclosure condition. The results show that more explicit disclosure messages negatively affect transportation and identification and stimulate the generation of counterarguments. In addition, the more explicit disclosure messages affect both attitude measures via two of these processes (i.e., transportation and counterarguing). Less explicit disclosure messages do not have this effect. Implications of the findings are discussed.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

Inflammatory Biomarkers in Atrial Fibrillation

2019 ◽  
Vol 26 (5) ◽  
pp. 837-854 ◽  
Author(s):  
Effimia Zacharia ◽  
Nikolaos Papageorgiou ◽  
Adam Ioannou ◽  
Gerasimos Siasos ◽  
Spyridon Papaioannou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Large Scale ◽  
Inflammatory Biomarkers ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

Inter-Tissue and Intra-Tissue Co-Expression Networks in Human Metabolism: Morphological Evaluation of the Link Between Transcription Factors ERβ and NFAT in Morbid Obesity

2020 ◽  
Vol 17 (1) ◽  
pp. 63-80
Author(s):  
Athina Chasapi ◽  
Kostas Balampanis ◽  
Eleni Kourea ◽  
Fotios Kalfaretzos ◽  
Vaia Lambadiari ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Adipose Tissue ◽  
Clinicopathological Parameters ◽  
Morbidly Obese ◽  
Human Metabolism ◽  
Activated T Cells ◽  
Alcoholic Fatty Liver ◽  
Morphological Evaluation ◽  
Underlying Mechanisms

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive “cross-talk” with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2). Introduction: Our study is an “in situ” morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored. The aim of the present study was to determine the role of ERβ and NFAT in the underlying pathophysiology of obesity and related comorbidities. We have investigated the expression of specific proteins using immunochemistry methodologies. Methods: Our population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver and the differential protein expression was evaluated by immunohistochemistry. Results: We demonstrated an extensive intra- and inter-tissue co-expression network, which confirms the tissue-specific and integral role of each one of the investigated proteins in morbid obesity. Moreover, a beneficial role of ERβ and NFATc1 against NAFLD is implicated, whereas the distinct roles of TIF2 still remain an enigma. Conclusions: We believe that our findings will shed light on the complex underlying mechanisms and that the investigated biomarkers could represent future targets for the prevention and therapy of obesity and its comorbidities.

scholarly journals GPER-Deficient Rats Exhibit Lower Serum Corticosterone Level and Increased Anxiety-Like Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-22 ◽  
Author(s):  
Yi Zheng ◽  
Meimei Wu ◽  
Ting Gao ◽  
Li Meng ◽  
Xiaowei Ding ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Corticosterone Level ◽  
Brain Structures ◽  
Ample Evidence ◽  
Genetic Ablation ◽  
Serum Corticosterone ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
Prolonged Stress

Ample evidence suggests that estrogens have strong influences on the occurrence of stress-related mood disorders, but the underlying mechanisms remain poorly understood. Through multiple approaches, we demonstrate that the G protein-coupled estrogen receptor (GPER) is widely distributed along the HPA axis and in brain structures critically involved in mood control. Genetic ablation of GPER in the rat resulted in significantly lower basal serum corticosterone level but enhanced ACTH release in response to acute restraint stress, especially in the female. GPER-/- rats of either sex displayed increased anxiety-like behaviors and deficits in learning and memory. Additionally, GPER deficiency led to aggravation of anxiety-like behaviors following single-prolonged stress (SPS). SPS caused significant decreases in serum corticosterone in WT but not in GPER-deficient rats. The results highlight an important role of GPER at multiple sites in regulation of the HPA axis and mood.

scholarly journals 306 - Loneliness and mortality in older adults and the role of depression

2020 ◽  
Vol 32 (S1) ◽  
pp. 64-64
Author(s):  
T.J. Holwerda ◽  
D. Rhebergen ◽  
H.C. Comijs ◽  
J.J.M. Dekker ◽  
M.L. Stek
Keyword(s):  
Cardiovascular Disease ◽  
Older Adults ◽  
Mortality Risk ◽  
Meta Analysis ◽  
Clinical Perspective ◽  
Cross Sectional ◽  
Mediating Role ◽  
Underlying Mechanisms ◽  
Dexamethasone Suppression

Background:The prevalence of loneliness increases with age. The presence of loneliness in older adults has been found to be associated with health problems such as depression, decreased cognitive functioning, increases in systolic blood pressure and increased mortality. The underlying mechanisms of the higher mortality risk are largely unknown.Methods:Meta-analysis to investigate the present evidence for the associations between loneliness and mortality. Cross-sectional studies investigating the associations between loneliness and cardiovascular disease and between loneliness and cortisol in 378 depressed and 132 non-depressed older adults.Results:Loneliness appears to be associated with increased mortality, although when only studies are included that consider depression as a covariate, the association is not significant. Therefore it seems likely that depression plays a mediating role in the higher mortality risk.We did not find a significant association between loneliness and cardiovascular disease. In contrast, loneliness was significantly associated with lower cortisol output and decreased dexamethasone suppression.Discussion:The results and their implications for prevention and treatment will be discussed from a clinical perspective as well as a general health perspective. Is loneliness as potentially dangerous as depression?

Sign in / Sign up

Export Citation Format

Share Document