scholarly journals PEN Receptor GPR83 in Anxiety-Like Behaviors: Differential Regulation in Global vs Amygdalar Knockdown

2021 ◽  
Vol 15 ◽  
Author(s):  
Amanda K. Fakira ◽  
Lindsay M. Lueptow ◽  
Nikita A. Trimbake ◽  
Lakshmi A. Devi
Keyword(s):  
Anxiety Disorders ◽  
Stress Responses ◽  
Basolateral Amygdala ◽  
Treatment Options ◽  
The United States ◽  
Brain Regions ◽  
Receptor Expression ◽  
Minimal Impact ◽  
Female Mice ◽  
Receptor Targets

Anxiety disorders are prevalent across the United States and result in a large personal and societal burden. Currently, numerous therapeutic and pharmaceutical treatment options exist. However, drugs to classical receptor targets have shown limited efficacy and often come with unpleasant side effects, highlighting the need to identify novel targets involved in the etiology and treatment of anxiety disorders. GPR83, a recently deorphanized receptor activated by the abundant neuropeptide PEN, has also been identified as a glucocorticoid regulated receptor (and named GIR) suggesting that this receptor may be involved in stress-responses that underlie anxiety. Consistent with this, GPR83 null mice have been found to be resistant to stress-induced anxiety. However, studies examining the role of GPR83 within specific brain regions or potential sex differences have been lacking. In this study, we investigate anxiety-related behaviors in male and female mice with global knockout and following local GPR83 knockdown in female mice. We find that a global knockdown of GPR83 has minimal impact on anxiety-like behaviors in female mice and a decrease in anxiety-related behaviors in male mice. In contrast, a local GPR83 knockdown in the basolateral amygdala leads to more anxiety-related behaviors in female mice. Local GPR83 knockdown in the central amygdala or nucleus accumbens (NAc) showed no significant effect on anxiety-related behaviors. Finally, dexamethasone administration leads to a significant decrease in receptor expression in the amygdala and NAc of female mice. Together, our studies uncover a significant, but divergent role for GPR83 in different brain regions in the regulation of anxiety-related behaviors, which is furthermore dependent on sex.

scholarly journals Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Laurence Dion-Albert ◽  
Alice Cadoret ◽  
Ellen Doney ◽  
Fernanda Neutzling Kaufmann ◽  
Katarzyna A. Dudek ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Stress Responses ◽  
Social Stress ◽  
Depressive Disorders ◽  
Brain Regions ◽  
Brain Barrier ◽  
Female Mice ◽  
Blood Brain ◽  
Stressed Female ◽  
Soluble E Selectin

AbstractPrevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.

scholarly journals A REVIEW ON THE NEURAL CIRCUITS IN ANXIETY DISORDERS

2016 ◽  
Vol 9 (9) ◽  
pp. 26
Author(s):  
Ashwani Arya ◽  
Gulshan Sindhwani
Keyword(s):  
Anxiety Disorders ◽  
Behavioral Problems ◽  
Social Withdrawal ◽  
Treatment Options ◽  
Brain Regions ◽  
Emotional And Behavioral Problems ◽  
Diverse Range ◽  
Evidence Based Treatment ◽  
Reciprocal Connections

ABSTRACTAnxiety disorders are among the most common mental, emotional, and behavioral problems. These affect one-eighth of the total population worldwide.Anxiety disorders are a group of mental disorders characterized by irritability, fear, insomnia, nervousness, tachycardia, inability to concentrate,poor coping skills, palpitation, sweating, agoraphobia, and social withdrawal. Brain regions and networks involved in anxiety symptomatology isan effort to better understand the mechanism involved and to develop more effective treatments for the anxiety disorders. Thus, neuroanatomicaland neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and theprefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterationsin a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. The neurotransmitter like corticotropin-releasingfactor, neuropeptides (substance P, neuropeptide Y, oxytocin, orexin, and galanin) are implicated in anxiety pathways. Each of these active areas ofresearch holds promise for expanding and improving evidence-based treatment options for individuals suffering with clinical anxiety. Therefore,this article gives the information on the neurocognitive mechanisms, causes, neurotransmitter involved in anxiety disorders and emphasize on thetherapeutic targets for anxiety disorders.Keywords: Anxiety, Stress, Amygdala, Corticotropin releasing factor, Insula, Thalamus.

Pharmacotherapy of Anxiety Disorders

2013 ◽  
pp. 636-639
Author(s):  
James W. Murrough ◽  
Dan V. Iosifescu ◽  
Dennis S. Charney
Keyword(s):  
Anxiety Disorders ◽  
Treatment Options ◽  
The United States ◽  
Evidence Base ◽  
Current Evidence ◽  
Generalized Anxiety ◽  
Pharmacological Agents ◽  
Current Evidence Base ◽  
High Degree ◽  
Monoaminergic Agents

Anxiety disorders are among the most prevalent mental disorders in the United States and are associated with a high degree of morbidity and public health costs. This chapter will present a general approach to the diagnosis and treatment of these disorders and summarize the current evidence base for pharmacotherapeutic treatment options in individual disorders, including panic disorder, social phobia, posttraumatic stress disorder, generalized anxiety disorder.The serotonin-selective and serotonin norepinephrine reuptake inhibitors are generally considered first-line treatment while older monoaminergic agents are often efficacious but are limited by safety and tolerability issues. The benzodiazepines play an important role in the treatment of some anxiety disorders, however these agents also possess important limitations. Other pharmacological agents have a more limited evidence base. Continued progress in basic and translational neuroscience is expected to meet the need for new, more effective treatments for patients suffering from these disorders.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

Growth of prefrontal and limbic brain regions and anxiety disorders in children born very preterm

2021 ◽  
pp. 1-12
Author(s):  
Courtney P. Gilchrist ◽  
Deanne K. Thompson ◽  
Bonnie Alexander ◽  
Claire E. Kelly ◽  
Karli Treyvaud ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Anxiety Disorders ◽  
Orbitofrontal Cortex ◽  
Developmental Trajectories ◽  
Brain Regions ◽  
Social Risk ◽  
Intracranial Volume ◽  
Total Brain Volume ◽  
Very Preterm ◽  
The Right

Abstract Background Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years. Methods MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview. Results VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk. Conclusions Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.

scholarly journals Can quantifying morphology and TMEM119 expression distinguish between microglia and infiltrating macrophages after ischemic stroke and reperfusion in male and female mice?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kimberly F. Young ◽  
Rebeca Gardner ◽  
Victoria Sariana ◽  
Susan A. Whitman ◽  
Mitchell J. Bartlett ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Western Blot ◽  
Calcium Binding ◽  
Transmembrane Protein ◽  
Brain Regions ◽  
Morphological Data ◽  
Cell Populations ◽  
Male And Female ◽  
Female Mice

AbstractBackgroundIschemic stroke is an acquired brain injury with gender-dependent outcomes. A persistent obstacle in understanding the sex-specific neuroinflammatory contributions to ischemic brain injury is distinguishing between resident microglia and infiltrating macrophages—both phagocytes—and determining cell population-specific contributions to injury evolution and recovery processes. Our purpose was to identify microglial and macrophage populations regulated by ischemic stroke using morphology analysis and the presence of microglia transmembrane protein 119 (TMEM119). Second, we examined sex and menopause differences in microglia/macrophage cell populations after an ischemic stroke.MethodsMale and female, premenopausal and postmenopausal, mice underwent either 60 min of middle cerebral artery occlusion and 24 h of reperfusion or sham surgery. The accelerated ovarian failure model was used to model postmenopause. Brain tissue was collected to quantify the infarct area and for immunohistochemistry and western blot methods. Ionized calcium-binding adapter molecule, TMEM119, and confocal microscopy were used to analyze the microglia morphology and TMEM119 area in the ipsilateral brain regions. Western blot was used to quantify protein quantity.ResultsPost-stroke injury is increased in male and postmenopause female mice vs. premenopause female mice (p< 0.05) with differences primarily occurring in the caudal sections. After stroke, the microglia underwent a region, but not sex group, dependent transformation into less ramified cells (p< 0.0001). However, the number of phagocytic microglia was increased in distal ipsilateral regions of postmenopausal mice vs. the other sex groups (p< 0.05). The number of TMEM119-positive cells was decreased in proximity to the infarct (p< 0.0001) but without a sex group effect. Two key findings prevented distinguishing microglia from systemic macrophages. First, morphological data were not congruent with TMEM119 immunofluorescence data. Cells with severely decreased TMEM119 immunofluorescence were ramified, a distinguishing microglia characteristic. Second, whereas the TMEM119 immunofluorescence area decreased in proximity to the infarcted area, the TMEM119 protein quantity was unchanged in the ipsilateral hemisphere regions using western blot methods.ConclusionsOur findings suggest that TMEM119 is not a stable microglia marker in male and female mice in the context of ischemic stroke. Until TMEM119 function in the brain is elucidated, its use to distinguish between cell populations following brain injury with cell infiltration is cautioned.

scholarly journals The Public’s Perception of Interventions for Migraine Headache Disorders: A Crowdsourcing Population-Based Study

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Orr Shauly ◽  
Daniel J Gould ◽  
Ketan M Patel
Keyword(s):  
Migraine Headache ◽  
Treatment Options ◽  
The United States ◽  
Cost Of Care ◽  
Adverse Outcomes ◽  
Amazon Mechanical Turk ◽  
Cross Sectional ◽  
Economic Productivity ◽  
Migraine Headaches ◽  
Patient Reported

Abstract Background Migraine disorders are a leading cause of morbidity and decreased economic productivity in the United States among both men and women. As such, it is important to consider patient opinions, and have an accurate representation of the burden and sentiment toward currently available interventions among those suffering from migraines. Objectives The aim of the study was to assess patient options regarding adverse outcomes of the various treatment options available for migraine headaches. Methods A prospective cross-sectional study of volunteers recruited through an internet crowdsourcing service, Amazon Mechanical Turk©, was conducted. Surveys were administered to collect patient-reported opinions regarding adverse outcomes of both surgical and nonsurgical treatment options for migraine headaches. Results The prevalence of migraine headache across all study participants was 15.6% and varied slightly across participant demographics. Individuals ages 35–44 (2.73 migraines per month) experienced the fewest migraine and with the lowest severity. Those individuals ages 45+ experienced the most severe headaches (Visual Analog Scale = 44.23 mm). Additionally, the greatest migraine frequency and severity existed among those households with yearly income of $75,000–$100,000. The lowest injection therapy utility scores were obtained for adverse outcomes of hematoma (47.60 mm) and vertigo (54.40 mm). Conclusions Migraine headaches remains a significant problem among the US population, with an overall prevalence of 15.6% (approximately 50 million Americans). Additionally, physicians interesting in offering minimally invasive or surgical treatment for migraine headaches should focus on mitigating patient fears regarding clinical outcomes and cost of care.

scholarly journals Differential Expression of Pine and Cronartium quercuum f. sp. fusiforme Genes in Fusiform Rust Galls

2004 ◽  
Vol 70 (1) ◽  
pp. 441-451 ◽  
Author(s):  
Jaimie M. Warren ◽  
Sarah F. Covert
Keyword(s):  
Stress Responses ◽  
Axenic Culture ◽  
The United States ◽  
Northern Analysis ◽  
Pcr Analysis ◽  
Rust Disease ◽  
Fusiform Rust ◽  
Expression Levels ◽  
Cronartium Quercuum ◽  
Gene Expression Levels

ABSTRACT Cronartium quercuum f. sp. fusiforme is the causative agent of fusiform rust disease of southern pines in the United States. This disease is characterized by the formation of woody branch and stem galls. Differential display was used to identify pine genes whose expression is altered by C. quercuum f. sp. fusiforme infection and to identify C. quercuum f. sp. fusiforme genes that are expressed in fusiform rust galls. Six pine cDNAs that appeared to be differentially expressed in galled and healthy stems and 13 C. quercuum f. sp. fusiforme cDNAs expressed in galled tissues were identified. A probe that hybridizes specifically to C. quercuum f. sp. fusiforme 18S rRNA was used to estimate that 14% of the total RNA in fusiform rust galls was from C. quercuum f. sp. fusiforme. This finding was used to calibrate gene expression levels in galls when comparing them to expression levels in uninfected pines or in isolated C. quercuum f. sp. fusiforme cultures. According to Northern analysis and reverse transcriptase PCR analysis, all six of the pine clones were expressed at lower levels in galls than in healthy tissues. Seven of the nine C. quercuum f. sp. fusiforme clones that were assayed were expressed at higher levels in galls than in axenic culture. A number of the cDNAs encode proteins that are similar to those that play roles in plant development, plant defense, or fungal stress responses.

scholarly journals The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid-βProduction in Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Li Zuo ◽  
Benjamin T. Hemmelgarn ◽  
Chia-Chen Chuang ◽  
Thomas M. Best
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Treatment Options ◽  
Memory Loss ◽  
The United States ◽  
Traditional Medicines ◽  
Progressive Neurodegeneration ◽  
Antioxidant Supplements

An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer’s disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aβoverproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Aβplaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors.

Sign in / Sign up

Export Citation Format

Share Document