scholarly journals Neurobiology of panic and pH chemosensation in the brain

2011 ◽  
Vol 13 (4) ◽  
pp. 475-483 ◽  
Keyword(s):  
Animal Models ◽  
Panic Disorder ◽  
Ph Regulation ◽  
Ph Sensitive ◽  
Panic Attacks ◽  
Brain Ph ◽  
Neuron Function ◽  
Lactate Infusion ◽  
The Brain ◽  
Insight Into

Panic disorder is a common and disabling illness for which treatments are too frequently ineffective. Greater knowledge of the underlying biology could aid the discovery of better therapies. Although panic attacks occur unpredictably, the ability to provoke them in the laboratory with challenge protocols provides an opportunity for crucial insight into the neurobiology of panic. Two of the most well-studied panic provocation challenges are CO(2) inhalation and lactate infusion. Although it remains unclear how these challenges provoke panic animal models of CO(2) and lactate action are beginning to emerge, and offer unprecedented opportunities to probe the molecules and circuits underlying panic attacks. Both CO(2) and lactate alter pH balance and may generate acidosis that can influence neuron function through a growing list of pH-sensitive receptors. These observations suggest that a key to better understanding of panic disorder may He in more knowledge of brain pH regulation and pH-sensitive receptors.

scholarly journals How to Improve the Antioxidant Defense in Asphyxiated Newborns—Lessons from Animal Models

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 898
Author(s):  
Hanna Kletkiewicz ◽  
Maciej Klimiuk ◽  
Alina Woźniak ◽  
Celestyna Mila-Kierzenkowska ◽  
Karol Dokladny ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Animal Models ◽  
Iron Chelation ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Protective Capacity ◽  
Neonatal Asphyxia ◽  
New Therapeutic Approaches ◽  
The Brain ◽  
Insight Into

Oxygen free radicals have been implicated in brain damage after neonatal asphyxia. In the early phase of asphyxia/reoxygenation, changes in antioxidant enzyme activity play a pivotal role in switching on and off the cascade of events that can kill the neurons. Hypoxia/ischemia (H/I) forces the brain to activate endogenous mechanisms (e.g., antioxidant enzymes) to compensate for the lost or broken neural circuits. It is important to evaluate therapies to enhance the self-protective capacity of the brain. In animal models, decreased body temperature during neonatal asphyxia has been shown to increase cerebral antioxidant capacity. However, in preterm or severely asphyxiated newborns this therapy, rather than beneficial seems to be harmful. Thus, seeking new therapeutic approaches to prevent anoxia-induced complications is crucial. Pharmacotherapy with deferoxamine (DFO) is commonly recognized as a beneficial regimen for H/I insult. DFO, via iron chelation, reduces oxidative stress. It also assures an optimal antioxidant protection minimizing depletion of the antioxidant enzymes as well as low molecular antioxidants. In the present review, some aspects of recently acquired insight into the therapeutic effects of hypothermia and DFO in promoting neuronal survival after H/I are discussed.

Abstract 213: Hematoma-infiltrating Macrophages Transition From Inflammatory to Reparative Programs in Patients After Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Michael H Askenase ◽  
Brittany A Goods ◽  
Arthur F Steinschneider ◽  
Khadir Raddassi ◽  
Hannah Beatty ◽  
...  
Keyword(s):  
Animal Models ◽  
Intracerebral Hemorrhage ◽  
Acid Metabolism ◽  
Transcriptional Analysis ◽  
Rna Seq ◽  
Mass Cytometry ◽  
Inflammatory Damage ◽  
Inflammatory Profile ◽  
The Brain ◽  
Insight Into

Intracerebral hemorrhage (ICH) causes rapid recruitment of circulating leukocytes to the injury; however, the roles of these cells in disease progression and repair in the brain are poorly understood. Findings from animal models have failed to translate into effective therapies for ICH, emphasizing the importance of studying the ICH immune response in the patient population. To gain insight into the inflammatory response in patient hematomas, we are utilizing mass cytometry, flow cytometry, and RNA-seq to characterize hematoma-infiltrating leukocytes isolated from ICH patients over a 5 day period, in conjunction with the ongoing MISTIE III trial for surgical evacuation of ICH. We have found that the hematoma immune infiltrate is predominantly composed of neutrophils and macrophages recruited from the circulation, rather than CNS-resident microglia. We have observed that hematoma macrophages have acquired a distinct phenotype differing from phagocyte populations in the peripheral blood, suggesting that their gene expression is controlled by local signals in the hematoma. Preliminary transcriptional analysis of hematoma macrophages 24-50 hours post-ICH has revealed an inflammatory profile characterized by increased expression of antigen presentation, TLR signaling, glycolytic metabolism, and prostaglandin production pathways (Figure 1). Intriguingly, by 100 hours post-ICH, macrophages downregulated these pathways and engaged a wound healing program characterized by TGF-beta signaling, fatty acid metabolism, and collagen deposition (Figure 1). These findings, in agreement with our previous results in animal models of ICH, suggest that recruited macrophages may contribute not only to initial inflammatory damage, but also to clearance of the hematoma and resolution of inflammation, making them potentially ideal targets for therapeutic intervention.

Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis

2021 ◽  
Author(s):  
Umit Tural ◽  
Dan V. Iosifescu
Keyword(s):  
Carbon Dioxide ◽  
Meta Analysis ◽  
Provocation Test ◽  
Sodium Lactate ◽  
Panic Attacks ◽  
Provocation Tests ◽  
Inhalation Challenge ◽  
Carbon Dioxide Co2 ◽  
Lactate Infusion ◽  
The Brain

Abstract Background Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods. Methods Odds ratios were calculated for each of the original studies and were pooled using the random-effects model. Results Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48–40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88–14.21). Conclusion The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.

scholarly journals Cholecystokinin and Panic Disorder: Reflections on the History and Some Unsolved Questions

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5657
Author(s):  
Jens F. Rehfeld
Keyword(s):  
Panic Disorder ◽  
Panic Attacks ◽  
Normal Brain ◽  
Brain Functions ◽  
Gut Hormone ◽  
Neuropsychiatric Diseases ◽  
The Common ◽  
Almost All ◽  
The Brain ◽  
Cck2 Receptor

The classic gut hormone cholecystokinin (CCK) and its CCK2-receptor are expressed in almost all regions of the brain. This widespread expression makes CCK by far the most abundant peptidergic transmitter system in the brain. This CNS-ubiquity has, however, complicated the delineation of the roles of CCK peptides in normal brain functions and neuropsychiatric diseases. Nevertheless, the common panic disorder disease is apparently associated with CCK in the brain. Thus, the C-terminal tetrapeptide fragment of CCK (CCK-4) induces, by intravenous administration in a dose-related manner, panic attacks that are similar to the endogenous attacks in panic disorder patients. This review describes the history behind the discovery of the panicogenic effect of CCK-4. Subsequently, the review discusses three unsettled questions about the involvement of cerebral CCK in the pathogenesis of anxiety and panic disorder, including therapeutic attempts with CCK2-receptor antagonists.

The Neurobiology of Panic Disorder: Toward an Integrated Model

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S12) ◽  
pp. 12-24 ◽  
Author(s):  
Dan J. Stein
Keyword(s):  
Panic Disorder ◽  
Treatment Strategies ◽  
Integrated Model ◽  
Additional Treatment ◽  
Panic Attacks ◽  
Imaging Studies ◽  
Anticipatory Anxiety ◽  
Fear And Anxiety ◽  
Insight Into ◽  
Neuroimaging Techniques

AbstractPanic disorder (PD) is a complex, multidimensional psychiatric disorder characterized by the presence of panic attacks as well as anticipatory anxiety and panic-related phobias (eg, agoraphobia). Although the etiology of this disabling disorder remains unclear, advances in basic neuroscience and in imaging studies have led to a greater understanding of the neurocircuitry and neurochemistry that are involved in modulating fear and anxiety and that are relevant to understanding PD. A preliminary integrated model can be outlined, but there is a need for additional research that cuts across genetic investigation, provocation studies, neuroimaging techniques, and treatment trials. As research continues and greater insight into the mechanisms underlying PD is achieved, additional treatment strategies may emerge.

scholarly journals Systematic analysis of brain lactate and pH levels in 65 animal models related to neuropsychiatric conditions

2021 ◽  
Author(s):  
Hideo Hagihara ◽  
Hirotaka Shoji ◽  
Tsuyoshi Miyakawa ◽  
Keyword(s):  
Working Memory ◽  
Energy Metabolism ◽  
Animal Models ◽  
Negative Correlation ◽  
Confounding Factors ◽  
Brain Ph ◽  
Lactate Levels ◽  
The Brain ◽  
Brain Energy ◽  
Brain Lactate

AbstractAltered brain energy metabolism associated with increase in lactate levels and the resultant decrease in pH have been increasingly implicated in multiple neuropsychiatric disorders, such as schizophrenia, bipolar disorder, autism spectrum disorder and neurodegenerative disorders. Although it is controversial, change of pH/ lactate level as a primary feature of these diseases, rather than a result of confounding factors such as medication and agonal state, has been evidenced. Animal models that can be studied without such confounding factors inherent to humans are a suitable alternative to understand the controversy. However, the knowledge in animal models regarding brain pH and lactate and their relation to behavioral outcomes is limited in the context of neuropsychiatric disease conditions. In this study, we investigated the common occurrence of changes in the pH and lactate levels in the brain in animal models by analyzing 65 animal models related to neuropsychiatric and neurodegenerative diseases with 1,239 animals. Additionally, we evaluated the behavioral phenotypes relative to the chemical changes in the brain. Among the models, 27 and 24 had significant changes in brain pH and lactate levels, respectively, including Shank2 KO mice, Clock mutant mice, serotonin transporter KO mice, mice with a paternal duplication of human chromosome 15q11-13, Fmr1 KO mice, BTBR mice, APP-J20 Tg mice, social defeat stress-exposed mice, corticosterone-treated mice, and streptozotocin-induced diabetic mice. Meta-analysis of the data revealed a highly significant negative correlation between brain pH and lactate levels, suggestive of increased lactate levels causing decreased brain pH. Statistical learning algorithm based on the comprehensive data has revealed that the increased brain lactate levels can be predominantly predicted by the indices for the percentage of correct response in working memory test, with a significant simple, negative correlation. Our results suggest that brain energy metabolism is commonly altered in many animal models of neuropsychiatric and neurodegenerative diseases, which may be associated with working memory performance. We consider our study to be an essential step suggesting that the brain endophenotypes serve as a basis for the transdiagnostic characterization of the biologically heterogeneous and debilitating cognitive illnesses. Based on these results, we are openly accepting collaborations to extend these findings and to test the hypotheses generated in this study using more animal models. We welcome any mice/rat models of diseases with or without any behavioral phenotypes.

Animal models of alcohol use disorder and the brain: From casual drinking to dependence.

2019 ◽  
Vol 5 (3) ◽  
pp. 222-242 ◽  
Author(s):  
Nicole A. Crowley ◽  
Nigel C. Dao ◽  
Sarah N. Magee ◽  
Alexandre J. Bourcier ◽  
Emily G. Lowery-Gionta
Keyword(s):  
Alcohol Use ◽  
Animal Models ◽  
Alcohol Use Disorder ◽  
The Brain

scholarly journals Is There a Brain Microbiome?

2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Ground Truth ◽  
Healthy Human ◽  
Strong Motivation ◽  
The Many ◽  
The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

scholarly journals Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats’ Brain and Heart

2021 ◽  
Vol 22 (13) ◽  
pp. 6839
Author(s):  
Ali H. El-Far ◽  
Yaser H. A. Elewa ◽  
Elsayeda-Zeinab A. Abdelfattah ◽  
Abdel-Wahab A. Alsenosy ◽  
Mustafa S. Atta ◽  
...  
Keyword(s):  
Animal Models ◽  
Calcium Binding ◽  
Caspase 3 ◽  
Combination Group ◽  
Preventive Effect ◽  
Group Data ◽  
Adapter Molecule ◽  
The Brain ◽  
Bcl2 Expression

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.

Effects of the SNAP25 on Integration Ability of Brain Functions in Children With ADHD

2020 ◽  
pp. 108705472096456
Author(s):  
Yue Yang ◽  
Gang Peng ◽  
Hongwu Zeng ◽  
Diangang Fang ◽  
Linlin Zhang ◽  
...  
Keyword(s):  
Time Window ◽  
Precentral Gyrus ◽  
Children With Adhd ◽  
Brain Functions ◽  
Lingual Gyrus ◽  
Window Method ◽  
Central Gyrus ◽  
The Right ◽  
The Brain ◽  
Insight Into

Objective: The present study aimed to examine the effects of SNAP25 on the integration ability of intrinsic brain functions in children with ADHD, and whether the integration ability was associated with working memory (WM). Methods: A sliding time window method was used to calculate the spatial and temporal concordance among five rs-fMRI regional indices in 55 children with ADHD and 20 healthy controls. Results: The SNAP25 exhibited significant interaction effects with ADHD diagnosis on the voxel-wise concordance in the right posterior central gyrus, fusiform gyrus and lingual gyrus. Specifically, for children with ADHD, G-carriers showed increased voxel-wise concordance in comparison to TT homozygotes in the right precentral gyrus, superior frontal gyrus, postcentral gyrus, and middle frontal gyrus. The voxel-wise concordance was also found to be related to WM. Conclusion: Our findings provided a new insight into the neural mechanisms of the brain function of ADHD children.

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