scholarly journals Mice Lacking GABAA Receptor δ Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs

2021 ◽  
Vol 12 ◽  
Author(s):  
Milo Grotell ◽  
Shamsiiat Abdurakhmanova ◽  
Lauri V. Elsilä ◽  
Esa R. Korpi
Keyword(s):  
Drug Effects ◽  
Chloride Ion ◽  
Positive Control ◽  
Wild Type ◽  
Drug Induced ◽  
Brain Functions ◽  
Drug Classes ◽  
Specific Antagonist ◽  
Multiple Drugs ◽  
The Brain

In the brain, extrasynaptically expressed ionotropic, δ subunit-containing γ-aminobutyric acid A-type receptors (δ-GABAARs) have been implicated in drug effects at both neuronal and behavioral levels. These alterations are supposed to be caused via drug-induced modulation of receptor ionophores affecting chloride ion-mediated inhibitory tonic currents. Often, a transgenic mouse model genetically lacking the δ-GABAARs (δ-KO) has been used to study the roles of δ-GABAARs in brain functions, because a specific antagonist of the δ-GABAARs is still lacking. We have previously observed with these δ-KO mice that activation of δ-GABAARs is needed for morphine-induced conditioning of place preference, and others have suggested that δ-GABAARs act as targets selectively for low doses of ethanol. Furthermore, activation of these receptors via drug-mediated agonism induces a robust increase in the slow-wave frequency bands of electroencephalography (EEG). Here, we tested δ-KO mice (compared to littermate wild-type controls) for the pharmaco-EEG responses of a broad spectrum of pharmacologically different drug classes, including alcohol, opioids, stimulants, and psychedelics. Gaboxadol (THIP), a known superagonist of δ-GABAARs, was included as the positive control, and as expected, δ-KO mice produced a blunted pharmaco-EEG response to 6 mg/kg THIP. Pharmaco-EEGs showed notable differences between treatments but also differences between δ-KO mice and their wild-type littermates. Interestingly mephedrone (4-MMC, 5 mg/kg), an amphetamine-like stimulant, had reduced effects in the δ-KO mice. The responses to ethanol (1 g/kg), LSD (0.2 mg/kg), and morphine (20 mg/kg) were similar in δ-KO and wild-type mice. Since stimulants are not known to act on δ-GABAARs, our findings on pharmaco-EEG effects of 4-MMC suggest that δ-GABAARs are involved in the secondary indirect regulation of the brain rhythms after 4-MMC.

scholarly journals The chemical induction of synaesthesia

2021 ◽  
Author(s):  
David Luke ◽  
Laura Lungu ◽  
Ross Friday ◽  
Devin Terhune
Keyword(s):  
Drug Users ◽  
Drug Class ◽  
Incidence Rates ◽  
Psychoactive Drugs ◽  
Strongly Correlated ◽  
Chemical Induction ◽  
Drug Induced ◽  
Diverse Range ◽  
Drug Classes ◽  
Multiple Drugs

Objective Preliminary research suggests that experiences resembling synaesthesia are frequently reported under the influence of a diverse range of chemical substances although the incidence, chemical specificity, and characteristics of these effects are poorly understood. Methods Here we surveyed recreational drug users and self-reported developmental synaesthetes regarding their use of 28 psychoactive drugs comprising 12 different drug classes and whether they had experienced synaesthesia under the influence of these substances. Results The drug class tryptamines exhibited the highest incidence rates of drug-induced synaesthesia in controls and induction rates of novel forms of synaesthesia in developmental synaesthetes. Induction incidence rates in controls were strongly correlated with the corresponding induction and enhancement rates in developmental synaesthetes. In addition, the use of LSD was the strongest predictor of drug-induced synaesthesia in both controls and developmental synaesthetes. Clear evidence was observed for a clustering of synaesthesia-induction rates as a function of drug class in both groups, denoting non-random incidence rates within drug classes. Sound-colour synaesthesia was the most commonly observed type of induced synaesthesia. Further analyses suggest the presence of synaesthesia-prone individuals, who were more likely to experience drug-induced synaesthesia with multiple drugs. Conclusions These data corroborate the hypothesized link between drug-induced synaesthesia and serotoninergic activity, but also suggest the possibility of alternative neurochemical pathways involved in the induction of synaesthesia. They further suggest that the induction and modulation of synaesthesia in controls and developmental synaesthetes share overlapping mechanisms and that certain individuals may be more susceptible to experiencing induced synaesthesia with different drugs.

Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain

2021 ◽  
Vol 61 (1) ◽  
pp. 181-201 ◽  
Author(s):  
Miklos Toth
Keyword(s):  
Clinical Utility ◽  
Drugs Of Abuse ◽  
Abuse Potential ◽  
Brain Functions ◽  
Epigenetic Effect ◽  
Epigenetic Effects ◽  
Drug Classes ◽  
Main Effect ◽  
And Behavior ◽  
The Brain

This review explores how different classes of drugs, including those with therapeutic and abuse potential, alter brain functions and behavior via the epigenome. Epigenetics, in its simplest interpretation, is the study of the regulation of a genes’ transcriptional potential. The epigenome is established during development but is malleable throughout life by a wide variety of drugs, with both clinical utility and abuse potential. An epigenetic effect can be central to the drug's therapeutic or abuse potential, or it can be independent from the main effect but nevertheless produce beneficial or adverse side effects. Here, I discuss the various epigenetic effects of main pharmacological drug classes, including antidepressants, antiepileptics, and drugs of abuse.

Behavioural changes induced by a conditional disruption of bone formation

2016 ◽  
Vol 27 (3) ◽  
Author(s):  
Andreas Zimmer ◽  
David-Marian Otte ◽  
Andras Bilkei-Gorzo ◽  
Samar Muhammad Armin ◽  
Itai Bab
Keyword(s):  
Bone Formation ◽  
Transgenic Mice ◽  
Bone Remodelling ◽  
Transgenic Animals ◽  
Volume Density ◽  
Wild Type ◽  
Parasympathetic Nerve ◽  
Brain Functions ◽  
Simplex Virus ◽  
The Brain

AbstractIt has been shown that the brain regulates bone remodelling through sympathetic and parasympathetic nerve fibres. However, it is unclear if signals from the skeleton also influence brain functions and animal behaviours.Bone formation was conditionally disrupted by daily injections of aciclovir (10 mg/kg) to transgenic mice expressing a herpes-simplex-virus thymidine kinase under the control of the osteoblast-specific promoter of the Bglap gene. Behavioural studies were conducted after 10 weeks of treatment.Transgenic mice receiving aciclovir injections showed a reduced number of osteoblasts with a concomitantly reduced trabecular bone volume density, when compared to wild-type controls that were treated identically. The general health of the animals was not severely affected, as indicated by a similar increase in body weight, similar activity profiles and similar social behaviours. However, transgenic mice showed significantly increased despair behaviour and increased adrenal gland weights.Specific animal behaviours can be modulated by a selective disruption of bone formation. The increased despair behaviour observed in transgenic animals indicates that these animals may be more prone to depression-related phenotypes. These findings are important in the context of the well-established clinical association between depression and reduced bone mass.

TEORI KECERDASAN, PENDIDIKAN ANAK, DAN KOMUNIKASI DALAM KELUARGA

1970 ◽  
Vol 6 (1) ◽  
Author(s):  
Muskinul Fuad
Keyword(s):  
Multiple Intelligences ◽  
Educational Activity ◽  
Howard Gardner ◽  
Human Beings ◽  
Brain Functions ◽  
Starting Point ◽  
The Family ◽  
Education Today ◽  
The Brain ◽  
Spatial Logics

The education system in Indonesia emphasize on academic intelligence, whichincludes only two or three aspects, more than on the other aspects of intelligence. For thatreason, many children who are not good at academic intelligence, but have good potentials inother aspects of intelligence, do not develop optimally. They are often considered and labeledas "stupid children" by the existing system. This phenomenon is on the contrary to the theoryof multiple intelligences proposed by Howard Gardner, who argues that intelligence is theability to solve various problems in life and produce products or services that are useful invarious aspects of life.Human intelligence is a combination of various general and specific abilities. Thistheory is different from the concept of IQ (intelligence quotient) that involves only languageskills, mathematical, and spatial logics. According to Gardner, there are nine aspects ofintelligence and its potential indicators to be developed by each child born without a braindefect. What Gardner suggested can be considered as a starting point to a perspective thatevery child has a unique individual intelligence. Parents have to treat and educate theirchildren proportionally and equitably. This treatment will lead to a pattern of education that isfriendly to the brain and to the plurality of children’s potential.More than the above points, the notion that multiple intelligences do not just comefrom the brain needs to be followed. Humans actually have different immaterial (spiritual)aspects that do not refer to brain functions. The belief in spiritual aspects and its potentialsmeans that human beings have various capacities and they differ from physical capacities.This is what needs to be addressed from the perspective of education today. The philosophyand perspective on education of the educators, education stakeholders, and especially parents,are the first major issue to be addressed. With this step, every educational activity andcommunication within the family is expected to develop every aspect of children'sintelligence, especially the spiritual intelligence.

CCR5 deficiency decreases susceptibility to experimental cerebral malaria

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4253-4259 ◽  
Author(s):  
Elodie Belnoue ◽  
Michèle Kayibanda ◽  
Jean-Christophe Deschemin ◽  
Mireille Viguier ◽  
Matthias Mack ◽  
...  
Keyword(s):  
T Cells ◽  
Cerebral Malaria ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Wild Type ◽  
Experimental Cerebral Malaria ◽  
Pathologic Features ◽  
Th1 Cytokine ◽  
The Brain ◽  
Deficient Mice

Abstract Infection of susceptible mouse strains with Plasmodium berghei ANKA (PbA) is a valuable experimental model of cerebral malaria (CM). Two major pathologic features of CM are the intravascular sequestration of infected erythrocytes and leukocytes inside brain microvessels. We have recently shown that only the CD8+ T-cell subset of these brain-sequestered leukocytes is critical for progression to CM. Chemokine receptor–5 (CCR5) is an important regulator of leukocyte trafficking in the brain in response to fungal and viral infection. Therefore, we investigated whether CCR5 plays a role in the pathogenesis of experimental CM. Approximately 70% to 85% of wild-type and CCR5+/- mice infected with PbA developed CM, whereas only about 20% of PbA-infected CCR5-deficient mice exhibited the characteristic neurologic signs of CM. The brains of wild-type mice with CM showed significant increases in CCR5+ leukocytes, particularly CCR5+ CD8+ T cells, as well as increases in T-helper 1 (Th1) cytokine production. The few PbA-infected CCR5-deficient mice that developed CM exhibited a similar increase in CD8+ T cells. Significant leukocyte accumulation in the brain and Th1 cytokine production did not occur in PbA-infected CCR5-deficient mice that did not develop CM. Moreover, experiments using bone marrow (BM)–chimeric mice showed that a reduced but significant proportion of deficient mice grafted with CCR5+ BM develop CM, indicating that CCR5 expression on a radiation-resistant brain cell population is necessary for CM to occur. Taken together, these results suggest that CCR5 is an important factor in the development of experimental CM.

scholarly journals (Ascorb)ing Pb Neurotoxicity in the Developing Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1311
Author(s):  
Faraz Ahmad ◽  
Ping Liu
Keyword(s):  
Ascorbic Acid ◽  
Animal Studies ◽  
Redox Homeostasis ◽  
Special Role ◽  
Developmental Exposure ◽  
Brain Functions ◽  
Brain States ◽  
Pb Exposure ◽  
The Brain ◽  
Potent Therapeutic Agent

Lead (Pb) neurotoxicity is a major concern, particularly in children. Developmental exposure to Pb can alter neurodevelopmental trajectory and has permanent neuropathological consequences, including an increased vulnerability to further stressors. Ascorbic acid is among most researched antioxidant nutrients and has a special role in maintaining redox homeostasis in physiological and physio-pathological brain states. Furthermore, because of its capacity to chelate metal ions, ascorbic acid may particularly serve as a potent therapeutic agent in Pb poisoning. The present review first discusses the major consequences of Pb exposure in children and then proceeds to present evidence from human and animal studies for ascorbic acid as an efficient ameliorative supplemental nutrient in Pb poisoning, with a particular focus on developmental Pb neurotoxicity. In doing so, it is hoped that there is a revitalization for further research on understanding the brain functions of this essential, safe, and readily available vitamin in physiological states, as well to justify and establish it as an effective neuroprotective and modulatory factor in the pathologies of the nervous system, including developmental neuropathologies.

Simulation of sports movement training based on machine learning and brain-computer interface

2020 ◽  
pp. 1-12
Author(s):  
Linuo Wang
Keyword(s):  
Machine Learning ◽  
Time Series ◽  
Joint Learning ◽  
Scientific Methods ◽  
Learning Framework ◽  
Brain Functions ◽  
Movement Training ◽  
Practical Effect ◽  
Machine Interface ◽  
The Brain

Injuries and hidden dangers in training have a greater impact on athletes ’careers. In particular, the brain function that controls the motor function area has a greater impact on the athlete ’s competitive ability. Based on this, it is necessary to adopt scientific methods to recognize brain functions. In this paper, we study the structure of motor brain-computer and improve it based on traditional methods. Moreover, supported by machine learning and SVM technology, this study uses a DSP filter to convert the preprocessed EEG signal X into a time series, and adjusts the distance between the time series to classify the data. In order to solve the inconsistency of DSP algorithms, a multi-layer joint learning framework based on logistic regression model is proposed, and a brain-machine interface system of sports based on machine learning and SVM is constructed. In addition, this study designed a control experiment to improve the performance of the method proposed by this study. The research results show that the method in this paper has a certain practical effect and can be applied to sports.

scholarly journals Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Katherine M Ranard ◽  
Matthew J Kuchan ◽  
John W Erdman
Keyword(s):  
Animal Model ◽  
Vitamin E ◽  
Mouse Model ◽  
Wild Type ◽  
Future Studies ◽  
Neurological Outcomes ◽  
Transfer Protein ◽  
And Function ◽  
The Brain ◽  
Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

scholarly journals Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons

2020 ◽  
Vol 22 (1) ◽  
pp. 145
Author(s):  
Rohan Umesh Parekh ◽  
Srinivas Sriramula
Keyword(s):  
Protein Expression ◽  
Renin Angiotensin System ◽  
Neuronal Cultures ◽  
Wild Type ◽  
High Concentration ◽  
Neurogenic Hypertension ◽  
B1 Receptor ◽  
Gene And Protein Expression ◽  
Kinin B1 Receptor ◽  
Specific Antagonist

Angiotensin converting enzyme 2 (ACE2) is a critical component of the compensatory axis of the renin angiotensin system. Alterations in ACE2 gene and protein expression, and activity mediated by A Disintegrin And Metalloprotease 17 (ADAM17), a member of the “A Disintegrin And Metalloprotease” (ADAM) family are implicated in several cardiovascular and neurodegenerative diseases. We previously reported that activation of kinin B1 receptor (B1R) in the brain increases neuroinflammation, oxidative stress and sympathoexcitation, leading to the development of neurogenic hypertension. We also showed evidence for ADAM17-mediated ACE2 shedding in neurons. However, whether kinin B1 receptor (B1R) activation has any role in altering ADAM17 activity and its effect on ACE2 shedding in neurons is not known. In this study, we tested the hypothesis that activation of B1R upregulates ADAM17 and results in ACE2 shedding in neurons. To test this hypothesis, we stimulated wild-type and B1R gene-deleted mouse neonatal primary hypothalamic neuronal cultures with a B1R-specific agonist and measured the activities of ADAM17 and ACE2 in neurons. B1R stimulation significantly increased ADAM17 activity and decreased ACE2 activity in wild-type neurons, while pretreatment with a B1R-specific antagonist, R715, reversed these changes. Stimulation with specific B1R agonist Lys-Des-Arg9-Bradykinin (LDABK) did not show any effect on ADAM17 or ACE2 activities in neurons with B1R gene deletion. These data suggest that B1R activation results in ADAM17-mediated ACE2 shedding in primary hypothalamic neurons. In addition, stimulation with high concentration of glutamate significantly increased B1R gene and protein expression, along with increased ADAM17 and decreased ACE2 activities in wild-type neurons. Pretreatment with B1R-specific antagonist R715 reversed these glutamate-induced effects suggesting that indeed B1R is involved in glutamate-mediated upregulation of ADAM17 activity and ACE2 shedding.

scholarly journals BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud Harb ◽  
Justina Jagusch ◽  
Archana Durairaja ◽  
Thomas Endres ◽  
Volkmar Leßmann ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Sensorimotor Gating ◽  
Enriched Environment ◽  
Fear Learning ◽  
Set Shifting ◽  
Wild Type ◽  
Mature Adult ◽  
Attentional Set ◽  
Attentional Set Shifting ◽  
The Brain

AbstractBrain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF’s role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF+/−) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/− mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/− mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/− mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.

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