scholarly journals Sex-dependent changes in murine striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence

2021 ◽  
Author(s):  
Andrew J. Kesner ◽  
Yolanda Mateo ◽  
Karina P. Abrahao ◽  
Stephanie Ramos-Maciel ◽  
Matthew J. Pava ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Animal Studies ◽  
Brain Slices ◽  
Withdrawal Symptoms ◽  
Exposure Model ◽  
Sleep Disruption ◽  
Clinical Observations ◽  
Induced Changes ◽  
And Behavior ◽  
Da Release

AbstractWithdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance inducing THC treatment. Sex differences were observed in nearly all metrics. Altered striatal DA release, sleep and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. To our knowledge these findings provide the first model of directly translatable non-precipitated cannabis withdrawal symptoms, in particular, sleep disruption.

scholarly journals Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

2021 ◽  
pp. 074873042098732
Author(s):  
N. Kronfeld-Schor ◽  
T. J. Stevenson ◽  
S. Nickbakhsh ◽  
E. S. Schernhammer ◽  
X. C. Dopico ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Multidisciplinary Approach ◽  
Preliminary Assessment ◽  
Epidemiological Evidence ◽  
Wide Range ◽  
Human Coronaviruses ◽  
Induced Changes ◽  
And Behavior ◽  
Timing Phase

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

Maternal immune and affiliative biomarkers and sensitive parenting mediate the effects of chronic early trauma on child anxiety

2017 ◽  
Vol 48 (6) ◽  
pp. 1020-1033 ◽  
Author(s):  
A. Ulmer-Yaniv ◽  
A. Djalovski ◽  
K. Yirmiya ◽  
G. Halevi ◽  
O. Zagoory-Sharon ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Chronic Stress ◽  
Animal Studies ◽  
Stress Reactivity ◽  
Child Anxiety ◽  
Anxiety Symptoms ◽  
Analysis Model ◽  
Post Traumatic Stress ◽  
And Behavior ◽  
Early Trauma

BackgroundChronic early trauma alters children's stress reactivity and increases the prevalence of anxiety disorders; yet the neuroendocrine and immune mechanisms underpinning this effect are not fully clear. Animal studies indicate that the mother's physiology and behavior mediate offspring stress in a system-specific manner, but few studies tested this external-regulatory maternal role in human children exposed to chronic stress.MethodsWe followed a unique cohort of children exposed to continuous wartime trauma (N= 177; exposed;N= 101, controls;N= 76). At 10 years, maternal and child's salivary immunoglobulin A (s-IgA) and oxytocin (OT), biomarkers of the immune and affiliation systems, were assayed, maternal and child relational behaviors observed, mother and child underwent psychiatric diagnosis, and child anxiety symptoms assessed.ResultsWar-exposed mothers had higher s-IgA, lower OT, more anxiety symptoms, and their parenting was characterized by reduced sensitivity. Exposed children showed higher s-IgA, more anxiety disorders and post traumatic stress disorder, and more anxiety symptoms. Path analysis model defined three pathways by which maternal physiology and behavior impacted child anxiety; (a) increasing maternal s-IgA, which led to increased child s-IgA, augmenting child anxiety; (b) reducing maternal OT, which linked with diminished child OT and social repertoire; and (c) increasing maternal anxiety, which directly impacted child anxiety.ConclusionsOur findings, the first to measure immune and affiliation biomarkers in mothers and children, detail their unique and joint effects on children's anxiety in response to stress; highlight the relations between chronic stress, immune activation, and anxiety in children; and describe how processes of biobehavioral synchrony shape children's long-term adaptation.

scholarly journals Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity

2021 ◽  
Vol 17 (3) ◽  
pp. e1009324
Author(s):  
Lucas dos Santos Dias ◽  
Hannah E. Dobson ◽  
Brock Kingstad Bakke ◽  
Gregory C. Kujoth ◽  
Junfeng Huang ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Influenza A ◽  
Fungal Pathogens ◽  
Animal Studies ◽  
Structural Basis ◽  
Viral Immunity ◽  
Mucosal Vaccination ◽  
Clinical Observations ◽  
Protective Antibodies ◽  
Anti Fungal

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.

scholarly journals AMPed-up adolescents: the role of age in the abuse of amphetamines and its consequences on cognition and prefrontal cortex development

2020 ◽  
Author(s):  
Sara Ruth Westbrook ◽  
Lauren Carrica ◽  
Asia Banks ◽  
Joshua Michael Gulley
Keyword(s):  
Prefrontal Cortex ◽  
Animal Studies ◽  
Drug Effects ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Vulnerability Factors ◽  
Brain And Behavior ◽  
And Behavior ◽  
Detrimental Impact

Adolescent use of amphetamine and its closely related, methylated version methamphetamine, is alarmingly high in those who use drugs for nonmedical purposes. This raises serious concerns about the potential for this drug use to have a long-lasting, detrimental impact on the normal development of the brain and behavior that is ongoing during adolescence. In this review, we explore recent findings from both human and laboratory animal studies that investigate the consequences of amphetamine and methamphetamine exposure during this stage of life. We highlight studies that assess sex differences in adolescence, as well as those that are designed specifically to address the potential unique effects of adolescent exposure by including groups at other life stages (typically young adulthood). We consider epidemiological studies on age and sex as vulnerability factors for developing problems with the use of amphetamines, as well as human and animal laboratory studies that tap into age differences in use, its short-term effects on behavior, and the long-lasting consequences of this exposure on cognition. We also focus on studies of drug effects in the prefrontal cortex, which is known to be critically important for cognition and is among the later maturing brain regions. Finally, we discuss important issues that should be addressed in future studies so that the field can further our understanding of the mechanisms underlying adolescent use of amphetamines and its outcomes on the developing brain and behavior.

scholarly journals Acute oral toxicity study of GAL-57 (Bentazon + Dicamba) herbicide in rats

2009 ◽  
Vol 24 (3) ◽  
pp. 221-226 ◽  
Author(s):  
Dragica Brkic ◽  
Slavica Gasic ◽  
Nesko Neskovic
Keyword(s):  
Clinical Symptoms ◽  
Toxicity Study ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Time Intervals ◽  
Group Iii ◽  
Clinical Observations ◽  
Righting Reflex ◽  
And Behavior ◽  
Observation Period

An acute oral toxicity study of the herbicide GAL-57 (Avalon), a mixture of bentazon and dicamba as active ingredients, was investigated on rats, using a new method that has been used in the past several years (2001). Clinical observations symptoms and mortality were performed for all animals in different time intervals after treatment, and gross necropsy was performed at the end of observation period. Clinical symptoms (decreased activity, prone position, abnormal limb position, decreased righting reflex, decreased grip and limb tone, decreased body and abdominal tone, dyspnoea) of marked degree were noted after administration of 2000 mg/kg, and animals were dead in the period of 30-60 minutes after the treatment. GAL-57 did not cause any clinical sings at single 300 mg/kg bw dose. The physical condition and behavior of animals (males and females) were normal, and it is not differ in reaction to the control. According to the methodology used in the present study, it could be concluded that the acute oral LD-50 value of the GAL-57 proved to be between 300 and 2000 mg/kg body weight in rats, and the product was ranked into Poison group III according to Serbian criteria, category 4 of the Global Harmonized Classification System, and Category III of the EPA classification.

Speculations on Antineuronal Antibody-Mediated Neuropsychiatric Disorders of Childhood

PEDIATRICS ◽  
1994 ◽  
Vol 93 (2) ◽  
pp. 323-326 ◽  
Author(s):  
Susan E. Swedo ◽  
Henrietta L. Leonard ◽  
Louise S. Kiessling
Keyword(s):  
Sleep Disturbances ◽  
Obsessive Compulsive ◽  
Behavioral Disturbances ◽  
Obsessive Compulsive Symptoms ◽  
Antineuronal Antibodies ◽  
Compulsive Disorder ◽  
Clinical Observations ◽  
Neurological Abnormalities ◽  
Group A ◽  
The Central Nervous System

Several converging lines of evidence suggest that some behavioral and neurological abnormalities of childhood may be mediated through antineuronal antibodies.1-3 These antineuronal antibodies appear to arise in response to group A [beta]-hemolytic streptococcal (GABHS) infections and to cross-react with cells within the central nervous system (CNS).4 Based on clinical observations of children with Sydenham's chorea, Tourette's syndrome (TS), and/or obsessive-compulsive disorder (OCD), we hypothesize that neuroimmunological dysfunction secondary to anti-neuronal antibodies may result in behavioral disturbances, such as anxiety, emotional lability, obsessive compulsive symptoms, hyperactivity, and sleep disturbances; and neurological abnormalities, such as motor and phonic tics, ballismus, chorea, and choreiform movements.

scholarly journals Developmental Regulation of Basket Interneuron Synapses and Behavior through NCAM in Mouse Prefrontal Cortex

2020 ◽  
Vol 30 (8) ◽  
pp. 4689-4707
Author(s):  
Chelsea S Sullivan ◽  
Vishwa Mohan ◽  
Paul B Manis ◽  
Sheryl S Moy ◽  
Young Truong ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Developmental Regulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Electrophysiological Recording ◽  
Network Function ◽  
Growth Cone Collapse ◽  
Layer 2 ◽  
And Behavior

Abstract Parvalbumin (PV)-expressing basket interneurons in the prefrontal cortex (PFC) regulate pyramidal cell firing, synchrony, and network oscillations. Yet, it is unclear how their perisomatic inputs to pyramidal neurons are integrated into neural circuitry and adjusted postnatally. Neural cell adhesion molecule NCAM is expressed in a variety of cells in the PFC and cooperates with EphrinA/EphAs to regulate inhibitory synapse density. Here, analysis of a novel parvalbumin (PV)-Cre: NCAM F/F mouse mutant revealed that NCAM functions presynaptically in PV+ basket interneurons to regulate postnatal elimination of perisomatic synapses. Mutant mice exhibited an increased density of PV+ perisomatic puncta in PFC layer 2/3, while live imaging in mutant brain slices revealed fewer puncta that were dynamically eliminated. Furthermore, EphrinA5-induced growth cone collapse in PV+ interneurons in culture depended on NCAM expression. Electrophysiological recording from layer 2/3 pyramidal cells in mutant PFC slices showed a slower rise time of inhibitory synaptic currents. PV-Cre: NCAM F/F mice exhibited impairments in working memory and social behavior that may be impacted by altered PFC circuitry. These findings suggest that the density of perisomatic synapses of PV+ basket interneurons is regulated postnatally by NCAM, likely through EphrinA-dependent elimination, which is important for appropriate PFC network function and behavior.

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