scholarly journals Peri-adolescent THC exposure does not lead to anxiety-like behavior in adult mice

2020 ◽  
Author(s):  
Matija Sestan-Pesa ◽  
Marya Shanabrough ◽  
Tamas L. Horvath ◽  
Maria Consolata Miletta
Keyword(s):  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Wild Type ◽  
Growth Hormone Secretagogue Receptor ◽  
Male Adult ◽  
Growth Hormone Secretagogue ◽  
Adult Mice ◽  
Marijuana Consumption ◽  
Long Term Impact

AbstractAs marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illness, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the gut and is important for feeding behavior. Recent studies have shown that ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) play important roles in mediating stress, as well as anxiety and, depression-like behaviors in animal models. Here, we investigated the effects of chronic Tetrahydrocannabinol (THC) administration during adolescence (P42-55), in GHSR (GHSR-/-) knockout mice and their wild type littermates in relation to anxiety-like behaviors. We found that continuous THC exposure during peri-adolescence did not lead to any significant alterations in anxiety-like behavior of male adult mice, regardless of genotype. These data indicate that in the presence of intact GHSR signaling, THC exposure during peri-adolescence has limited if any long term impact on anxiety-like behaviors in mice.

scholarly journals Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Plank ◽  
Stefan Frey ◽  
Lukas Andreas Basedow ◽  
Jalal Solati ◽  
Fabio Canneva ◽  
...  
Keyword(s):  
Stress Reactivity ◽  
Dorsal Hippocampus ◽  
Methylation Status ◽  
Stress Axis ◽  
Mrna Levels ◽  
Fk506 Binding Protein ◽  
Adult Mice ◽  
Stress Related Genes ◽  
Long Term Impact

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

scholarly journals The Developmental Role of Serotonin: A Comparison of Short- and Long-term Blockade of the Serotonin Transporter on Behavioural Outcomes in Adulthood

2021 ◽  
Author(s):  
◽  
Amy O'Connell
Keyword(s):  
Animal Model ◽  
Serotonin Transporter ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Critical Periods ◽  
Significant Group ◽  
Fluoxetine Treatment ◽  
Short And Long Term

<p>Serotonin is an important neurotransmitter that regulates a range of processes within the brain and is implicated in several psychiatric disorders. In addition, serotonin acts as a developmental signal during critical periods of prenatal development, influencing processes such as neuronal proliferation, migration, and synaptogenesis (Gaspar et al., 2003). The serotonin transporter (5- HTT) plays a key role in regulating extracellular serotonin levels and is the main target of selective-serotonin reuptake inhibitors (SSRIs), a class of drugs that have anti-anxiety and anti- depressive activity. SSRIs cause an acute increase in extracellular serotonin and are commonly prescribed as a treatment for depression and anxiety during pregnancy (Tran & Robb, 2015). Given that these drugs alter serotonin transmission and can pass to the developing fetus via the placenta, it is vital that the outcomes of prenatal SSRI exposure are investigated. In humans, a genetic variant of the gene that codes for the 5-HTT (SLC6A4) has been linked to increased risk for developing depression and anxiety (Caspi et al., 2003). The functional consequences of this genetic polymorphism are life-long alterations in 5-HTT activity, resulting in increased extracellular levels of serotonin (Nakamura et al., 2000). Given prenatal SSRI exposure results in a time-locked blockade of 5-HTT during critical periods of development, it follows that alterations in serotonin during development might similarly result in enhanced risk for depression and anxiety later in life. Outcomes in children prenatally exposed to SSRIs are difficult to study due to confounds of pre- existing maternal depression. Therefore, the current thesis presents two experiments that aimed to further investigate the role of altered extracellular serotonin levels during development in an animal model. Experiment one aimed to develop a method of voluntary oral administration of the SSRI fluoxetine to pregnant rat dams. This method was then applied in experiment two to create a time-locked blockade of 5-HTT during critical periods of development in an animal model of life-long 5-HTT blockade. The aim of experiment two was to directly assess the contribution of short- and long-term 5-HTT blockade on anxiety and depression phenotypes in adult male offspring. In addition, maternal behaviour was assessed to determine whether fluoxetine treatment had an influence on mother-pup interactions that could confound results. To test for anxiety and depression phenotypes, the novel affective disorder test (ADT) was used to assess anxiety behaviour and the deficits in anticipatory pleasure indicative of anhedonia. In the current study, fluoxetine treatment did not have an effect on litter outcomes or mother-pup interactions. Crucially, no significant group differences were found indicating that neither short- nor long- term blockade of 5-HTT resulted in increased anxiety- or depressive-like behaviours in the current experiment. However, limitations with methodological design limit the translatability of these results to the broader literature, and validation of the ADT is required before these results can be generalised beyond this thesis.</p>

scholarly journals MENTAL ILL-HEALTH AND HEART FAILURE COMORBIDITY

2019 ◽  
pp. 11-17
Author(s):  
MARIAM AHMED ◽  
HANA MORRISSEY ◽  
PATRICK ANTHONY BALL
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Health Outcomes ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Disease Modification ◽  
Patient Health ◽  
The Cost ◽  
Adherence To Therapy

This review aims to understand the co-existence of mental ill-health and heart failure and if this comorbidity affects patient self-care motivation and overall health outcomes. Databases searched were; PubMed®, Google® scholar and Science Direct® for studies related to heart failure, heart failure and mental health, depression and anxiety. Eleven articles were identified and reviewed. There were two studies disagreed with the theory that the mental ill-health and heart failure has disease modification and worsen patient health outcomes, three studies concluded that only anxiety has effect, five studies concluded that both anxiety and depression have effect, six studies concluded that depression only has effect but all eleven stated that more research is required. Recent theories on depression and cardiovascular disease comorbidity and the effect mental ill-health have on medication adherence in heart failure patients was discussed. People with long-term physical illnesses may suffer further complications to their health if they develop mental illness; increasing the cost of their care by an average of 45%, however, in the majority of these cases, the mental issues neither diagnosed nor treated. This review explored the link between cardiovascular disease (CVD) and mental ill health; and how comorbidity of the two conditions affects patients’ adherence to therapy behaviour. It was concluded that while the link between mental ill health and heart failure (HF) is recognized, studies that may be used as a basis of evidence to confirm this link are scarce.

scholarly journals QOLP-17. FACTORS ASSOCIATED WITH PSYCHOLOGICAL DISTRESS IN CAREGIVERS OF PATIENTS WITH MALIGNANT GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi201-vi201
Author(s):  
Sophia Landay ◽  
Maya Anand ◽  
Nora Horick ◽  
Jamie Jacobs ◽  
Kit Quain ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Malignant Gliomas ◽  
Tumor Location ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Wild Type ◽  
Related Factors ◽  
Caregiver Depression ◽  
Factors Associated ◽  
Caregiver Anxiety

Abstract BACKGROUND Caregivers of patients with newly diagnosed malignant gliomas experience high rates of psychological distress. However, the factors associated with distress in this population have not been well described. We sought to evaluate patient-related, caregiver-related and tumor-related factors associated with depression and anxiety in this caregiver population. METHODS We conducted a prospective study in patients with newly diagnosed malignant gliomas and their caregivers, collecting self-report data within 6 weeks of diagnosis. Patients’ and caregivers’ depression and anxiety were assessed using the Hospital Anxiety and Depression Scale, with subscale scores >7 considered clinically significant. Information about the tumor location and molecular features was extracted from the medical record. We used univariate and multivariate linear models to evaluate the association between caregiver anxiety and depression at baseline and specific caregiver-, patient- and tumor-related factors. RESULTS We enrolled 61 patient-caregiver dyads in this study. 26.2% (16/61) of caregivers had significant depression symptoms, and 47.5% (29/61) had significant anxiety. In the multivariable analysis, factors associated with higher caregiver depression score included younger caregiver age (< 65 years old; B=4.24, p=0.0002), left-sided tumor location (B=1.98, p=0.030), IDH wild-type tumor status (B=3.44, p=0.0008) and patient anxiety (B=2.28, p=0.017). Factors associated with higher caregiver anxiety were younger caregiver age (B=2.47, p=0.089) and left-sided tumor location (B=4.23, p=0.001). CONCLUSIONS Younger caregiver age and caring for a patient with a tumor on the left side of the brain were associated with worse caregiver depression and anxiety. Higher caregiver depression was correlated with caregivers whose loved one had significant anxiety or had an IDH wild-type tumor. Understanding the factors associated with caregiver anxiety and depression may guide neuro-oncology clinicians in identifying caregivers who may be at an increased risk for psychological distress at the time of their loved one’s diagnosis, allowing for earlier initiation of support services for these caregivers.

SOME ASPECTS OF ZONATION AND FUNCTION OF THE ADRENAL CORTEX

1954 ◽  
Vol 10 (3) ◽  
pp. 245-NP ◽  
Author(s):  
I. CHESTER JONES ◽  
C. C. ROBY
Keyword(s):  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Male Adult ◽  
Sodium Potassium ◽  
Potassium Intake ◽  
Adult Mice ◽  
Water Output ◽  
And Function ◽  
Sodium And Potassium

SUMMARY Male adult mice, 80 days after hypophysectomy, show approximately the same pattern of sodium and potassium intake and sodium, potassium and water output as normal mice. The healthy remnant of adrenal cortex left after the operation is thought to be responsible for the day-to-day competence of the hypophysectomized animal in salt-electrolyte metabolism. The histology of the cortex is described and it is shown that, with the injection of ACTH, a cortex of normal appearance can be regenerated from the persistent zona glomerulosa of the long-term hypophysectomized mouse.

scholarly journals Anxiety and Depression in Patients Hospitalized With Chronic Kidney Disease in Barranquilla Clinics, Colombia

2018 ◽  
Vol 10 (11) ◽  
pp. 144
Author(s):  
Carmen A. Sierra Llamas ◽  
Rafael E. Donado Castillo ◽  
Gustavo Aroca ◽  
Santos Ángel Depine ◽  
Gladys Gaviria ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Population Group ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Short Term ◽  
The Individual ◽  
New Research ◽  
The City

The purpose of this study is to determine the levels of anxiety and depression in patients aged between 18 and 70 years, hospitalized with chronic kidney disease in a clinic entity of the city of Barranquilla. The type of research is descriptive, presenting the information through the indicators and statistical tables, the Hospital Scale of Anxiety and Depression of, Zigmond &amp; Smith (1983), which evaluates the detection of depressive and anxious disorders in the non-psychiatric hospital context. The application of the Scale was performed in the hospital entity of the city of Barranquilla to 50 patients with Chronic Kidney Disease. The results they are beneficial in the short term, because they create new research proposals applied to another population group diagnosed with chronic diseases, especially for the evaluation and intervention in the area of health psychology. In the long term, new theories, methods of intervention and evaluation applied to the population of patients with chronic kidney disease will be studied. In the same way, the results show marked trends related to depression, an aspect that is consistent with the deterioration that affects the individual in the course of the disease and also show a positive correlation of the study variables, depression and anxiety disorders in patients with CKD can be due to a symptomatology or consequence of psychological burnout.

scholarly journals Selectively increasing GHS-R1a expression in dCA1 excitatory/inhibitory neurons have opposite effects on memory encoding

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nan Li ◽  
Na Li ◽  
Fenghua Xu ◽  
Ming Yu ◽  
Zichen Qiao ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Memory Performance ◽  
Critical Role ◽  
Inhibitory Neurons ◽  
Long Term Memory ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Term Memory ◽  
Selective Increase

Abstract Aim Growth hormone secretagogue receptor 1a (GHS-R1a) is widely distributed in brain including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology, memory and cognitive dysfunction associated with Alzheimer’s disease (AD). However, current reports are inconsistent, and the mechanism underlying memory modulation of GHS-R1a signaling is uncertain. In this study, we aim to investigate the direct impact of selective increase of GHS-R1a expression in dCA1 excitatory/inhibitory neurons on learning and memory. Methods Endogenous GHS-R1a distribution in dCA1 excitatory/inhibitory neurons was assessed by fluorescence in situ hybridization. Cre-dependent GHS-R1a overexpression in excitatory or inhibitory neurons was done by stereotaxic injection of aav-hSyn-DIO-hGhsr1a-2A-eGFP virus in dCA1 region of vGlut1-Cre or Dlx5/6-Cre mice respectively. Virus-mediated GHS-R1a upregulation in dCA1 neurons was confirmed by quantitative RT-PCR. Different behavioral paradigms were used to evaluate long-term memory performance. Results GHS-R1a is distributed both in dCA1 excitatory pyramidal neurons (αCaMKII+) and in inhibitory interneurons (GAD67+). Selective increase of GHS-R1a expression in dCA1 pyramidal neurons impaired spatial memory and object-place recognition memory. In contrast, selective increase of GHS-R1a expression in dCA1 interneurons enhanced long-term memory performance. Our findings reveal, for the first time, a neuronal type-specific role that hippocampal GHS-R1a signaling plays in regulating memory. Therefore, manipulating GHS-R1a expression/activity in different subpopulation of neurons may help to clarify current contradictory findings and to elucidate mechanism of memory control by ghrelin/GHS-R1a signaling, under both physiological and pathological conditions such as AD.

scholarly journals The Developmental Role of Serotonin: A Comparison of Short- and Long-term Blockade of the Serotonin Transporter on Behavioural Outcomes in Adulthood

2021 ◽  
Author(s):  
◽  
Amy O'Connell
Keyword(s):  
Animal Model ◽  
Serotonin Transporter ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Critical Periods ◽  
Significant Group ◽  
Fluoxetine Treatment ◽  
Short And Long Term

<p>Serotonin is an important neurotransmitter that regulates a range of processes within the brain and is implicated in several psychiatric disorders. In addition, serotonin acts as a developmental signal during critical periods of prenatal development, influencing processes such as neuronal proliferation, migration, and synaptogenesis (Gaspar et al., 2003). The serotonin transporter (5- HTT) plays a key role in regulating extracellular serotonin levels and is the main target of selective-serotonin reuptake inhibitors (SSRIs), a class of drugs that have anti-anxiety and anti- depressive activity. SSRIs cause an acute increase in extracellular serotonin and are commonly prescribed as a treatment for depression and anxiety during pregnancy (Tran & Robb, 2015). Given that these drugs alter serotonin transmission and can pass to the developing fetus via the placenta, it is vital that the outcomes of prenatal SSRI exposure are investigated. In humans, a genetic variant of the gene that codes for the 5-HTT (SLC6A4) has been linked to increased risk for developing depression and anxiety (Caspi et al., 2003). The functional consequences of this genetic polymorphism are life-long alterations in 5-HTT activity, resulting in increased extracellular levels of serotonin (Nakamura et al., 2000). Given prenatal SSRI exposure results in a time-locked blockade of 5-HTT during critical periods of development, it follows that alterations in serotonin during development might similarly result in enhanced risk for depression and anxiety later in life. Outcomes in children prenatally exposed to SSRIs are difficult to study due to confounds of pre- existing maternal depression. Therefore, the current thesis presents two experiments that aimed to further investigate the role of altered extracellular serotonin levels during development in an animal model. Experiment one aimed to develop a method of voluntary oral administration of the SSRI fluoxetine to pregnant rat dams. This method was then applied in experiment two to create a time-locked blockade of 5-HTT during critical periods of development in an animal model of life-long 5-HTT blockade. The aim of experiment two was to directly assess the contribution of short- and long-term 5-HTT blockade on anxiety and depression phenotypes in adult male offspring. In addition, maternal behaviour was assessed to determine whether fluoxetine treatment had an influence on mother-pup interactions that could confound results. To test for anxiety and depression phenotypes, the novel affective disorder test (ADT) was used to assess anxiety behaviour and the deficits in anticipatory pleasure indicative of anhedonia. In the current study, fluoxetine treatment did not have an effect on litter outcomes or mother-pup interactions. Crucially, no significant group differences were found indicating that neither short- nor long- term blockade of 5-HTT resulted in increased anxiety- or depressive-like behaviours in the current experiment. However, limitations with methodological design limit the translatability of these results to the broader literature, and validation of the ADT is required before these results can be generalised beyond this thesis.</p>

Forebrain Acetylcholine Modulates Isoflurane and Ketamine Anesthesia in Adult Mice

2021 ◽  
Vol 134 (4) ◽  
pp. 588-606 ◽  
Author(s):  
L. Stan Leung ◽  
Liangwei Chu ◽  
Marco A. M. Prado ◽  
Vania F. Prado
Keyword(s):  
Interaction Effect ◽  
Gamma Activity ◽  
Wild Type ◽  
Male Adult ◽  
Adult Mice ◽  
Loss Of Righting Reflex ◽  
High Gamma ◽  
Ketamine Anesthesia ◽  
Gamma Power ◽  
Righting Reflex

Background Cholinergic drugs are known to modulate general anesthesia, but anesthesia responses in acetylcholine-deficient mice have not been studied. It was hypothesized that mice with genetic deficiency of forebrain acetylcholine show increased anesthetic sensitivity to isoflurane and ketamine and decreased gamma-frequency brain activity. Methods Male adult mice with heterozygous knockdown of vesicular acetylcholine transporter in the brain or homozygous knockout of the transporter in the basal forebrain were compared with wild-type mice. Hippocampal and frontal cortical electrographic activity and righting reflex were studied in response to isoflurane and ketamine doses. Results The loss-of-righting-reflex dose for isoflurane was lower in knockout (mean ± SD, 0.76 ± 0.08%, n = 18, P = 0.005) but not knockdown (0.78 ± 0.07%, n = 24, P = 0.021), as compared to wild-type mice (0.83 ± 0.07%, n = 23), using a significance criterion of P = 0.017 for three planned comparisons. Loss-of-righting-reflex dose for ketamine was lower in knockout (144 ± 39 mg/kg, n = 14, P = 0.006) but not knockdown (162 ± 32 mg/kg, n = 20, P = 0.602) as compared to wild-type mice (168 ± 24 mg/kg, n = 21). Hippocampal high-gamma (63 to 100 Hz) power after isoflurane was significantly lower in knockout and knockdown mice compared to wild-type mice (isoflurane-dose and mouse-group interaction effect, F[8,56] = 2.87, P = 0.010; n = 5 to 6 mice per group). Hippocampal high-gamma power after ketamine was significantly lower in both knockout and knockdown mice when compared to wild-type mice (interaction effect F[2,13] = 6.06, P = 0.014). The change in frontal cortical gamma power with isoflurane or ketamine was not statistically different among knockout, knockdown, and wild-type mice. Conclusions These findings suggest that forebrain cholinergic neurons modulate behavioral sensitivity and hippocampal gamma activity during isoflurane and ketamine anesthesia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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