Identification of a novel fatty acid binding protein-5-CB2 receptor-dependent mechanism regulating anxiety behaviors in the prefrontal cortex.

The endocannabinoid (eCB) system represents a promising neurobiological target for novel anxiolytic pharmacotherapies. Previous clinical and preclinical evidence has revealed that genetic and/or pharmacological manipulations altering eCB signaling modulate fear and anxiety behaviors. Water-insoluble eCB lipid anandamide requires chaperone proteins for its intracellular transport to degradation, a process that requires fatty acid-binding proteins (FABPs).

Antidepressant activity of pharmacological and genetic deactivation of the small-conductance calcium-activated potassium channel subtype-3.

Rationale: The voltage-insensitive, small-conductance calcium-activated potassium (SK) channel is a key regulator of neuronal depolarization and is implicated in the pathophysiology of depressive disorders.

Objective: We ascertained whether the SK channel is impaired in the chronic unpredictable stress (CUS) model and whether it can serve as a molecular target of antidepressant action.

Methods: We assessed the depressive-like behavioral phenotype of CUS-exposed rats and performed post-mortem SK channel binding and activity-dependent zif268 mRNA analyses on their brains.

Prenatal Cannabinoid Exposure: Emerging Evidence of Physiological and Neuropsychiatric Abnormalities.

Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing global legalization and the overall perceptions of safety, even during pregnancy. These trends are further compounded by a lack of evidence-based policy and guidelines for prenatal cannabis use, which has led to inconsistent messaging by healthcare providers and medically licensed cannabis dispensaries regarding prenatal cannabis use for treatment of symptoms, such as nausea.

Ethanol-induced changes in synaptic amino acid neurotransmitter levels in the nucleus accumbens of differentially sensitized mice.

Rationale: Ethanol-induced behavioural sensitization (EBS) does not occur uniformly in mice exposed to the sensitization paradigm. This suggests innate differential responses to ethanol (EtOH) in the reward circuitry of individual animals.

Objectives: To better characterize the adaptive differences between low-sensitized (LS) and high-sensitized (HS) mice, we examined excitatory amino acid (EAA) and inhibitory amino acid (IAA) neurotransmitter levels in the nucleus accumbens (NAc) during EBS expression.

xCT knockdown in human breast cancer cells delays onset of cancer-induced bone pain.

Cancers in the bone produce a number of severe symptoms including pain that compromises patient functional status, quality of life, and survival. The source of this pain is multifaceted and includes factors secreted from tumor cells. Malignant cells release the neurotransmitter and cell-signaling molecule glutamate via the oxidative stress-related cystine/glutamate antiporter, system x, which reciprocally imports cystine for synthesis of glutathione and the cystine/cysteine redox cycle.

Evaluation of a novel radiotracer for positron emission tomography imaging of reactive oxygen species in the central nervous system.

Introduction: Few, if any, radiotracers are available for the in vivo imaging of reactive oxygen species (ROS) in the central nervous system. ROS play a critical role in normal cell processes such as signaling and homeostasis but overproduction of ROS is implicated in several disorders. We describe here the radiosynthesis and initial ex vivo and in vivo evaluation of [C]hydromethidine ([C]HM) as a radiotracer to image ROS using positron emission tomography (PET).

Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression.

Despite the lack of robust evidence of effectiveness, current treatment options for cancer-induced depression (CID) are limited to those developed for non-cancer related depression. Here, anhedonia-like and coping behaviours were assessed in female BALB/c mice inoculated with 4T1 mammary carcinoma cells. The behavioural effects of orally administered sulfasalazine (SSZ), a system x inhibitor, were compared with fluoxetine (FLX).

Chronic Inhibition of STAT3/STAT5 in Treatment-Resistant Human Breast Cancer Cell Subtypes: Convergence on the ROS/SUMO Pathway and Its Effects on xCT Expression and System xc- Activity.

Pharmacologically targeting activated STAT3 and/or STAT5 has been an active area of cancer research. The cystine/glutamate antiporter, system xc-, contributes to redox balance and export of intracellularly produced glutamate in response to up-regulated glutaminolysis in cancer cells. We have previously shown that blocking STAT3/5 using the small molecule inhibitor, SH-4-54, which targets the SH2 domains of both proteins, increases xCT expression, thereby increasing system xc- activity in human breast cancer cells.

Overview of Glutamatergic Dysregulation in Central Pathologies.

As the major excitatory neurotransmitter in the mammalian central nervous system, glutamate plays a key role in many central pathologies, including gliomas, psychiatric, neurodevelopmental, and neurodegenerative disorders. Post-mortem and serological studies have implicated glutamatergic dysregulation in these pathologies, and pharmacological modulation of glutamate receptors and transporters has provided further validation for the involvement of glutamate. Furthermore, efforts from genetic, in vitro, and animal studies are actively elucidating the specific glutamatergic mechanisms that contribute to the aetiology of central pathologies.

Depressive-like behaviours and decreased dendritic branching in the medial prefrontal cortex of mice with tumors: A novel validated model of cancer-induced depression.

Depression is commonly comorbid in cancer patients and has detrimental effects on disease progression. Evidence suggests that biological mechanisms may induce the onset of cancer-induced depression (CID). The present investigation aims to establish a validated preclinical animal model of CID.

Cancer-induced oxidative stress and pain.

Cancer pain is a well-documented and prevalent healthcare problem, with current treatment strategies often failing to achieve acceptable efficacy. One of the major difficulties in treating cancer pain owes to the complex interplay between the cancer microenvironment, cancer therapy, and the body's own responses to these biochemical changes. A better understanding of the molecular pathways of nociception that are activated during cancer progression and treatment is necessary for better pain management and increased quality of life.

Olanzapine-induced weight gain in patients with bipolar I disorder: a meta-analysis.

Objective: The weight impact produced by the atypical antipsychotic olanzapine has been explored in meta-analyses focusing on patients with schizophrenia. However, outcomes identified for schizophrenia patients cannot always be generalized to patients with bipolar disorder. This study aims to quantitatively estimate the impact of olanzapine on the weight of patients with bipolar disorder.