Cannabinoid CB receptors mediate the anxiolytic-like effects of monoacylglycerol lipase inhibition in a rat model of predator-induced fear.

The endocannabinoid system is a key regulator of the response to psychological stress. Inhibitors of monoacylglycerol lipase (MGL), the enzyme that deactivates the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), exert anxiolytic-like effects in rodent models via 2-AG-dependent activation of CB cannabinoid receptors. In the present study, we examined whether the MGL inhibitor JZL184 might modulate persistent predator-induced fear in rats, a model that captures features of human post-traumatic stress disorder.

A Multimedia Educational Module for Teaching Early Medical Neuroanatomy.

Introduction: As the global burden of neurological disorders continues to rise, physicians' need for a solid understanding of neuroanatomy is becoming more important. Traditional neuroanatomy curricula offer a limited approach to educating a diverse profile of learning styles. In an attempt to incorporate recent literature addressing diverse learning formats, we developed and evaluated two new image-based resources for the neuroscience curriculum.

Early identification of struggling learners: using prematriculation and early academic performance data.

Introduction: A perennial difficultly for remediation programmes in medical school is early identification of struggling learners so that resources and assistance can be applied as quickly as is practical. Our study investigated if early academic performance has predictive validity above and beyond pre-matriculation variables.

Methods: Using three cohorts of medical students, we used logistic regression modelling and negative binomial regression modelling to assess the strength of the relationships between measures of early academic performance and outcomes-later referral to the academic review and performance committee and total module score.

A Multimedia Dissection Module for Scalp, Meninges, and Dural Partitions.

Introduction: For students beginning their medical education, the neuroscience curriculum is frequently seen as the most difficult, and many express an aversion to the topic. A major reason for this aversion amongst learners is the perceived complexity of neuroanatomy. By means of a video tutorial, this module aims to help students feel confident with the cadaveric dissection and identification of key anatomical structures as well as improve comprehension of associated clinical correlations presented for the scalp, meninges, and dural partitions.

Effects of fatty acid amide hydrolase inhibitor URB597 in a rat model of trauma-induced long-term anxiety.

Rationale: The endocannabinoid neurotransmitter, anandamide, has been implicated in the central modulation of stress responses. Previous animal experiments have shown that inhibitors of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), enhance the ability to cope with acute and chronic stress.

Objectives: Here, we investigated the effects of the globally active FAAH inhibitor URB597 in a rat model of predator stress-induced long-term anxiety.

Network science and the human brain: Using graph theory to understand the brain and one of its hubs, the amygdala, in health and disease.

Over the past 15 years, the emerging field of network science has revealed the key features of brain networks, which include small-world topology, the presence of highly connected hubs, and hierarchical modularity. The value of network studies of the brain is underscored by the range of network alterations that have been identified in neurological and psychiatric disorders, including epilepsy, depression, Alzheimer's disease, schizophrenia, and many others. Here we briefly summarize the concepts of graph theory that are used to quantify network properties and describe common experimental approaches for analysis of brain networks of structural and functional connectivity.

Glucose-Dependent Insulin Secretion in Pancreatic β-Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptors.

Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells requires an increase in intracellular free Ca2+ concentration ([Ca2+]). Glucose uptake into β-cells promotes Ca2+ influx and reactive oxygen species (ROS) generation. In other cell types, Ca2+ and ROS jointly induce Ca2+ release mediated by ryanodine receptor (RyR) channels.

The Anx7(+/-) knockout mutation alters electrical and secretory responses to Ca(2+)-mobilizing agents in pancreatic β-cells.

Insulin secretion from the pancreatic β-cell is controlled by changes in membrane potential and intracellular Ca(2+). The contribution of intracellular Ca(2+) stores to this process is poorly understood. We have previously shown that β-cells of mice lacking one copy of the Annexin 7 gene (Anx7(+/-)) express reduced levels of IP(3) receptors and defects in IP(3)-dependent Ca(2+) signaling.

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components.

Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation.

Glucose-dependent and -independent electrical activity in islets of Langerhans of Psammomys obesus, an animal model of nutritionally induced obesity and diabetes.

Glucose-induced insulin secretion from pancreatic beta-cells involves metabolism-induced membrane depolarization and voltage-dependent Ca(2+) influx. The electrical events in beta-cell glucose sensing have been studied intensely using mouse islets of Langerhans, but data from other species, including models of type 2 diabetes mellitus (T2DM), are lacking. In this work, we made intracellular recordings of electrical activity from cells within islets of the gerbil Psammomys obesus (fat sand rat), a model of dietary-induced T2DM.

Properties of voltage-gated Ca2+ currents measured from mouse pancreatic beta-cells in situ.

We used the single-microelectrode voltage-clamp technique to record ionic currents from pancreatic beta-cells within intact mouse islets of Langerhans at 37 degrees C, the typical preparation for studies of glucose-induced "bursting" electrical activity. Cells were impaled with intracellular microelectrodes, and voltage pulses were applied in the presence of tetraethylammonium. Under these conditions, a voltage-dependent Ca2+ current (I(Cav)), containing L-type and non-L-type components, was observed.

A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo.

One of the hallmarks of type 2 diabetes is that pancreatic beta cells fail to release sufficient amounts of insulin in the presence of elevated blood glucose levels. Insulin secretion is modulated by many hormones and neurotransmitters including acetylcholine, the major neurotransmitter of the peripheral parasympathetic nervous system. The physiological role of muscarinic acetylcholine receptors expressed by pancreatic beta cells remains unclear at present.

Ion channel formation by Alzheimer's disease amyloid beta-peptide (Abeta40) in unilamellar liposomes is determined by anionic phospholipids.

Incorporation of Alzheimer's disease amyloid beta-proteins (AbetaPs) across natural and artificial bilayer membranes leads to the formation of cation-selective channels. To study the peptide-membrane interactions involved in channel formation, we used cation reporter dyes to measure AbetaP-induced influx of Na+, Ca2+, and K+ into liposomes formed from phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylcholine (PC). We found that Abeta40, but not Abeta40-1 or Abeta28, caused a dose-dependent increase in the concentration of each cation in the lumen of liposomes formed from the acidic phospholipids PS and PI.

Regulation of insulin secretion in islets of Langerhans by Ca(2+)channels.

Insulin secretion from beta-cells of the pancreatic islets of Langerhans is triggered by Ca(2+) influx through voltage-dependent Ca(2+) channels. Electrophysiological and molecular studies indicate that beta-cells express several subtypes of these channels. This review discusses their roles in regulating insulin secretion, focusing on recent studies using beta-cells, exogenous expression systems, and Ca(2+) channel knockout mice.

Three roads to islet bursting: emergent oscillations in coupled phantom bursters.

Glucose-induced membrane potential and Ca(2+) oscillations in isolated pancreatic beta-cells occur over a wide range of frequencies, from >6/min (fast) to <1/min (slow). However, cells within intact islets generally oscillate with periods of 10-60 s (medium). The phantom bursting concept addresses how beta-cells can generate such a wide range of frequencies.

Muscarinic stimulation of pancreatic insulin and glucagon release is abolished in m3 muscarinic acetylcholine receptor-deficient mice.

Pancreatic muscarinic acetylcholine receptors play an important role in stimulating insulin and glucagon secretion from islet cells. To study the potential role of the M(3) muscarinic receptor subtype in cholinergic stimulation of insulin release, we initially examined the effect of the muscarinic agonist, oxotremorine-M (Oxo-M), on insulin secretion from isolated pancreatic islets prepared from wild-type (WT) and M(3) receptor-deficient mice (M3(+/-) and M3(-/-) mice). At a stimulatory glucose level (16.

Loperamide mobilizes intracellular Ca2+ stores in insulin-secreting HIT-T15 cells.

1 We have investigated the effects of loperamide on intracellular Ca(2+) stores and membrane K(+) channels in insulin-secreting hamster insulinoma (HIT-T15) cells. 2 In cell-attached patch-clamp mode, loperamide (3-250 micro M) activated large single-channel currents. The loperamide-activated currents were tentatively identified as Ca(2+)-activated K(+) channel (K(Ca)) currents based on their single-channel conductance (145 pS), apparent reversal potential, and insensitivity to tolbutamide.