The endocannabinoid system in anxiety, fear memory and habituation.

Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations.

The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment.

Background: Cannabinoids are known to reduce intestinal inflammation. Atypical cannabinoids produce pharmacological effects via unidentified targets. We were interested in whether the atypical cannabinoid O-1602, reportedly an agonist of the putative cannabinoid receptor GPR55, reduces disease severity of dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6N and CD1 mice.

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.

Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus.

Examining the coupling of carbon and nitrogen cycles in Appalachian streams: the role of dissolved organic nitrogen.

Although regional and global models of nitrogen (N) cycling typically focus on nitrate, dissolved organic nitrogen (DON) is the dominant form of nitrogen export from many watersheds and thus the dominant form of dissolved N in many streams. Our understanding of the processes controlling DON export from temperate forests is poor. In pristine systems, where biological N limitation is common, N contained in recalcitrant organic matter (OM) can dominate watershed N losses.

The "AIDS and MDGs" approach: what is it, why does it matter, and how do we take it forward?

Progress towards the Millennium Development Goals (MDGs) has been mixed, and many observers have noted the tendency for development actors to address individual MDGs largely in isolation from one another. This in turn has resulted in missed opportunities to catalyse greater interdisciplinary collaboration and innovation towards MDG achievement. The term 'AIDS and MDGs' is gaining currency as an approach that aims to explore, strengthen and leverage the links between AIDS and other health and development issues.

Focus group findings for the self-report safe driving behaviour measure.

Background: Older adults, family members, and professionals may benefit from a safe driving behaviour self-/proxy-report.

Purpose: During development of the Safe Driving Behavior Measure (SDBM), we conducted focus groups to (1) generate items based on respondents' driving experiences, and (2) obtain SDBM item-refinement feedback.

Methods: Twenty-three older drivers (mean age 70.

Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.

Cannabinoid CB1 receptors (CB1Rs) regulate the neurodegenerative damage of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R stimulation exerts protective effects is still unclear. Here we show that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice.

Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability.

Rubinstein-Taybi syndrome (RSTS) is an inheritable disease associated with mutations in the gene encoding the CREB (cAMP response element-binding protein)-binding protein (CBP) and characterized by growth impairment, learning disabilities, and distinctive facial and skeletal features. Studies in mouse models for RSTS first suggested a direct role for CBP and histone acetylation in cognition and memory. Here, we took advantage of the genetic tools for generating mice in which the CBP gene is specifically deleted in postmitotic principal neurons of the forebrain to investigate the consequences of the loss of CBP in the adult brain.

Concerted action of CB1 cannabinoid receptor and deleted in colorectal cancer in axon guidance.

Endocannabinoids (eCBs) are retrograde neurotransmitters that modulate the function of many types of synapses. The presence of eCBs, their CB1 receptor (CB1R), and metabolizing enzymes at embryonic and early postnatal periods have been linked to developmental processes such as neuronal proliferation, differentiation, and migration, axon guidance, and synaptogenesis. Here, we demonstrate the presence of a functional eCB system in the developing visual system and the role of CB1R during axon growth and retinothalamic development.

AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.

The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA)-induced hippocampal pathogenesis.

Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses.

Endocannabinoids are potent regulators of synaptic strength. They are generally thought to modify neurotransmitter release through retrograde activation of presynaptic type 1 cannabinoid receptors (CB1Rs). In the cerebellar cortex, CB1Rs regulate several forms of synaptic plasticity at synapses onto Purkinje cells, including presynaptically expressed short-term plasticity and, somewhat paradoxically, a postsynaptic form of long-term depression (LTD).

Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections.

A role for endocannabinoid signaling in neuronal morphogenesis as the brain develops has recently been suggested. Here we used the developing somatosensory circuit as a model system to examine the role of endocannabinoid signaling in neural circuit formation. We first show that a deficiency in cannabinoid receptor type 1 (CB(1)R), but not G-protein-coupled receptor 55 (GPR55), leads to aberrant fasciculation and pathfinding in both corticothalamic and thalamocortical axons despite normal target recognition.

Short-term adaptation of conditioned fear responses through endocannabinoid signaling in the central amygdala.

The cannabinoid receptor type 1 (CB1) and the central nucleus of the amygdala (CeA) are both known to have crucial roles in the processing of fear and anxiety, whereby they appear to be especially involved in the control of fear states. However, in contrast to many other brain regions including the cortical subregions of the amygdala, the existence of CB1 in the CeA remains enigmatic. In this study we show that CB1 is expressed in the CeA of mice and that CB1 in the CeA mediates short-term synaptic plasticity, namely depolarization-induced suppression of excitation (DSE) and inhibition (DSI).

Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.

Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models.

A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents.

Background And Purpose: Cannabinoid CB(1) receptor antagonists reduce food intake and body weight, but clinical use in humans is limited by effects on the CNS. We have evaluated a novel cannabinoid antagonist (AM6545) designed to have limited CNS penetration, to see if it would inhibit food intake in rodents, without aversive effects.

Experimental Approach: Cannabinoid receptor binding studies, cAMP assays, brain penetration studies and gastrointestinal motility studies were carried out to assess the activity profile of AM6545.

Prediction of resultant testosterone concentrations from flywheel-based resistive exercise.

Introduction: Numerous variables impact resultant testosterone concentrations (TC) that foretell the efficacy of workouts. Identifying variables may aid the development of in-flight exercise prescription.

Methods: To identify variables that predict the variance in TC from flywheel ergometer exercise, 17 subjects did 3 workouts in a randomized order.

Chemical signal amplification in two-dimensional paper networks.

Two-dimensional paper networks (2DPNs) hold great potential for extending the utility of paper-based chemical and biochemical diagnostics at a cost and ease-of-use that is comparable to conventional lateral flow strips. 2DPNs enable the automated sequential delivery of multiple reagents to a detection region with a single user activation step, and therefore have the potential to extend the processing capabilities of inexpensive paper-based assays with comparable ease of use to conventional lateral flow tests. In this communication, we used a simple 3 inlet 2DPN to perform signal amplification of a colloidal gold label using a gold enhancement solution, thus demonstrating the capability of 2DPNs to perform processes that can improve limits of detection.

Rethinking intervention strategies in stroke family caregiving.

Stroke is a condition that affects both patients and family members who provide care and support. Because stroke is an unexpected traumatic event that suddenly forces family members into a caregiving role, caregivers often experience an overwhelming sense of burden, depression, and isolation; a decline in physical and mental health; and reduced quality of life. Caregiver health is inextricably linked to a stroke survivor's physical, cognitive, and psychological recovery.

Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks.

Conventional microfluidic devices typically require highly precise pumps or pneumatic control systems, which add considerable cost and the requirement for power. These restrictions have limited the adoption of microfluidic technologies for point-of-care applications. Paper networks provide an extremely low-cost and pumpless alternative to conventional microfluidic devices by generating fluid transport through capillarity.

Visualization and measurement of flow in two-dimensional paper networks.

The two-dimensional paper network (2DPN) is a versatile new microfluidic format for performing complex chemical processes. For chemical detection, for example, 2DPNs have the potential to exceed the capabilities and performance of existing paper-based lateral flow devices at a comparable cost and ease of use. To design such 2DPNs, it is necessary to predict 2D flow patterns and velocities within them, but because of the scattering of the paper matrix, conventional particle imaging velocimetry is not practical.

Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice.

The endocannabinoid system is involved in the regulation of gastrointestinal (GI) motility and inflammation. Using the peripherally restricted cannabinoid (CB)(1)/CB(2) receptor agonist naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), we investigated the role of peripheral cannabinoid receptors in the regulation of GI motility and the development of colitis in mice. The actions of SAB378 on whole gut transit, upper GI transit, colonic propulsion, and locomotor activity were investigated in C57BL/6N, CB(1) receptor knockout, and CB(2) receptor knockout mice.

The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice.

Hemopressin is a short, nine amino acid peptide (H-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His-OH) isolated from rat brain that behaves as an inverse agonist at the cannabinoid receptor CB(1), and is shown here to inhibit agonist-induced receptor internalization in a heterologous cell model. Since this peptide occurs naturally in the rodent brain, we determined its effect on appetite, an established central target of cannabinoid signaling. Hemopressin dose-dependently decreases night-time food intake in normal male rats and mice, as well as in obese ob/ob male mice, when administered centrally or systemically, without causing any obvious adverse side effects.

Alterations in the hippocampal endocannabinoid system in diet-induced obese mice.

The endocannabinoid (eCB) system plays central roles in the regulation of food intake and energy expenditure. Its alteration in activity contributes to the development and maintenance of obesity. Stimulation of the cannabinoid receptor type 1 (CB(1) receptor) increases feeding, enhances reward aspects of eating, and promotes lipogenesis, whereas its blockade decreases appetite, sustains weight loss, increases insulin sensitivity, and alleviates dysregulation of lipid metabolism.

Item development and validity testing for a self- and proxy report: the safe driving behavior measure.

Objective: We report on item development and validity testing of a self-report older adult safe driving behaviors measure (SDBM).

Method: On the basis of theoretical frameworks (Precede-Proceed Model of Health Promotion, Haddon's matrix, and Michon's model), existing driving measures, and previous research and guided by measurement theory, we developed items capturing safe driving behavior. Item development was further informed by focus groups.