Protective role of neuronal and lymphoid cannabinoid CB receptors in neuropathic pain.

Cannabinoid CB receptor (CB) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB; however, the involvement of CB from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB agonist JWH133 in wild-type and knockout mice lacking CB in neurons, monocytes or constitutively.

Analysis of quantitative trait loci in mice suggests a role of Enoph1 in stress reactivity.

Significant progress in elucidating the genetic etiology of anxiety and depression has been made during the last decade through a combination of human and animal studies. In this study, we aimed to discover genetic loci linked with anxiety as well as depression in order to reveal new candidate genes. Therefore, we initially tested the behavioral sensitivity of 543 F2 animals derived from an intercross of C57BL/6J and C3H/HeJ mice in paradigms for anxiety and depression.

Involvement of the primate specific gene G72 in schizophrenia: From genetic studies to pathomechanisms.

Schizophrenia is a human mental disorder that affects an individual's thoughts, perception, affect and behavior, which is caused by a complex interaction of genetic and environmental factors. Genetic studies have implicated the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in the etiology of schizophrenia and other psychiatric disorders. This gene encodes the protein LG72, which has been discussed as a modulator of the peroxisomal enzyme d-amino-acid-oxidase (DAO), or, alternatively as a mitochondrial protein.

CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells.

Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction.

N-acetyl cysteine treatment rescues cognitive deficits induced by mitochondrial dysfunction in G72/G30 transgenic mice.

Genetic studies have implicated the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in psychiatric diseases. This gene encodes the protein LG72 that has been discussed to function as a putative activator of the peroxisomal enzyme D-amino-acid-oxidase (DAO) and as a mitochondrial protein. We recently generated 'humanized' bacterial artificial chromosome transgenic mice (G72Tg) expressing G72 transcripts in cells throughout the brain.

Early onset of aging-like changes is restricted to cognitive abilities and skin structure in Cnr1⁻/⁻ mice.

Genetic deletion of the cannabinoid 1 (CB1) receptor leads to an early onset of learning and memory impairment. In the present study we asked whether the lack of CB1 receptors accelerates aging in general or is selective for cognitive functions. We therefore compared the onset and dynamics of age-dependent changes in social memory, locomotor activity, hearing ability, and in the histopathology of peripheral organs between wild-type and Cnr1 knockout (Cnr1(-/-)) mice.

Modulation of alcohol and nicotine responses through the endogenous opioid system.

It has been estimated that more than 80% of alcoholics are also nicotine dependent and that, vice versa, the rate of alcoholism is substantially increased by a factor of 4-10 in the nicotine-dependent population. However, the cause for this very high degree of comorbidity is still largely unknown. At the molecular and cellular level, both drugs have very different mechanisms of action.

Quantitative trait loci contributing to physiological and behavioural ethanol responses after acute and chronic treatment.

The aim of the present study was the identification of gene loci that contribute to the development and manifestation of behaviours related to acute and chronic alcohol exposure, as well as to alcohol withdrawal. For this purpose, we performed a serial behavioural phenotyping of 534 animals from the second filial (F2) generation of a C57BL/6J and C3H/HeJ mice intercross in paradigms with relevance to alcohol dependence. First, ethanol-induced hypothermia was determined in ethanol-naive animals.

Effects of the cannabinoid receptor agonist WIN 55,212-2 on operant behavior and locomotor activity in rats.

Cannabinoids influence the motivational state of a subject and affect motor behavior. In the present study, we examined the acute effects of the cannabinoid (CB) receptor agonist WIN 55,212-2 (WIN) in three different doses (0.6, 1.

Recovery of semantic word processing in global aphasia: a functional MRI study.

One important issue concerning the recovery of higher cognitive functions-such as word comprehension in aphasia-is to what extent impairments can be compensated for by intact parts of the network of areas normally involved in a closely related function ("redundancy recovery"). In a previous functional MRI investigation, we were able to show that left hemispheric redundancy recovery within a distributed system of related lexical-semantic functions was the most probable basis of recovery of comprehension from transcortical sensory aphasia. The question remained, however, whether redundancy recovery may play a more general role in the recovery of comprehension after large left hemispheric lesions and severe aphasia.

Recovery of semantic word processing in transcortical sensory aphasia: a functional magnetic resonance imaging study.

In a previous functional magnetic resonance imaging (fMRI) study with normal subjects, we demonstrated regions related to conceptual-semantic word processing around the first frontal sulcus (BA 9) and the posterior parietal lobe (BA 7/40) in agreement with several previous reports. We had the possibility, using the same fMRI paradigm, to study two consecutive cases with left middle cerebral artery (MCA) infarction (RC and HP) and lesions affecting either solely the pre-frontal (HP) or both the pre-frontal and posterior parietal part of the network activated in normal subjects (RC). Both patients showed transcortical sensory aphasia (TSA) on acute assessment.