Disrupted Ultradian Activity Rhythms and Differential Expression of Several Clock Genes in Interleukin-6-Deficient Mice.

The characteristics of the cycles of activity and rest stand out among the most intensively investigated aspects of circadian rhythmicity in humans and experimental animals. Alterations in the circadian patterns of activity and rest are strongly linked to cognitive and emotional dysfunctions in severe mental illnesses such as Alzheimer's disease (AD) and major depression (MDD). The proinflammatory cytokine interleukin 6 (IL-6) has been prominently associated with the pathogenesis of AD and MDD.

Anhedonic behavior in cryptochrome 2-deficient mice is paralleled by altered diurnal patterns of amygdala gene expression.

Mood disorders are frequently paralleled by disturbances in circadian rhythm-related physiological and behavioral states and genetic variants of clock genes have been associated with depression. Cryptochrome 2 (Cry2) is one of the core components of the molecular circadian machinery which has been linked to depression, both, in patients suffering from the disease and animal models of the disorder. Despite this circumstantial evidence, a direct causal relationship between Cry2 expression and depression has not been established.

STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior.

Experimental evidence suggests a role for the immune system in the pathophysiology of depression. A specific involvement of the proinflammatory cytokine interleukin 6 (IL6) in both, patients suffering from the disease and pertinent animal models, has been proposed. However, it is not clear how IL6 impinges on neurotransmission and thus contributes to depression.

Diurnal oscillation of amygdala clock gene expression and loss of synchrony in a mouse model of depression.

Background: Disturbances in circadian rhythm-related physiological and behavioral processes are frequently observed in depressed patients and several clock genes have been identified as risk factors for the development of mood disorders. However, the particular involvement of the circadian system in the pathophysiology of depression and its molecular regulatory interface is incompletely understood.

Methods: A naturalistic animal model of depression based upon exposure to chronic mild stress was used to induce anhedonic behavior in mice.

Circadian abnormalities in a mouse model of high trait anxiety and depression.

Introduction: Dysregulation of circadian rhythms is a key symptom of mood disorders, including anxiety disorders and depression. Whether the circadian abnormalities observed in depressed patients are cause or consequence of the disease remains elusive. Here we aimed to explore potential disturbances of circadian rhythms in a validated genetic animal model of high trait anxiety and co-morbid depression and examine its molecular correlates.

Cognitive enhancement by SGS742 in OF1 mice is linked to specific hippocampal protein expression.

Cognitive enhancement by the GABA (B) antagonist SGS742 has been reported and we decided to search for proteins involved. Hippocampi from OF1 mice were from SGS742- treated animals and three control groups. Proteins were extracted and run on 2DE, and spots were quantified.

The role of post-translational modifications for learning and memory formation.

Learning and memory depend on molecular mechanisms involving the protein machinery. Recent evidence proposes that post-translational modifications (PTMs) play a major role in these cognitive processes. PTMs including phosphorylation of serine, threonine, and tyrosine are already well-documented to play a role for synaptic plasticity of the brain, neurotransmitter release, vesicle trafficking and synaptosomal or synaptosomal-associated proteins are substrates of a series of specific protein kinases and their counterparts, protein phosphatases.

Modulation of the hippocampal protein machinery in voluntary and treadmill exercising rats.

Information about protein expression studies in the brain of exercising and sedentary animals is limited. Cognitive functions change during exercise and the aim of this study was to investigate rat protein levels of the protein machinery in the hippocampus, the main cognitive brain area for spatial learning and memory, in exercising rats. Protein fluctuations may reflect functional variation during exercise.

Fluctuations of hippocampal neuronal protein levels over the estrous cycle in the rat.

Hippocampal function is known to be estrous-cycle-dependent but information on estrous-cycle-dependent protein expression is limited. It was therefore the aim to study protein levels of the neuronal network over the estrous cycle in the hippocampus of female rats and in males showing protein chemical neuroanatomy in this area. Female and male OFA Sprague-Dawley rats were used and females were grouped to proestrous, estrous, metestrous and diestrous by using vaginal smears.

The hippocampal protein machinery varies over the estrous cycle.

Information about estrous cycle (EC) and sex-dependent protein levels is limited. Cognitive functions vary over the EC and the aim of this study was to investigate rat protein fluctuations in the hippocampus, the main cognitive brain area for learning and memory, in the individual phases of the EC and in males and indeed protein fluctuations may reflect functional variation over the EC. Sprague-Dawley rats were used in the studies and estrous phases were determined.

Mass spectrometrical characterization of NDRG2 protein (N-myc-downstream regulated gene 2) and description of two novel phosphorylation sites.

Antidepressant-related protein (NDRG2) is a member of the N-myc downstream-regulated gene family and a role for differentiation and signaling has been proposed. Performing protein profiling we observed NDRG2 and decided to characterize this important biomolecule. Estrous cycle phases were determined in Sprague-Dawley rats and the hippocampus was taken.

Hippocampal signaling protein levels are different in early and late metestrus in the rat.

Early and late metestrus in the rat differ by progesterone levels. As it is known that progesterone shows a potential negative effect on cognitive performances and can counteract the estradiol-induced neural effects, we intended to study signaling proteins in the hippocampus, a structure representing a main brain area of cognitive function. Female OFA Sprague-Dawley rats were used in the studies and estrous phases were determined using vaginal smears.

Estrous-cycle-dependent hippocampal levels of signaling proteins.

There is information that proteins are expressed in a hormone-dependent manner but no systematic study on this subject has been carried out to the best of our knowledge. We therefore decided to investigate protein expression in a well-studied brain area, the hippocampus, in female rats at various phases of the estrous cycle and in male rats. Male and female OFA Sprague-Dawley rats were used in the studies and estrous phases were determined using vaginal smears and females were grouped according to PE, E, ME, and DE.

Serum, liver, and kidney proteomic analysis for the alloxan-induced type I diabetic mice after insulin gene transfer of naked plasmid through electroporation.

Gene therapy has been reported to be effective in treating diabetes mellitus (DM), while little has been found out about the functional protein changes since. The liver and kidney play important roles in glucose absorption, metabolism, and excretion. Changes in the two organs may reflect pathologic alterations during DM, while the serum has a direct connection with most organs and pathological changes.

Bone loss induced by ovariectomy in rats is prevented by gene transfer of parathyroid hormone or an Arg-Gly-Asp-containing peptide.

Osteoporosis is a major and growing healthcare concern as the population ages. The genes of both a Arg-Gly-Asp (RGD)-containing peptide and parathyroid hormone (PTH) were used to reduce bone loss induced by ovariectomy (OVX) in rats. Plasmids with either RGD or PTH gene were delivered into the quadriceps of OVX rats.

Transfer of a gene containing the Arg-Gly-Asp peptide prolongs the bleeding time of mice.

Peptides containing Arg-Gly-Asp (RGD) have been used to decrease thrombosis by competitive inhibition of the integrin glycoprotein, alphaIIb/beta3a, in platelets. However, they have a short half-life in vivo. A naked plasmid, pCMV-RGD, was transferred into the skeletal muscle of mice and RGD gene expression was observed by RT-PCR.