Fluoxetine treatment supports predictive validity of the three hit model of depression in male PACAP heterozygous mice and underpins the impact of early life adversity on therapeutic efficacy.

According to the three hit concept of depression, interaction of genetic predisposition altered epigenetic programming and environmental stress factors contribute to the disease. Earlier we demonstrated the construct and face validity of our three hit concept-based mouse model. In the present work, we aimed to examine the predictive validity of our model, the third willnerian criterion.

Corticotropin-Releasing Factor-Producing Cells in the Paraventricular Nucleus of the Hypothalamus and Extended Amygdala Show Age-Dependent FOS and FOSB/DeltaFOSB Immunoreactivity in Acute and Chronic Stress Models in the Rat.

Corticotropin-releasing factor (CRF) immunoreactive (ir) neurons of the paraventricular nucleus of the hypothalamus (PVN) play pivotal role in the coordination of stress response. CRF-producing cells in the central nucleus of amygdala (CeA) and oval division of the bed nucleus of stria terminalis (BNSTov) are also involved in stress adaptation and mood control. Immediate early gene products, subunits of the transcription factor activator protein 1 (AP1) are commonly used as acute (FOS) and/or chronic (FOSB/deltaFOSB) markers for the neuronal activity in stress research.

Both Basal and Acute Restraint Stress-Induced c-Fos Expression Is Influenced by Age in the Extended Amygdala and Brainstem Stress Centers in Male Rats.

The hypothalamus-pituitary-adrenal axis (HPA) is the main regulator of the stress response. The key of the HPA is the parvocellular paraventricular nucleus of the hypothalamus (pPVN) controlled by higher-order limbic stress centers. The reactivity of the HPA axis is considered to be a function of age, but to date, little is known about the background of this age-dependency.

Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background.

Major depression is a common cause of chronic disability. Despite decades of efforts, no equivocally accepted animal model is available for studying depression. We tested the validity of a new model based on the three-hit concept of vulnerability and resilience.

Higher susceptibility of somatostatin 4 receptor gene-deleted mice to chronic stress-induced behavioral and neuroendocrine alterations.

The somatostatin 4 receptor (sst) is widely expressed in stress-related brain areas (e.g. hippocampus, amygdala) and regulates the emotional behavior in acute situations.

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.].

Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers.

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in stress adaptation with potential relevance in mood disorder management. PACAP deficient (KO) mice on CD1 background were shown to have depression-like phenotype. Here we aimed at investigating effects of chronic variable mild stress (CVMS) in non-injected, vehicle and imipramine-treated KO mice vs.

The embryonic pineal gland of the chicken as a model for experimental jet lag.

The circadian clock in the chicken pineal model develops before hatching, at around the 17th embryonic day (ED17). By this stage, it runs in synchrony with environmental cues. To address if phase resetting mechanisms are comparable to those of post-hatched chicken, we investigated ED19 stage chicken embryos under 12h light:12h dark (LD), under constant darkness (DD), or under acute 4h phase delay of the LD condition (LD+4).

Circadian clocks and tumor biology: what is to learn from human skin biopsies?

Some of the components of the circadian molecular clock have been shown to link directly to tumor suppression. Most studies on human tumorous biopsies with consistently down-regulated clock gene expression suggested a protective role for these genes against cancer formation. To highlight some limitations of this hypothesis we review these data in light of recent evidences from animal research, epidemiologic studies, and clinical data on skin tumors.

Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors.

The majority of our genes may be regulated in a daily rhythm, including the genes for cell cycle control. Epidemiological and genetic evidences suggest that disruption of circadian timing mechanisms makes our cells more vulnerable to cancer formation. The aim of this study was to investigate the relationship between expression patterns of circadian clock genes (period homolog (per)1, per2, clock, and cry1) and tumor development by analyzing human skin biopsies of malignant melanoma and nonmalignant naevus tumors.

Sexual dimorphism in the effect of concomitant progesterone administration on changes caused by long-term estrogen treatment in pituitary hormone immunoreactivities of rats.

Background: Since in clinical practice long-term estrogen (E) treatment is frequently applied, our aim was to study the effect of concomitant progesterone (P) administration on changes caused by long-term estrogen treatment in the secretion of LH, FSH, PRL and GH.

Material/methods: Diethylstilbestrol (DES), P or both in silastic capsules were implanted under the skin of prepubertal Sprague-Dawley male and female rats. Animals survived for two or five months.

Expression pattern of clock under acute phase-delay of the light/dark cycle in the chicken pineal model.

Shift workers have a higher risk of metabolic syndrome, a condition that also develops in mice carrying mutation in their circadian clock gene clock. To collect more data on the transcriptional changes of clock under phase-shifted light/dark LD conditions, we examined the 24h patterns of clock mRNA expression in vivo and in vitro in chickens exposed acutely to a reversed LD (DL) cycle. Under controlled LD conditions (lights on at 6:00, lights off at 20:00), clock mRNA expression peaked in vivo at 2:00 (Zeitgeber Time 20, ZT20) and in vitro at 22:00 (ZT16).

Effects of PACAP on the oxidative stress-induced cell death in chicken pinealocytes is influenced by the phase of the circadian clock.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with highly potent neuro- and general cytoprotective actions. PACAP is also an important modulator of circadian rhythmic functions, including time-dependent effects in the pineal gland. It is not known whether PACAP influences the survival of pinealocytes.

Effects of maternal separation on dynamics of urocortin 1 and brain-derived neurotrophic factor in the rat non-preganglionic Edinger-Westphal nucleus.

Although mood disorders are frequently genetically determined and to some degree gender-dependent, the concept of early life 'programming', implying a relation between perinatal environmental events and adult mood disorders, has recently gained considerable attention. In particular, maternal separation (MS) markedly affects various stress-sensitive brain centers. Therefore, MS is considered as a suitable experimental paradigm to study how early life events affect brain plasticity and, hence, cause psychopathologies like major depression.

Expression of Cry2 in the chicken pineal gland: effects of changes in light-dark conditions.

Pineal expression of Cry2 mRNA has been examined in chickens under normal (LD) and reversed (DL) light-dark conditions. In vivo the peak of Cry2 mRNA content at late subjective day under LD diminished after switching to a DL schedule. In vitro, Cry2 mRNA levels showed a steady decrease during light exposure at subjective night.

Circadian expression of clock genes clock and Cry1 in the embryonic chicken pineal gland.

Clock and Cry1 expression were examined in the pineal gland of chicken embryos incubated under constant darkness from embryonic day (ED) 0. From ED13, Clock and Cry1 mRNA levels showed episodic alterations. After ED17, circadian pattern of clock gene expression was seen both in vivo and in vitro.

The in vitro and in ovo effects of environmental illumination and temperature on the melatonin secretion from the embryonic chicken pineal gland.

Pineal glands of chicken embryos were placed into a perifusion system for 4 days. The pineal glands were illuminated or exposed to elevated temperature for 8 or 12 h during the in vitro experiment and/or in ovo. Both daily illumination and repeated elevations of environmental temperature transitionally inhibited melatonin release before, and controlled the phase of melatonin rhythm after, the 17th day of embryonic life (E17).

Effects of PACAP on the circadian changes of signaling pathways in chicken pinealocytes.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of circadian rhythms. In mammals, the brain's biological clock is the suprachiasmatic nucleus, receiving photic information from the retina through the retinohypothalamic pathway, where PACAP is the main cotransmitter of glutamate. The primary conductor of circadian rhythms of birds is the pineal gland.

Stress, geomagnetic disturbance, infradian and circadian sampling for circulating corticosterone and models of human depression?

While certain circadian hormonal changes are prominent, their predictable assessment requires a standardization of conditions of sampling. The 24-hour rhythm in circulating corticosterone of rodents, known since the 1950s, was studied as a presumed proxy for stress on 108 rats divided into 9 groups of 6 male and 9 groups of 6 female animals sampled every 4 hours for 24 hours. In a first stress study, the "no-rhythm" (zero-amplitude) assumption failed to be rejected at the 5% probability level in the two control groups and in 16 out of the 18 groups considered.

The role of PACAP in the control of circadian expression of clock genes in the chicken pineal gland.

Several features of the molecular circadian oscillator of the chicken pineal gland show homology with those in the mammalian SCN. Studies have shown the effects of PACAP on the mammalian SCN, but its effects on the expression of clock genes in the avian pineal gland have not yet been demonstrated. Clock and Cry1 expression was analyzed in pineal glands of chicken embryos after exposure to PACAP-38 in vitro.

The effects of environmental illumination on the in vitro melatonin secretion from the embryonic and adult chicken pineal gland.

The aim of this study was to monitor the changes in the pattern of the in vitro melatonin (MT) secretion under reversed illumination cycles with low intensity of light during photo phase. Although light is known to be one of the major synchronizing factors of the circadian MT rhythm in birds, there are no data available on the limits of direct light sensitivity of the avian pinealocytes. In our experiments, MT secretion from adult or from embryonic chicken pineal glands was monitored in a perifusion system for 4 days.

Cry1 expression in the chicken pineal gland: effects of changes in the light/dark conditions.

Cryptochromes (Cry) are core components in the gene regulation of circadian rhythmic processes. It was shown earlier, that Cry1 mRNA content of the avian pineal gland was increased after a 4h exposure to light during subjective night; however, a 30min exposure was ineffective. In this study, changes in pineal Cry1 expression were detected in chickens during and after being placed into reversed light/dark environment.