Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.

Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects.

Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH.

Non-alcoholic steatohepatitis (NASH) has emerged as a major challenge for public health because of high global prevalence and lack of evidence-based therapies. Most animal models of NASH lack sufficient validation regarding disease progression and pharmacological treatment. The Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mouse demonstrate clinical translatability with respect to disease etiology and hallmarks of NASH.

Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3.

Serotonin 2A receptors (5-HTRs) mediate the hallucinogenic effects of psychedelic drugs and are a key target of the leading class of medications used to treat psychotic disorders. These findings suggest that dysfunction of 5-HTRs may contribute to the symptoms of schizophrenia, a mental illness characterized by perceptual and cognitive disturbances. Indeed, numerous studies have found that 5-HTRs are reduced in the brains of individuals with schizophrenia.

Automated Image Analyses of Glomerular Hypertrophy in a Mouse Model of Diabetic Nephropathy.

Background: Glomerular hypertrophy is a hallmark of kidney injury in metabolically induced renal diseases such as obesity-associated glomerulopathies and diabetic nephropathy (DN).

Methods: Using light sheet fluorescent microscopy (LSFM) and 3D image analysis, we tested algorithms for automated and unbiased quantification of total glomerular numbers and individual glomerular volume in the uninephrectomized (UNx) db/db mouse model of DN.

Results: At 6 weeks after surgery, db/db and UNx db/db mice showed increased urine albumin-to-creatinine ratio (ACR) compared with db/+ control mice.

Paroxetine blunts the corticosterone response to swim-induced stress and increases depressive-like behavior in a rat model of postpartum depression.

Perinatal depression (PND) affects 15% of women. During the perinatal period both stress- and gonadal hormones fluctuate widely. Putatively, these fluctuations are involved in PND disease mechanisms.

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study.

Background: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention.

Changes in RFamide-related peptide-1 (RFRP-1)-immunoreactivity during postnatal development and the estrous cycle.

GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3.

Disparate changes in kisspeptin and neurokinin B expression in the arcuate nucleus after sex steroid manipulation reveal differential regulation of the two KNDy peptides in rats.

Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently recognized as important elements for the generation of GnRH pulses. However, the topographic distribution of these peptides and their regulated expression by sex steroids are still not well understood. In this study, detailed examination of NKB and kisspeptin immunoreactivity in the rat ARC was carried out, including comparison between sexes, with and without sex steroid replacement.

Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle regularity, and kisspeptin expression in female rats.

Kisspeptin, encoded by Kiss1, plays a key role in pubertal maturation and reproduction as a positive upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis. To examine the role of high-fat diet (HFD) on puberty onset, estrous cycle regularity, and kisspeptin expression, female rats were exposed to HFD in distinct postnatal periods. Three groups of rats were exposed to HFD containing 60% energy from fat during the pre-weaning period (postnatal day (PND) 1-16, HFD PND 1-16), post-weaning period (HFD PND 21-34), or during both periods (HFD PND 1-34).

Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat.

Tesofensine is a triple monoamine reuptake inhibitor which inhibits noradrenaline, 5-HT and dopamine reuptake. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong and sustained effects in obesity management is not clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity.

The effect of perinatal exposure to ethinyl oestradiol or a mixture of endocrine disrupting pesticides on kisspeptin neurons in the rat hypothalamus.

Early life exposure to endocrine disruptors is considered to disturb normal development of hormone sensitive parameters and contribute to advanced puberty and reduced fecundity in humans. Kisspeptin is a positive regulator of the hypothalamic-pituitary-gonadal axis, and plays a key role in the initiation of puberty. In the adult, Kiss1 gene expression occurs in two hypothalamic nuclei, namely the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), which are differentially regulated by peripheral sex steroid hormones.

Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice.

Kiss1 mRNA and its corresponding peptide products, kisspeptins, are expressed in two restricted brain areas of rodents, the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC). The concentration of mature kisspeptins may not directly correlate with Kiss1 mRNA levels, because mRNA translation and/or posttranslational modification, degradation, transportation and release of kisspeptins could be regulated independently of gene expression, and there may thus be differences in kisspeptin expression even in species with similar Kiss1 mRNA profiles. We measured and compared kisspeptin-immunoreactivity in both nuclei and both sexes of rats and mice and quantified kisspeptin-immunoreactive nerve fibers.