PAC1 Agonist Maxadilan Reduces Atherosclerotic Lesions in Hypercholesterolemic ApoE-Deficient Mice.

A possible involvement of immune- and vasoregulatory PACAP signaling at the PAC1 receptor in atherogenesis and plaque-associated vascular inflammation has been suggested. Therefore, we tested the PAC1 receptor agonist Maxadilan and the PAC1 selective antagonist M65 on plaque development and lumen stenosis in the ApoE atherosclerosis model for possible effects on atherogenesis. Adult male ApoE mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treated with Maxadilan, M65 or Sham.

Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control.

Background: Kisspeptin (KP) signaling in the brain is defined by the anatomical distribution of KP-producing neurons, their fibers, receptors, and connectivity. Technological advances have prompted a re-evaluation of these chemoanatomical aspects, originally studied in the early years after the discovery of KP and its receptor We have previously characterized(1) seven KP neuronal populations in the mouse brain at the mRNA level, including two novel populations, and examined their short-term response to gonadectomy.

Methods: In this study, we mapped KP fiber distribution in rats and mice using immunohistochemistry under intact and short- and long-term post-gonadectomy conditions.

Comprehensive chemotyping, and the gonadal regulation, of seven kisspeptinergic neuronal populations in the mouse brain.

Background: Kisspeptinergic signaling is well-established as crucial for regulation of reproduction, but its potential broader role in brain function is less understood. This study investigates the distribution and chemotyping of kisspeptin-expressing neurons within the mouse brain.

Methods: RNAscope singleplex, duplex and multiplex in situ hybridization methods were used to assess kisspeptin mRNA (Kiss1) expression and its co-expression with other neuropeptides, excitatory and inhibitory neurotransmitter markers, and sex steroid receptors in intact and gonadectomized young adult mice.

The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation.

The MAP kinase ERK is important for neuronal plasticity underlying associative learning, yet specific molecular pathways for neuronal ERK activation are undetermined. RapGEF2 is a neuron-specific cAMP sensor that mediates ERK activation. We investigated whether it is required for cAMP-dependent ERK activation leading to other downstream neuronal signaling events occurring during associative learning, and if RapGEF2-dependent signaling impairments affect learned behavior.

PAC1 deficiency reduces chondrogenesis in atherosclerotic lesions of hypercholesterolemic ApoE-deficient mice.

Background: Induction of chondrogenesis is associated with progressive atherosclerosis. Deficiency of the ADCYAP1 gene encoding pituitary adenylate cyclase-activating peptide (PACAP) aggravates atherosclerosis in ApoE deficient (ApoE) mice. PACAP signaling regulates chondrogenesis and osteogenesis during cartilage and bone development.