A Recent Class of Chemosensory Neurons Developed in Mouse and Rat

In most animal species, the vomeronasal organ ensures the individual recognition of conspecifics, a prerequisite for a successful reproduction. The vomeronasal organ expresses several receptors for pheromone detection. Mouse vomeronasal type-2 receptors (V2Rs) are restricted to the basal neurons of this organ and organized in four families. Family-A, B and D (family ABD) V2Rs are expressed monogenically (one receptor per neuron) and coexpress with either Vmn2r1 or Vmn2r2, two members of family-C V2Rs. Thus, basal neurons are characterized by specific combinations of two V2Rs. To investigate this issue, we raised antibodies against all family-C V2Rs and analyzed their expression pattern. We found that six out of seven family-C V2Rs (Vmn2r2-7) largely coexpressed and that none of the anti-Vmn2r2-7 antibodies significantly stained Vmn2r1 positive neurons. Thus, basal neurons are divided into two complementary subsets. The first subset (Vmn2r1-positive) preferentially coexpresses a distinct group of family-ABD V2Rs, whereas the second subset (Vmn2r2-7-positive) coexpresses the remaining group of V2Rs. Phylogenetic reconstruction and the analysis of genetic loci in various species reveal that receptors expressed by this second neuronal subset are recent branches of the V2R tree exclusively present in mouse and rat. Conversely, V2Rs expressed in Vmn2r1 positive neurons, are phylogenetically ancient and found in most vertebrates including rodents. Noticeably, the more recent neuronal subset expresses a type of Major Histocompatibility Complex genes only found in murine species. These results indicate that the expansion of the V2R repertoire in a murine ancestor occurred with the establishment of a new population of vomeronasal neurons in which coexists the polygenic expression of a recent group of family-C V2Rs (Vmn2r2-7) and the monogenic expression of a recent group of family-ABD V2Rs. This evolutionary innovation could provide a molecular rationale for the exquisite ability in individual recognition and mate choice of murine species

Why Can't Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study

The vomiting (emetic) reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus) or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver), Ctenohystrica (guinea pig, nutria), and squirrel-related (mountain beaver) species. Prototypical emetic agents, apomorphine (sc), veratrine (sc), and copper sulfate (ig), failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted). These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew). Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation) compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed. © 2013 Horn et al

Brain MRI of nasal MOG therapeutic effect in relapsing-progressive EAE

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) considered to be a T cell-mediated autoimmune disease. Mucosally administered antigens induce regulatory T cells that secrete anti-inflammatory cytokines at the anatomic site where the mucosally administered Ag is located. We have previously reported in a mouse model of stroke that nasal treatment with MOG35–55 peptide reduces ischemic infarct size and improves behavior, by inducing IL-10-secreting T cells. We have also demonstrated that an experimental autoimmune encephalomyelitis (EAE) model in non-obese diabetic (NOD) mice leads to a relapsing progressive disease and that brain lesions can be visualized noninvasively by magnetic resonance imaging (MRI). Here, we investigated whether nasal treatment with 25 μg of MOG35–55 after the first attack affects clinical progression and MRI outcome in the NOD model. We found that nasal MOG35–55 treatment administered three times after the first attack and then weekly reduced both the peak clinical disease score and clinical score during remission. Pathology revealed less infiltration of cells and reduction in white-matter damage as measured by Luxol blue staining in treated animals. This model is unique in that there are lesions in the corpus callosum, external capsule, fimbria, internal capsule and thalamus, which is analogous to what is observed in MS. MRI of individual animals using fractional anisotropy (FA) and T1-gadolinum (T1-Gd) imaging was able to identify lesions in all of these anatomic areas, and we found lower levels of brain pathology by MRI in treated mice with both methods. Our results indicate a beneficial effect of nasal MOG on relapsing-progressive EAE and demonstrate that non-invasive MRI imaging may be used to monitor treatment of ongoing disease in this model for testing new therapies for MS