Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease

The endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer's disease (AD). However, the association between CB1 alterations and the development of AD neuropathology is unclear and often contradictory. In this study, brain CB1 mRNA and CB1 protein levels were analyzed in 3 × Tg-AD mice and compared to wild-type littermates at 2, 6 and 12 months of age, using in-situ hybridization and immunohistochemistry, respectively. Semiquantitative analysis of CB1 expression focused on the prefrontal cortex (PFC), prelimbic cortex, dorsal hippocampus (DH), basolateral amygdala complex (BLA), and ventral hippocampus (VH), all areas with high CB1 densities that are strongly affected by neuropathology in 3 × Tg-AD mice. At 2 months of age, there was no change in CB1 mRNA and protein levels in 3 × Tg-AD mice compared to Non-Tg mice in all brain areas analyzed. However, at 6 and 12 months of age, CB1 mRNA levels were significantly higher in PFC, DH, and BLA, and lower in VH in 3 × Tg-AD mice compared to wild-type littermates. CB1 immunohistochemistry revealed that CB1 protein expression was unchanged in 3 × Tg-AD at 2 and 6 months of age, while a significant decrease in CB1 receptor immunoreactivity was detected in the BLA and DH of 12-month-old 3 × Tg-AD mice, with no sign of alteration in other brain areas. The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD

Opsin evolution in the Ambulacraria

Opsins - G-protein coupled receptors involved in photoreception - have been extensively studied in the animal kingdom. The present work provides new insights into opsin-based photoreception and photoreceptor cell evolution with a first analysis of opsin sequence data for a major deuterostome clade, the Ambulacraria. Systematic data analysis, including for the first time hemichordate opsin sequences and an expanded echinoderm dataset, led to a robust opsin phylogeny for this cornerstone superphylum. Multiple genomic and transcriptomic resources were surveyed to cover each class of Hemichordata and Echinodermata. In total, 119 ambulacrarian opsin sequences were found, 22 new sequences in hemichordates and 97 in echinoderms (including 67 new sequences). We framed the ambulacrarian opsin repertoire within eumetazoan diversity by including selected reference opsins from non-ambulacrarians. Our findings corroborate the presence of all major ancestral bilaterian opsin groups in Ambulacraria. Furthermore, we identified two opsin groups specific to echinoderms. In conclusion, a molecular phylogenetic framework for investigating light-perception and photobiological behaviors in marine deuterostomes has been obtained

Physical Processes in Star Formation

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00693-8.Star formation is a complex multi-scale phenomenon that is of significant importance for astrophysics in general. Stars and star formation are key pillars in observational astronomy from local star forming regions in the Milky Way up to high-redshift galaxies. From a theoretical perspective, star formation and feedback processes (radiation, winds, and supernovae) play a pivotal role in advancing our understanding of the physical processes at work, both individually and of their interactions. In this review we will give an overview of the main processes that are important for the understanding of star formation. We start with an observationally motivated view on star formation from a global perspective and outline the general paradigm of the life-cycle of molecular clouds, in which star formation is the key process to close the cycle. After that we focus on the thermal and chemical aspects in star forming regions, discuss turbulence and magnetic fields as well as gravitational forces. Finally, we review the most important stellar feedback mechanisms.Peer reviewedFinal Accepted Versio

Nitric oxide synthase in crayfish walking leg ganglia: Segmental differences in chemo-tactile centers argue against a generic role in sensory integration

Nitric oxide (NO) is a diffusible signaling molecule with evolutionarily conserved roles in neural plasticity. Prominent expression of NO synthase (NOS) in the primary olfactory centers of mammals and insects lead to the notion of a special role for NO in olfaction. In insects, however, NOS is also strongly expressed in non-olfactory chemo-tactile centers of the thoracic nerve cord. The functional significance of this apparent association with various sensory centers is unclear, as is the extent to which it occurs in other arthropods. We therefore investigated the expression of NOS in the pereopod ganglia of crayfish (Pacifastacus lenisculus and Procambarus clarkii). Conventional NADPH diaphorase (NADPHd) staining after formaldehyde fixation gave poor anatomic detail, whereas fixation in methanol/formalin (MF-NADPHd) resulted in Golgi-like staining, which was supported by immunohistochemistry using NOS antibodies that recognize a 135-kDa protein in crayfish. MF-NADPHd revealed an exceedingly dense innervation of the chemo-tactile centers. As in insects, this innervation was provided by a system of prominent intersegmental neurons. Superimposed on a putatively conserved architecture, however, were pronounced segmental differences. Strong expression occurred only in the anterior three pereopod ganglia, correlating with the presence of claws on pereopods one to three. These clawed pereopods, in addition to their role in locomotion, are crucially involved in feeding, where they serve both sensory and motor functions. Our findings indicate that strong expression of NOS is not a universal feature of primary sensory centers but instead may subserve a specific requirement for sensory plasticity that arises only in particular behavioral contexts

The development and neuronal complexity of bipinnaria larvae of the sea star <i>Asterias ruben</i>

Free-swimming planktonic larvae are a key stage in the development of many marine phyla, and studies of these organisms have contributed to our understanding of major genetic and evolutionary processes. Although transitory, these larvae often attain a remarkable degree of tissue complexity, with well-defined musculature and nervous systems. Among the best studied are larvae belonging to the phylum Echinodermata, but with work largely focused on the pluteus larvae of sea urchins (class Echinoidea). The greatest diversity of larval strategies among echinoderms is found in the class Asteroidea (sea stars), organisms that are rapidly emerging as experimental systems for genetic and developmental studies. However, the bipinnaria larvae of sea stars have only been studied in detail in a small number of species and although they have been relatively well described neuro-anatomically, they are poorly understood neurochemically. Here, we have analyzed embryonic development and bipinnaria larval anatomy in the common North Atlantic sea star Asterias rubens, using a variety of staining methods in combination with confocal microscopy. Importantly, the chemical complexity of the nervous system of bipinnaria larvae was revealed through use of a diverse set of antibodies, with identification of at least three centers of differing neurochemical signature within the previously described nervous system: the anterior apical organ, oral region, and ciliary bands. Furthermore, the anatomy of the musculature and sites of cell division in bipinnaria larvae was analyzed. Comparisons of developmental progression and molecular anatomy across the Echinodermata provided a basis for hypotheses on the shared evolutionary and developmental processes that have shaped this group of animals. We conclude that bipinnaria larvae appear to be remarkably conserved across ∼200 million years of evolutionary time and may represent a strong evolutionary and/or developmental constraint on species utilizing this larval strategy

The mutable collagenous tissue of echinoderms: from biology to biomedical applications

The mutable collagenous tissue (MCT) of echinoderms (starfish, sea-urchins and their close relations) has the capacity to drastically alter its mechanical properties within a timescale of seconds under the control of the nervous system. MCT is of central importance to the biology of echinoderms: postural fixation of the body or its appendages depends on passive MCT stiffening, and all autotomy (defensive self-detachment) mechanisms involve irreversible MCT destabilisation. This chapter reviews research on the biology and biomedical applications of MCT. It focuses on recent advances in knowledge of its organisation, biomechanics, molecular mechanisms of tensile change and neural control and demonstrates that MCT has attracted interest as a source of constituents for the construction of novel materials with potential biomedical applications and as a source of inspiration for the design of entirely artificial materials with adaptable and controllable mechanical properties

A possible structural correlate of learning performance on a colour discrimination task in the brain of the bumblebee

Synaptic plasticity is considered to be a basis for learning and memory. However, the relationship between synaptic arrangements and individual differences in learning and memory is poorly understood. Here, we explored how the density of microglomeruli (synaptic complexes) within specific regions of the bumblebee (Bombus terrestris) brain relates to both visual learning and inter-individual differences in learning and memory performance on a visual discrimination task. Using whole-brain immunolabelling, we measured the density of microglomeruli in the collar region (visual association areas) of the mushroom bodies of the bumblebee brain. We found that bumblebees which made fewer errors during training in a visual discrimination task had higher microglomerular density. Similarly, bumblebees that had better retention of the learned colour-reward associations two days after training had higher microglomerular density. Further experiments indicated experience-dependent changes in neural circuitry: learning a colour-reward contingency with 10 colours (but not two colours) does result, and exposure to many different colours may result, in changes to microglomerular density in the collar region of the mushroom bodies. These results reveal the varying roles that visual experience, visual learning and foraging activity have on neural structure. Although our study does not provide a causal link between microglomerular density and performance, the observed positive correlations provide new insights for future studies into how neural structure may relate to inter-individual differences in learning and memory

Nervous system and arm regeneration in crinoids

The crinoid Antedon mediterranea has remarkable regeneration abilities, making it a valuable model for the study of these post-embryonic developmental phenomena. Indeed, it can rapidly and completely regenerate arms, pinnules, cirri and the visceral mass, after autotomy or experimentally induced amputations. During regeneration a variety of neural regulatory molecules (neurotransmitters, neuropeptides and growth factors) are thought to play important signalling roles. Here we have analysed the ultrastructural features and some molecular aspects of the nervous system of A. mediterranea in normal and regenerating arms. Animals were collected from Baia delle Grazie in the Gulf of La Spezia (Ligurian Sea, Italy) and maintained in artificial sea-water. Experimental amputations were carried out mimicking natural conditions and regeneration was examined at early (72h post-amputation (pa)) and advanced stages (up to 4 weeks pa). Some tissue samples were processed for standard histological and ultrastructural studies whereas others were prepared for analysis of neuropeptide expression using mRNA in situ hybridization and immunocytochemical techniques. In crinoid arms the main nervous component is the brachial nerve formed by a medulla mainly composed of neural processes and sparse chains of perikarya and an external cortex of perikarya. There is also some evidence of well-defined groups of perikarya at the level of muscle and ligament innervation, that could potentially be considered as a basic form of ganglia thus hypothetically suggesting metamerism of the nervous system. However, this \u201cperikarya clustering\u201d needs to be confirmed by further studies. In the early regenerative phase, the nerve has not yet fully regrown within the regenerate but a continuity can be observed between chains of nervous cells and the undifferentiated cells filling the blastema that is the characteristic structure of this phase. The advanced regenerative phase is characterized by the regeneration of the brachial nerve and the progressive differentiation of other tissues. Analysis of A. mediterranea transcriptome sequence data has enabled identification of transcripts encoding precursors of a variety of neuropeptides (SALMFamides, calcitonin-type, vasopressin-type) and on-going studies are investigating the expression of these and other neuropeptides, which will provide a basis for investigation of the physiological roles of neuropeptides in both non-regenerating and regenerating arms