Comparative Brain Morphology of the Greenland and Pacific Sleeper Sharks and its Functional Implications

In cartilaginous fishes, variability in the size of the brain and its major regions is often associated with primary habitat and/or specific behavior patterns, which may allow for predictions on the relative importance of different sensory modalities. The Greenland (Somniosus microcephalus) and Pacific sleeper (S. pacificus) sharks are the only non-lamnid shark species found in the Arctic and are among the longest living vertebrates ever described. Despite a presumed visual impairment caused by the regular presence of parasitic ocular lesions, coupled with the fact that locomotory muscle power is often depressed at cold temperatures, these sharks remain capable of capturing active prey, including pinnipeds. Using magnetic resonance imaging (MRI), brain organization of S. microcephalus and S. pacificus was assessed in the context of up to 117 other cartilaginous fish species, using phylogenetic comparative techniques. Notably, the region of the brain responsible for motor control (cerebellum) is small and lacking foliation, a characteristic not yet described for any other large-bodied (\u3e3 m) shark. Further, the development of the optic tectum is relatively reduced, while olfactory brain regions are among the largest of any shark species described to date, suggestive of an olfactory-mediated rather than a visually-mediated lifestyle

Enhanced Detection of Desmoplasia By Targeted Delivery of Iron Oxide Nanoparticles To the Tumour-Specific Extracellular Matrix

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide. CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T2-weighted scans and T2 relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter. Larger tumours with significantly reduced tumour blood vessels show a lack of CREKA-IO-NP uptake. Our data suggest CSG-IO-NP are particularly useful for detecting stroma in early and advanced solid tumours

Combined rTMS/fMRI Studies: An Overlooked Resource in Animal Models

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique, which has brain network-level effects in healthy individuals and is also used to treat many neurological and psychiatric conditions in which brain connectivity is believed to be abnormal. Despite the fact that rTMS is being used in a clinical setting and animal studies are increasingly identifying potential cellular and molecular mechanisms, little is known about how these mechanisms relate to clinical changes. This knowledge gap is amplified by non-overlapping approaches used in preclinical and clinical rTMS studies: preclinical studies are mostly invasive, using cellular and molecular approaches, while clinical studies are non-invasive, including functional magnetic resonance imaging (fMRI), TMS electroencephalography (EEG), positron emission tomography (PET), and behavioral measures. A non-invasive method is therefore needed in rodents to link our understanding of cellular and molecular changes to functional connectivity changes that are clinically relevant. fMRI is the technique of choice for examining both short and long term functional connectivity changes in large-scale networks and is becoming increasingly popular in animal research because of its high translatability, but, to date, there have been no reports of animal rTMS studies using this technique. This review summarizes the main studies combining different rTMS protocols with fMRI in humans, in both healthy and patient populations, providing a foundation for the design of equivalent studies in animals. We discuss the challenges of combining these two methods in animals and highlight considerations important for acquiring clinically-relevant information from combined rTMS/fMRI studies in animals. We believe that combining rTMS and fMRI in animal models will generate new knowledge in the following ways: functional connectivity changes can be explored in greater detail through complementary invasive procedures, clarifying mechanism and improving the therapeutic application of rTMS, as well as improving interpretation of fMRI data. And, in a more general context, a robust comparative approach will refine the use of animal models of specific neuropsychiatric conditions

Tracking cognitive changes in new-onset epilepsy : functional imaging challenges

Functional imaging has potential for tracking changes in cognition during the onset and evolution of epilepsy. Although the concept of imaging such changes over time is an exciting new direction, feasibility remains an open question. The current article outlines a case example in which functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) were used to monitor memory changes before and after selective temporal lobe resection. From this example, three key methodologic challenges for new-onset epilepsy are identified and discussed. The first challenge relates to the interpretation of results in regions near epileptogenic tissue. We argue that this is best addressed by collecting information from multiple modalities to test for convergent evidence. The second challenge relates to optimizing the methods for sensitivity to detecting changes. In this case, enhanced imaging methods and a region-of-interest approach provide necessary focus. The third and final challenge relates to the practical difficulties of conducting research in new-onset epilepsy cases. We suggest that greater integration of imaging research within the clinical setting is needed.Peer reviewed: YesNRC publication: Ye

Vitamin D is crucial for maternal care and offspring social behaviour in rats

Early life vitamin D plays a prominent role in neurodevelopment and subsequent brain function, including schizophrenic-like outcomes and increasing evidence for an association with autism spectrum disorder (ASD). Here, we investigate how early life vitamin D deficiency during rat pregnancy and lactation alters maternal care and influences neurodevelopment and affective, cognitive and social behaviours in male adult offspring. Sprague-Dawley rats were placed on either a vitamin D control (2195 IU/kg) or deficient diet (0 IU/kg) for five weeks before timed mating, and diet exposure was maintained until weaning of offspring on postnatal day (PND) 23. MRI scans were conducted to assess brain morphology, and plasma corticosterone levels and neural expression of genes associated with language, dopamine and glucocorticoid exposure were characterised at PND1, PND12 and 4 months of age. Compared to controls, vitamin D-deficient dams exhibited decreased licking and grooming of their pups but no differences in pup retrieval. Offspring neurodevelopmental markers were unaltered, but vitamin D-deficient pup ultrasonic vocalisations were atypical. As adults, males that had been exposed to vitamin D deficiency in early life exhibited decreased social behaviour, impaired learning and memory outcomes and increased grooming behaviour, but unaltered affective behaviours. Accompanying these behavioural changes was an increase in lateral ventricle volume, decreased cortical FOXP2 (a protein implicated in language and communication) and altered neural expression of genes involved in dopamine and glucocorticoid-related pathways. These data highlight that early life levels of vitamin D are an important consideration for maternal behavioural adaptations as well as offspring neuropsychiatry

A late Holocene paleo-productivity record in the western Gulf of Maine, USA, inferred from growth histories of the long-lived ocean quahog (Arctica islandica)

To investigate environmental variability during the late Holocene in the western Gulf of Maine, USA, we collected a 142-year-old living bivalve (Arctica islandica) in 2004, and three fossil A. islandica shells of the Medieval Warm Period (MWP) and late MWP / Little Ice Age (LIA) period (corrected C-14(AMS) = 1030 +/- A 78 ad; 1320 +/- A 45 ad; 1357 +/- A 40 ad) in 1996. We compared the growth record of the modern shell with continuous plankton recorder (CPR) time-series (1961-2003) from the Gulf of Maine. A significant correlation (r (2) = 0.55; p < 0.0001) exists between the standardized annual growth index (SGI) of the modern shell and the relative abundance of zooplankton species Calanus finmarchicus. We therefore propose that SGI data from A. islandica is a valid proxy for paleo-productivity of at least one major zooplankton taxa. SGIs from these shells reveal significant periods of 2-6 years (NAO-like) based on wavelet analysis, multitaper method (MTM) analysis and singular spectrum analysis (SSA) during the late Holocene. Based on established physical oceanographic observation in the Gulf of Maine, we suggest that slope water variability coupled with North Atlantic Oscillation (NAO) dynamics is primarily responsible for the observed SGI variability