A large body of research has been dedicated to understanding the factors that modulate spatial cognition and attributes of the hippocampus, a highly plastic brain region that underlies spatial ...processing abilities. Variation in gonadal hormones impacts spatial memory and hippocampal attributes in vertebrates, although the direction of the effect has not been entirely consistent. To add complexity, individuals in the field must optimize fitness by coordinating activities with the appropriate environmental cues, and many of these behaviors are correlated tightly with seasonal variation in gonadal hormone release. As such, it remains unclear if the relationship among systemic gonadal hormones, spatial cognition, and the hippocampus also exhibits seasonal variation. This review presents an overview of the relationship among gonadal hormones, the hippocampus, and spatial cognition, and how the seasonal release of gonadal hormones correlates with seasonal variation in spatial cognition and hippocampal attributes. Additionally, this review presents other neuroendocrine mechanisms that may be involved in modulating the relationship among seasonality, gonadal hormone release, and the hippocampus and spatial cognition, including seasonal rhythms of steroid hormone binding globulins, neurosteroids, sex steroid hormone receptor expression, and hormone interactions. Here, endocrinology, ecology, and behavioral neuroscience are brought together to present an overview of the research demonstrating the mechanistic effects of systemic gonadal hormones on spatial cognition and the hippocampus, while, at a functional level, superimposing seasonal effects to examine ecologically-relevant circannual changes in gonadal hormones and spatial behaviors.
•Variation in gonadal hormones can affect the hippocampus and spatial cognition.•This review explores if seasonal hormonal release modulates seasonal changes in the hippocampus and spatial cognition.•This review also considers other endocrinological mechanisms that also may vary seasonally.
The production of new neurons in the brains of adult animals was first identified by Altman and Das in 1965, but it was not until the late 20th century when methods for visualizing new neuron ...production improved that there was a dramatic increase in research on neurogenesis in the adult brain. We now know that adult neurogenesis is a ubiquitous process that occurs across a wide range of taxonomic groups. This process has largely been studied in mammals; however, there are notable differences between mammals and other taxonomic groups in how, why and where new neuron production occurs. This Review will begin by describing the processes of adult neurogenesis in reptiles and identifying the similarities and differences in these processes between reptiles and model rodent species. Further, this Review underscores the importance of appreciating how wild-caught animals vary in neurogenic properties compared with laboratory-reared animals and how this can be used to broaden the functional and evolutionary understanding of why and how new neurons are produced in the adult brain. Studying variation in neural processes across taxonomic groups provides an evolutionary context to adult neurogenesis while also advancing our overall understanding of neurogenesis and brain plasticity.
Individual variation in stable behavioural traits may explain variation in ecologically relevant behaviours such as foraging, dispersal, anti-predator behaviour, and dominance. We investigated ...behavioural variation in mountain chickadees, a North American parid that lives in dominance-structured winter flocks, using two common measures of behavioural profile: exploration of a novel room and novel object exploration. We related those behavioural traits to dominance status in male chickadees following brief, pairwise encounters. Low-exploring birds (birds that visited less than four locations in the novel room) were significantly more likely to become dominant in brief, pairwise encounters with high-exploring birds (i.e. birds that visited all perching locations within a novel room). On the other hand, there was no relationship between novel object exploration and dominance. Interestingly, novel-room exploration was also not correlated with novel object exploration. These results suggest that behavioural profile may predict the social status of group-living individuals. Moreover, our results contradict the idea that novel object exploration and novel-room exploration are always interchangeable measures of individuals' sensitivity to environmental novelty.
Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we ...aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor.
Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator’s choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS).
Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T.
In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.
•Adjuvant platinum-based chemotherapy is accepted as standard of care in stage II and III (NSCLC) patients.•Several studies addressed the question of whether molecular tumor markers may serve as predictive biomarkers.•ITACA was planned to evaluate the predictive utility of ERCC1 and TS mRNA expression levels in completely resected NSCLC.•ITACA results indicate that adjuvant chemotherapy customization based on ERCC1 and TS mRNA levels did not improve efficacy.•In terms of safety, the pharmacogenomic-driven arm was associated with better efficacy/toxicity ratio.
Previous to the 1980’s, the prevailing neuroscience dogma held that no new neurons were produced in the brains of adult mammals. Now, we understand that the production of new neurons, or ...neurogenesis, is a common and plastic process in the adult brain. To date, however, researchers have not come to a unified understanding of the functional significance of neurogenesis. Several factors have been shown to modulate hippocampal neurogenesis including spatial learning, stress, and aspects of environmental change, but questions still remain. How do these modulating factors overlap? Which aspects of environmental change induce a stress response? Is there a relationship between hippocampal neurogenesis, the stress response, and environmental change? Can this relationship be altered when taking into consideration other factors such as perception and predictability of the environment? Finally, do results from neurobiological research on laboratory rodents translate to wild systems? This review attempts to address these questions and synthesize research from the fields of ecology, psychology, and behavioral neuroscience.
Several clinical trials are evaluating gene transfer as a therapeutic approach to treat cardiac diseases. Although it has just started on the path to clinical application, recent advances in gene ...delivery technologies with increasing knowledge of underlying mechanisms raise great expectations for the cardiac gene therapy. Although in vivo experiments using small animals provide the therapeutic potential of gene transfer, there exist many fundamental differences between the small animal and the human hearts. Before applying the therapy to clinical patients, large animal studies are a prerequisite to validate the efficacy in an animal model more relevant to the human heart. Several key factors including vector type, injected dose, delivery method and targeted cardiac disease are all important factors that determine the therapeutic efficacy. Selecting the most optimal combination of these factors is essential for successful gene therapy. In addition to the efficacy, safety profiles need to be addressed as well. In this regard, large animal studies are best suited for comprehensive evaluation at the preclinical stages of therapeutic development to ensure safe and effective gene transfer. As the cardiac gene therapy expands its potential, large animal studies will become more important to bridge the bench side knowledge to the clinical arena.
Stress experienced during ontogeny can have profound effects on the adult phenotype. However, stress can also be experienced intergenerationally, where an offspring's phenotype can be moulded by ...stress experienced by the parents. Although early-life and intergenerational stress can alter anatomy, physiology, and behaviour, nothing is known about how these stress contexts interact to affect the neural phenotype. Here, we examined how early-life and intergenerational stress affect the brain in eastern fence lizards (
Sceloporus undulatus
). Some lizard populations co-occur with predatory fire ants, and stress from fire ant attacks exerts intergenerational physiological and behavioural changes in lizards. However, it is unclear if intergenerational stress, or the interaction between intergenerational and early-life stress, modulates the brain. To test this, we captured gravid females from fire ant invaded and uninvaded populations, and subjected offspring to three early-life stress treatments: (1) fire ant attack, (2) corticosterone, or (3) a control. Corticosterone and fire ant attack decreased some aspects of the neural phenotype while population of origin and the interaction of early-life stress and population had no effects on the brain. These results suggest that early-life stressors may better predict adult brain variation than intergenerational stress in this species.
Intrapericardial drug delivery is a promising procedure, with the ability to localize therapeutics with the heart. Gelfoam particles are nontoxic, inexpensive, nonimmunogenic and biodegradable ...compounds that can be used to deliver therapeutic agents. We developed a new percutaneous approach method for intrapericardial injection, puncturing the pericardial sac safely under fluoroscopy and intravascular ultrasound (IVUS) guidance. In a porcine model of myocardial infarction (MI), we deployed gelfoam particles carrying either (a) autologous mesenchymal stem cells (MSCs) or (b) an adenovirus encoding enhanced green fluorescent protein (eGFP) 48 h post-MI. The presence of MSCs and viral infection at the infarct zone was confirmed by immunoflourescence and PCR. Puncture was performed successfully in 16 animals. Using IVUS, we successfully determined the size of the pericardial space before the puncture, and safely accessed that space in setting of pericardial effusion and also adhesions induced by the MI. Intrapericardial injection of gelfoam was safe and reliable. Presence of the MSCs and eGFP expression from adenovirus in the myocardium were confirmed after delivery. Our novel percutaneous approach to deliver (stem-) cells or adenovirus was safe and efficient in this pre-clinical model. IVUS-guided delivery is a minimally invasive procedure that seems to be a promising new strategy to deliver therapeutic agents locally to the heart.
Spatial abilities have been associated with many ecologically relevant behaviours such as territoriality, mate choice, navigation and acquisition of food resources. Differential demands on spatial ...abilities in birds and mammals affect the hippocampus, the region of the brain responsible for spatial processing. In some bird and mammal species, higher demands on spatial abilities are associated with larger hippocampal volumes. The medial and dorsal cortices are the putative reptilian homologues of the mammalian hippocampus, yet few studies have examined the relationship between these brain areas and differential spatial use strategies in reptiles. Furthermore, many studies in birds and mammals compare hippocampal attributes between species that use space differently, potentially confounding species-specific effects with effects due to differential behaviours in spatial use. Here, we investigated the relationship between spatial use strategies and medial and dorsal cortical volumes in males of the side-blotched lizard. In this species, males occur in three different morphs, each morph using different spatial niches: large territory holders, small territory holders and nonterritory holders with home ranges smaller than the territories of small territory holders. We found that large territory holders had larger dorsal cortical volumes relative to the remainder of the telencephalon compared with nonterritorial males, and that small territory holders were intermediate. These results suggest that some aspect of holding a large territory may place demands on spatial abilities, which is reflected in a brain region thought partially responsible for spatial processing.
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