Medical care in early modern Venice

In early modern Venice, a wide range and large number of people offered care to the sick. This study utilizes Venice’s civic death registers to assess when and why the sick and dying accessed medical care, and how this changed over the course of the early modern period. The detailed registers permit consideration of the profile of medical practitioners, key aspects of patient identity, the involvement of institutions in the provision of medical care, and the relationship between type of illness and the propensity of the sufferer to seek medical support. This study assesses the type, number, density and distribution of practitioners in the city. Recourse to medical care was affected by age, social status and type of illness. A web of institutions increased levels of medical engagement amongst those of lower social status. Recourse to medical care by adults increased to a high level during the seventeenth century, and became near-universal by the end of the eighteenth century

Health passes, print and public health in early modern Europe

Early modern governments produced a wide range of printed texts as part of their public health strategies, including broadsheets, flysheets and pamphlets. This study focuses on health passes, a form of ephemeral print which asserted that the bearer had travelled from a city which was free from plague. Passes were printed forms with textual, iconographic and material features which sought to enhance their authority, credibility and usability. Completed forms provide evidence of their users and of how passes were adapted in response to particular perceived threats. This study examines passes issued by a large number of European cities to argue for the development of a shared European culture of public health print, inspired by recognition of print’s persuasiveness, efficiency and capacity to transcend the boundaries of place

Cadherins: Actin with the Cytoskeleton to Form Synapses

Classic cadherins are calcium-dependent homophilic cell adhesion molecules that are enriched at synapses and thought to function in target recognition and adhesion at synaptic junctions. This brief review highlights evidence that cadherins and their associated catenins play a role in directing the development of pre- and postsynaptic specializations. In particular, the question of whether cadherin regulation of the actin cytoskeleton at discrete contact sites translates into the assembly of synaptic compartments will be explored

Effects of glyceollin on mRNA expression in the female mouse brain.

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Glys exhibit mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Glys on brain physiology and function are unknown. The purpose of the experiments summarized in this dissertation was to gain an understanding of the effects of Gly on brain-related functions in the female mouse brain through the observation of changes in gene expression. For our initial studies, we treated ovariectomized Swiss Webster (CFW) mice with 17-β estradiol (E2) or placebo pellets, followed by 11 days of exposure to Glys or vehicle i.p. injections. We then performed microarray (Chapter 2) and RNA-sequencing analyses (Chapter 3) on total RNA extracted from whole brain hemispheres and identified differentially expressed genes (DEGs) between our treatment groups. Our results suggested that Glys, when in combination with E2 (E2+Gly), can oppose the E2 effects on gene expression and vice versa, can regulate genes similarly to E2, and can also have E2-independent effects on gene expression in the female brain. However, the whole brain experiments did not take into account the heterogeneity of the brain. Different brain regions perform unique and distinct functions and can differ markedly in terms of gene expression, so we wanted to determine if Glys had any brain region-specific effects on gene expression. Additionally, as the whole brain studies only included a single time point of exposure to Glys, we evaluated the effects of a single acute dose of Glys (2, 24 and 48 hr) as well as chronic exposure to Glys (multiple doses of Glys for 7 consecutive days) on gene expression in distinct brain regions. Therefore, in Chapter 4, we evaluated the effects of acute vs. chronic doses of Glys alone and in combination with E2 on gene expression in the hypothalamus, hippocampus, and cortex of the female mouse brain. Our results suggest that Glys can rapidly upregulate the expression of genes like growth hormone (Gh) in the hypothalamus, hippocampus and cortex and prolactin (Prl) in the hypothalamus and cortex, 2h or 24h after administration of a single acute dose. Thus Glys may potentially affect neuronal processes like food intake, stress and cognition through its effects on Gh and Prl gene expression in the female mouse brain. As all of the above chapters involve a peripheral administration of Glys (intraperitoneal injections), it was unclear if Glys affect gene expression through direct action at the neuron or through some indirect peripheral effect. To address this issue, in Chapter 5 we screened five immortalized neural cell lines derived from the adult female mouse hypothalamus (mHypoA-50, 51, 55, 59 and 63) for the presence of our genes of interest and E2 responsiveness. Based on consistency of mRNA transcript detection and E2 responsivity, we selected two cell lines (mHypoA-55 and 63) that may be suitable for future experiments to determine the direct effect of Glys on gene expression at the neuron. Together this work provides novel information on the effects of Glys in the brain, which is important in order to develop its use as a dietary supplement and/or therapeutic agent

BDNF mobilizes synaptic vesicles and enhances synapse formation by disrupting cadherin–β-catenin interactions

Neurons of the vertebrate central nervous system have the capacity to modify synapse number, morphology, and efficacy in response to activity. Some of these functions can be attributed to activity-induced synthesis and secretion of the neurotrophin brain-derived neurotrophic factor (BDNF); however, the molecular mechanisms by which BDNF mediates these events are still not well understood. Using time-lapse confocal analysis, we show that BDNF mobilizes synaptic vesicles at existing synapses, resulting in small clusters of synaptic vesicles “splitting” away from synaptic sites. We demonstrate that BDNF's ability to mobilize synaptic vesicle clusters depends on the dissociation of cadherin–β-catenin adhesion complexes that occurs after tyrosine phosphorylation of β-catenin. Artificially maintaining cadherin–β-catenin complexes in the presence of BDNF abolishes the BDNF-mediated enhancement of synaptic vesicle mobility, as well as the longer-term BDNF-mediated increase in synapse number. Together, this data demonstrates that the disruption of cadherin–β-catenin complexes is an important molecular event through which BDNF increases synapse density in cultured hippocampal neurons

Synaptic Innervation Density Is Regulated by Neuron-Derived BDNF

AbstractIn this report, we have examined the role of neuron-derived BDNF at an accessible synapse, that of preganglionic neurons onto their sympathetic neuron targets. Developing and mature sympathetic neurons synthesize BDNF, and preganglionic neurons express the full-length BDNF/TrkB receptor. When sympathetic neuron-derived BDNF is increased 2- to 4-fold in transgenic mice, preganglionic cell bodies and axons hypertrophy, and the synaptic innervation to sympathetic neurons is increased. Conversely, when BDNF synthesis is eliminated in BDNF −/− mice, preganglionic synaptic innervation to sympathetic neurons is decreased. Together these results indicate that variations in neuronal neurotrophin synthesis directly regulate neuronal circuitry by selectively modulating synaptic innervation density