Marina Silveira

Alzheimer‐associated Aβ oligomers impact the central nervous system to induce peripheral metabolic deregulation

Alzheimers disease (AD) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in AD patients. Here, we show that intracerebroventricular infusion of AD‐associated Aβ oligomers (AβOs) in mice triggered peripheral glucose intolerance, a phenomenon further verified in two transgenic mouse models of AD. Systemically injected AβOs failed to induce glucose intolerance, suggesting AβOs target brain regions involved in peripheral metabolic control. Accordingly, we show that AβOs affected hypothalamic neurons in culture, inducing eukaryotic translation initiation factor 2α phosphorylation (eIF2α‐P). AβOs further induced eIF2α‐P and activated pro‐inflammatory IKKβ/NF‐κB signaling in the hypothalamus of mice and macaques. AβOs failed to trigger peripheral glucose intolerance in tumor necrosis factor‐α (TNF‐α) receptor 1 knockout mice. Pharmacological inhibition of brain inflammation and endoplasmic reticulum stress prevented glucose intolerance in mice, indicating that AβOs act via a central route to affect peripheral glucose homeostasis. While the hypothalamus has been largely ignored in the AD field, our findings indicate that AβOs affect this brain region and reveal novel shared molecular mechanisms between hypothalamic dysfunction in metabolic disorders and AD.

Studies on molluscan shells: Contributions from microscopic and analytical methods

Molluscan shells have always attracted the interest of researchers, from biologists to physicists, from paleontologists to materials scientists. Much information is available at present, on the elaborate architecture of the shell, regarding the various Mollusc classes. The crystallographic characterization of the different shell layers, as well as their physical and chemical properties have been the subject of several investigations. In addition, many researches have addressed the characterization of the biological component of the shell and the role it plays in the hard exoskeleton assembly, that is, the biomineralization process. All these topics have seen great advances in the last two or three decades, expanding our knowledge on the shell properties, in terms of structure, functions and composition. This involved the use of a range of specialized and modern techniques, integrating microscopic methods with biochemistry, molecular biology procedures and spectroscopy. However, the factors governing synthesis of a specific crystalline carbonate phase in any particular layer of the shell and the interplay between organic and inorganic components during the biomineral assembly are still not widely known. This present survey deals with microstructural aspects of molluscan shells, as disclosed through use of scanning electron microscopy and related analytical methods (microanalysis, X-ray diffraction, electron diffraction and infrared spectroscopy). These already published data provide relevant information on shells and also contribute for better understanding the biomineralization process.

Ultrastructural studies on a "nine plus one" flagellum 1.

The application of several preparative procedures to the study of the 9 + 1 flagellum has allowed to visualize many structural details not yet observed on similar organelles. A three-dimensional model is proposed for its unique central cylinder, which consists of three distinct zones: a dense axial zone, surrounded by an intermediate one and a cortical sheath. This latter is formed by two regularly spaced, equal helices that constitute the wall of the cylinder and to which the radial spokes are attached. Although a radial ninefold symmetry is apparent in cross sections of these flagella, the presence of the two helices precludes such symmetry from being extended to its central unit.

Electron microscopic observations of human hair medulla

In the study of human hair, medulla is the less studied structure because it is believed that it has no influence on the fibre properties. The aim of this paper is to contribute to the better understanding of medulla morphology. Using reproducible methods for hair samples preparations allowed observing the inner fibre by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Three medulla subunits were observed in cryofractured samples. In addition, the application of plasma etching on samples allowed accessing chemical differences between them. Two kinds of medulla were identified using stereomicroscopy: thin and thick medulla. They were morphologically differentiated using TEM. These methods can be used to study systematically the effects of medulla on hair properties and to evaluate the efficiency of cosmetic products.

Fine structural observations on the protonephridium of the terrestrial triclad Geoplana pasipha

SummaryThe protonephridial system of the terrestrial triclad Geoplana pasipha was studied by electron microscopy. In general construction it conforms to that of the freshwater planarian Dugesia tigrina (McKanna, 1968, 1968 a).Ultrastructural details permit the identification of proximal, collecting, osmoregulatory and nephridiopore regions. Intralumenal material is frequently observed within the tubules, whose cells are always joined by septate junctions. Cilia are numerous and possibly contribute to the flow of water and solutes along the system. Proximal tubules have a peculiar, particulate membrane coat, while a continuous coat, densely stainable with ruthenium red lines the more distal, unciliated tubules.

Intraaxonemal glycogen in "9+1" flagella of flatworms.

The paired, free, 9+1 sperm tails of three species of land planarians have been studied by means of ultrathin sections. They are identical to other 9+1 axonemes already described for several flatworm species, except that they contain an orderly arrangement of dense granules. These granules are especially prominent in one species, Geoplana pasipha. On the basis of their being selectively stained for glycogen by the PA—TSC—SP technique of Thiery, these granules were identified in the present study as beta-glycogen particles. The significance of such glycogen deposits within the flagellar apparatus of triclads still remains to be ascertained.

Fatness rather than leptin sensitivity determines the timing of puberty in female mice

Leptin is a permissive factor for the onset of puberty. However, changes in adiposity frequently influence leptin sensitivity. Thus, the objective of the present study was to investigate how changes in body weight, fatness, leptin levels and leptin sensitivity interact to control the timing of puberty in female mice. Pre-pubertal obesity, induced by raising C57BL/6 mice in small litters, led to an early puberty onset. Inactivation of Socs3 gene in the brain or exclusively in leptin receptor-expressing cells reduced the body weight and leptin levels at pubertal onset, and increased leptin sensitivity. Notably, these female mice exhibited significant delays in vaginal opening, first estrus and onset of estrus cyclicity. In conclusion, our findings suggest that increased leptin sensitivity did not play an important role in favoring pubertal onset in female mice. Rather, changes in pubertal body weight, fatness and/or leptin levels were more important in influencing the timing of puberty.

Neuronal STAT5 signaling is required for maintaining lactation but not for postpartum maternal behaviors in mice

Prolactin and placental lactogens control mammary development and lactation as well as play an important role in maternal behaviors. However, the molecular mechanisms in the brain responsible for this regulation remain largely unknown. Therefore, the present study investigated whether Signal Transducer and Activator of Transcription 5 (STAT5) signaling in the brain, the key transcriptional factor recruited by prolactin receptor and other hormones, is required for postpartum maternal behavior, maintenance of lactation and offspring growth. Neuronal ablation of STAT5 impaired the control of prolactin secretion and reduced the hypothalamic expression of suppressors of cytokine signaling (i.e., SOCS3 and CISH). In addition, neuronal STAT5 deletion attenuated the hyperphagia commonly observed during lactation by decreasing the hypothalamic expression of orexigenic neurotransmitters such as the neuropeptide Y and agouti-related protein. The lower food intake of lactating neuron-specific STAT5 knockout females resulted in reduced milk production and offspring growth. Unexpectedly, postpartum maternal behavior expression was not impaired in neuron-specific STAT5 knockout females. On the contrary, the latency to retrieve and group the pups into the nest was reduced in mutant dams. Finally, we demonstrated that approximately 30% of recorded neurons in the medial preoptic area were acutely depolarized by prolactin suggesting that fast STAT5-independent signaling pathways may be involved in the regulation of maternal behaviors. Overall, our results revealed important information about the molecular mechanisms recruited by hormones to orchestrate the activation of neural circuitries engaged in the induction of maternal care.

Symbiosis between a pelagic flatworm and a dinoflagellate from a tropical area: structural observations

A morphological account on the endosymbiosis between Amphiscolops sp and Amphidinium sp is given, based on scanning and transmission electron microscopy observations. The algal symbionts (15–20 µm in diameter) are found among cells of the peripheral parenchyma. Amphidinium sp. has a single pyrenoid of the multiple-stalked type, with several chloroplast lobes radiating from it. A comparison with A. klebsii is made. Our observations reinforce the assumption of selectivity of Amphiscolops for the symbiotic genus Amphidinium.

GnRH neuron activity and pituitary response in estradiol-induced vs proestrous luteinizing hormone surges in female mice

During the female reproductive cycle, estradiol exerts negative and positive feedback at both the central level to alter gonadotropin-releasing hormone (GnRH) release and at the pituitary to affect response to GnRH. Many studies of the neurobiologic mechanisms underlying estradiol feedback have been done on ovariectomized, estradiol-replaced (OVX+E) mice. In this model, GnRH neuron activity depends on estradiol and time of day, increasing in estradiol-treated mice in the late afternoon, coincident with a daily luteinizing hormone (LH) surge. Amplitude of this surge appears lower than in proestrous mice, perhaps because other ovarian factors are not replaced. We hypothesized GnRH neuron activity is greater during the proestrous-preovulatory surge than the estradiol-induced surge. GnRH neuron activity was monitored by extracellular recordings from fluorescently tagged GnRH neurons in brain slices in the late afternoon from diestrous, proestrous, and OVX+E mice. Mean GnRH neuron firing rate was low on diestrus; firing rate was similarly increased in proestrous and OVX+E mice. Bursts of action potentials have been associated with hormone release in neuroendocrine systems. Examination of the patterning of action potentials revealed a shift toward longer burst duration in proestrous mice, whereas intervals between spikes were shorter in OVX+E mice. LH response to an early afternoon injection of GnRH was greater in proestrous than diestrous or OVX+E mice. These observations suggest the lower LH surge amplitude observed in the OVX+E model is likely not attributable to altered mean GnRH neuron activity, but because of reduced pituitary sensitivity, subtle shifts in action potential pattern, and/or excitation-secretion coupling in GnRH neurons.