scholarly journals Hormetic effect of amyloid-beta peptide in hippocampal synaptic plasticity and memory

2021 ◽  
Vol 11 (40) ◽  
pp. 156-156
Author(s):  
Daniela Puzzo ◽  
Agostino Palmeri
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Beta ◽  
Hippocampal Slices ◽  
Reference Memory ◽  
High Dose ◽  
Low Doses ◽  
Hormetic Effect ◽  
Physiologic Function ◽  
High Doses

Background: The term hormesis refers to a biphasic dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition represented by a J-shaped or U-shaped curve, depending on the parameter measured (Calabrese and Baldwin, Hum Exp Toxicol, 2002). Indeed, several, if not all, physiological molecules (i.e. glutamate, glucocorticoids, nitric oxide) are likely to present a hormetic effect, exhibiting opposite effects at high or low concentrations. In the last few years, we have focused on amyloid-beta (A), a peptide widely known because it is produced in high amounts during Alzheimer’s disease (AD). A is considered a toxic fragment causing synaptic dysfunction and memory impairment (Selkoe, Science, 2002). However, the peptide is normally produced in the healthy brain and growing evidences indicate that it might have a physiologic function. Aim: Based on previous results showing that picomolar concentrations of A42 enhance synaptic plasticity and memory (Puzzo et al, J Neurosci, 2008) and that endogenous A is necessary for synaptic plasticity and memory (Puzzo et al, Ann Neurol, 2011), the aim of our study was to demonstrate the hormetic role of A in synaptic plasticity and memory. Methods: We used 3-month old wild type mice to analyze how synaptic plasticity, measured on hippocampal slices in vitro, and spatial reference memory were modified by treatment with different doses of A (from 2 pM to 20 μM). Results: We demonstrated that A has a hormetic effect (Puzzo et al, Neurobiol Aging, 2012) with low-doses (200 pM) stimulating synaptic plasticity and memory and high-doses (≥ 200 nM) inhibiting these processes. Conclusions: Our results suggest that, paradoxically, very low doses of A might serve to enhance memory at appropriate concentrations and conditions. These findings raise several issues when designing effective and safe approaches to AD therapy.

scholarly journals Anti-Inflammatory Properties of Low and High Doxycycline Doses: AnIn VitroStudy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Roberta Di Caprio ◽  
Serena Lembo ◽  
Luisa Di Costanzo ◽  
Anna Balato ◽  
Giuseppe Monfrecola
Keyword(s):  
Gene Expression ◽  
Skin Diseases ◽  
High Dose ◽  
Low Doses ◽  
Dose Administration ◽  
Doxycycline Treatment ◽  
Anti Inflammatory ◽  
High Doses ◽  
Bacterial Resistances

Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, ourin vitrostudy suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.

scholarly journals Toll-Like Receptor Signaling in Airborne Burkholderia thailandensis Infection

2009 ◽  
Vol 77 (12) ◽  
pp. 5612-5622 ◽  
Author(s):  
T. Eoin West ◽  
Thomas R. Hawn ◽  
Shawn J. Skerrett
Keyword(s):  
Low Dose ◽  
Inflammatory Responses ◽  
High Dose ◽  
Tlr Signaling ◽  
Necrosis Factor Alpha ◽  
Airborne Infection ◽  
Essential Components ◽  
High Doses

ABSTRACT Melioidosis is a tropical disease endemic in southeast Asia and northern Australia caused by the gram-negative soil saprophyte Burkholderia pseudomallei. Although infection is often systemic, the lung is frequently involved. B. thailandensis is a closely related organism that at high doses causes lethal pneumonia in mice. We examined the role of Toll-like receptors (TLRs), essential components of innate immunity, in vitro and in vivo during murine B. thailandensis pneumonia. TLR2, TLR4, and TLR5 mediate NF-κB activation by B. thailandensis in transfected HEK293 or CHO cells. In macrophages, TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are required for tumor necrosis factor alpha production induced by B. thailandensis. In low-dose airborne infection, TLR4 is needed for early, but not late, bacterial containment, and MyD88 is essential for control of infection and host survival. TLR2 and TLR5 are not necessary to contain low-dose infection. In high-dose airborne infection, TLR2 deficiency confers a slight survival advantage. Lung and systemic inflammatory responses are induced by low-dose inhaled B. thailandensis independently of individual TLRs or MyD88. These findings suggest that redundancy in TLR signaling or other MyD88-dependent pathways may be important in pneumonic B. thailandensis infection but that MyD88-independent mechanisms of inflammation are also activated. TLR signaling in B. thailandensis infection is substantially comparable to signaling induced by virulent B. pseudomallei. These studies provide additional insights into the host-pathogen interaction in pneumonic Burkholderia infection.

scholarly journals Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans

2000 ◽  
Vol 44 (11) ◽  
pp. 2932-2938 ◽  
Author(s):  
O. Marchetti ◽  
J. M. Entenza ◽  
D. Sanglard ◽  
J. Bille ◽  
M. P. Glauser ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Cyclosporine A ◽  
Test Organism ◽  
The Other ◽  
High Dose ◽  
Therapeutic Results ◽  
Fluconazole Therapy ◽  
High Doses

ABSTRACT Recent observations demonstrated that fluconazole plus cyclosporine (Cy) synergistically killed Candida albicans in vitro. This combination was tested in rats with C. albicansexperimental endocarditis. The MICs of fluconazole and Cy for the test organism were 0.25 and >10 mg/liter, respectively. Rats were treated for 5 days with either Cy, amphotericin B, fluconazole, or fluconazole-Cy. Although used at high doses, the peak concentrations of fluconazole in the serum of rats (up to 4.5 mg/liter) were compatible with high-dose fluconazole therapy in humans. On the other hand, Cy concentrations in serum (up to 4.5 mg/liter) were greater than recommended therapeutic levels. Untreated rats demonstrated massive pseudohyphal growth in both the vegetations and the kidneys. However, only the kidneys displayed concomitant polymorphonuclear infiltration. The therapeutic results reflected this dissociation. In the vegetations, only the fungicidal fluconazole-Cy combination significantly decreased fungal densities compared to all groups, including amphotericin B (P < 0.0001). In the kidneys, all regimens except the Cy regimen were effective, but fluconazole-Cy remained superior to amphotericin B and fluconazole alone in sterilizing the organs (P < 0.0001). While the mechanism responsible for the fluconazole-Cy interaction is hypothetical, this observation opens new perspectives for fungicidal combinations between azoles and other drugs.

scholarly journals Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection.

1987 ◽  
Vol 166 (6) ◽  
pp. 1716-1733 ◽  
Author(s):  
J S Weber ◽  
G Jay ◽  
K Tanaka ◽  
S A Rosenberg
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Interleukin 2 ◽  
Class I ◽  
High Dose ◽  
Class I Mhc ◽  
High Doses ◽  
I Gene

We have shown that two weakly immunogenic MCA sarcomas developed in our laboratory that are sensitive to high-dose IL-2 immunotherapy express class I MHC in vivo and in vitro. Two nonimmunogenic MCA sarcomas are relatively insensitive to IL-2 therapy and express minimal or no class I MHC molecules in vivo and in vitro. To study the role of MHC in the therapy of tumors with IL-2, a class I-deficient murine melanoma, B16BL6, was transfected with the Kb class I gene. Expression of class I MHC rendered B16BL6 advanced pulmonary macrometastases sensitive to IL-2 immunotherapy. 3-d micrometastases of CL8-2, a class I transfected clone of B16BL6, were significantly more sensitive to IL-2 therapy than a control nontransfected line. Expression of Iak, a class II MHC molecule, had no effect on IL-2 therapy of transfectant pulmonary micrometastases in F1 mice. By using lymphocyte subset depletion with mAbs directed against Lyt-2, therapy of class I transfectant macrometastases with high-dose IL-2 was shown to involve an Lyt-2 cell. In contrast, regression of micrometastases treated with low-dose IL-2 involved Lyt-2+ cells, but regression mediated by high doses of IL-2 did not. We hypothesize that both LAK and Lyt-2+ T cells effect IL-2-mediated elimination of micrometastases, but only Lyt-2+ T cells are involved in macrometastatic regression. Low doses of IL-2 stimulate Lyt-2+ cells to eliminate class I-expressing micrometastases, but high doses of IL-2 can recruit LAK cells to mediate regression of micrometastases independent of class I expression. Only high-dose IL-2, mediating its effect predominantly via Lyt-2+ cells, is capable of impacting on MHC class I-expressing macrometastases. Macrometastases devoid of class I MHC antigens appear to be resistant to IL-2 therapy.

scholarly journals P1-014: Hormetic effect of amyloid-beta peptide on synaptic plasticity and memory

2011 ◽  
Vol 7 ◽  
pp. S116-S116
Author(s):  
Daniela Puzzo ◽  
Ottavio Arancio ◽  
Lucia Privitera ◽  
Agostino Palmeri ◽  
Dario Furnari
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Beta ◽  
Amyloid Beta Peptide ◽  
Hormetic Effect ◽  
Beta Peptide

scholarly journals Protective Bystander Effects Simulated with the State-Vector Model

Dose-Response ◽  
2007 ◽  
Vol 5 (3) ◽  
pp. dose-response.0 ◽  
Author(s):  
Helmut Schöllnberger ◽  
Peter M. Eckl
Keyword(s):  
State Vector ◽  
Hybrid Cell ◽  
The State ◽  
Vector Model ◽  
High Dose ◽  
Data Sets ◽  
Low Doses ◽  
Protective Effects ◽  
Multistage Model

Apoptosis induced in non-hit bystander cells is an important biological mechanism which operates after exposure to low doses of low-LET radiation. This process was implemented into a deterministic multistage model for in vitro neoplastic transformation: the State-Vector Model (SVM). The new model is tested on two data sets that show a reduction of the transformation frequency below the spontaneous level after exposure of the human hybrid cell line CGL1 to low doses of γ-radiation. Stronger protective effects are visible in the data for delayed plating while the data for immediate plating show more of an LNT-like dose-response curve. It is shown that the model can describe both data sets. The calculation of the time-dependent numerical solution of the model also allows to obtain information about the time-dependence of the protective apoptosis-mediated process after low dose exposures. These findings are compared with experimental observations after high dose exposures.

scholarly journals Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Daniel Santos ◽  
Francisco Gonzalez-Perez ◽  
Xavier Navarro ◽  
Jaume del Valle
Keyword(s):  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Collagen Matrix ◽  
High Dose ◽  
Organotypic Cultures ◽  
High Doses ◽  
Dose Dependent

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo.

scholarly journals Low-DoseAronia melanocarpaConcentrate Attenuates Paraquat-Induced Neurotoxicity

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
A. J. Case ◽  
D. Agraz ◽  
I. M. Ahmad ◽  
M. C. Zimmerman
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Reactive Oxygen ◽  
High Dose ◽  
Low Doses ◽  
Oxygen Species ◽  
High Doses

Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson’s disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-richAronia melanocarpa(aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity.

scholarly journals High-Dose Intravenous Ribavirin Therapy for Subacute Sclerosing Panencephalitis

2001 ◽  
Vol 45 (3) ◽  
pp. 943-945 ◽  
Author(s):  
Mitsuaki Hosoya ◽  
Shiro Shigeta ◽  
Shuichi Mori ◽  
Akemi Tomoda ◽  
Seiji Shiraishi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Virus Replication ◽  
Subacute Sclerosing Panencephalitis ◽  
Alpha Interferon ◽  
High Dose ◽  
Sspe Virus ◽  
High Doses

ABSTRACT Two patients with subacute sclerosing panencephalitis (SSPE) were treated safely and effectively with high doses of intravenous ribavirin combined with intraventricular alpha interferon. The ribavirin concentrations maintained in the serum and cerebrospinal fluid were higher than those which inhibit SSPE virus replication in vitro and in vivo.

EFFECTS OF X-RADIATION AND OF METABOLIC INHIBITORS ON RAT THYMOCYTES IN VITRO

1962 ◽  
Vol 40 (11) ◽  
pp. 1535-1552 ◽  
Author(s):  
D. K. Myers ◽  
Donna E. DeWolfe ◽  
Kimiko Araki
Keyword(s):  
Oxygen Consumption ◽  
Normal Cell ◽  
Cell Metabolism ◽  
Metabolic Inhibitors ◽  
Low Doses ◽  
Ph Values ◽  
Atp Levels ◽  
Different Temperatures ◽  
High Doses

The survival of X-irradiated thymocytes in vitro was studied after incubation for various periods of time and at different pH values as well as at different temperatures. Death at 25 °C following exposure to high doses of X-radiation may be due to the liberation of destructive enzymes. The effects of high doses could be largely prevented by addition of nicotinamide after irradiation.The cause of cell death at 37 °C following exposure to low doses of X-radiation is still uncertain. Some metabolic inhibitors also showed a considerable difference in their toxicity to thymocytes at 37 °C and at 25 °C. Dinitrophenol, for example, was highly toxic at 37 °C but almost ineffective in killing cells at 25 °C, even though it produced similar decreases in ATP levels at both temperatures. The marked difference in survival of irradiated thymocytes at 37 °C and at 25 °C could therefore be explained if low doses of X-radiation interfered with the normal cell metabolism. However, low doses of radiation, unlike dinitrophenol, did not produce any immediate decrease either in ATP levels or in oxygen consumption of thymocyte suspensions.

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