scholarly journals Nicotine Neurotoxicity Involves Low Wnt1 Signaling in Spinal Locomotor Networks of the Postnatal Rodent Spinal Cord

2021 ◽  
Vol 22 (17) ◽  
pp. 9572
Author(s):  
Jaspreet Kaur ◽  
Graciela L. Mazzone ◽  
Jorge B. Aquino ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Wnt Signaling ◽  
Wistar Rat ◽  
High Dose ◽  
Spinal Neurons ◽  
Double Transgenic Mouse ◽  
Enhanced Expression ◽  
Dorsal Area

The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1 µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5–10 µM) on locomotor networks in-vitro. Nicotine 10 µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5–1 µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes indicating a stress response. Excitotoxicity induced by kainate was contrasted by nicotine (10 µM) in the dorsal area and persisted in central and ventral regions with no change in basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine.

scholarly journals Nicotine Neurotoxicity Involves Low Wnt1 Signaling in Spinal Locomotor Networks of the Postnatal Rodent Spinal Cord

2021 ◽  
Author(s):  
Jaspreet Kaur ◽  
Graciela L. Mazzone ◽  
Jorge B. Aquino ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Wnt Signaling ◽  
Wistar Rat ◽  
High Dose ◽  
Spinal Neurons ◽  
Double Transgenic Mouse ◽  
Enhanced Expression ◽  
Dorsal Area ◽  
Response To Stress

The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5-10µM) on locomotor networks in-vitro. Nicotine 10µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5-1µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes suggesting their response to stress. Excitotoxicity induced by kainate was contrasted by nicotine (10µM) in the dorsal area and persisted in central and ventral regions with no change basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine.

scholarly journals Changes in gap junction expression and function following ischemic injury of spinal cord white matter

2014 ◽  
Vol 112 (9) ◽  
pp. 2067-2075 ◽  
Author(s):  
Karina Goncharenko ◽  
Eftekhar Eftekharpour ◽  
Alexander A. Velumian ◽  
Peter L. Carlen ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Gap Junctions ◽  
Gap Junction ◽  
Glucose Deprivation ◽  
Wistar Rat ◽  
Conduction Loss ◽  
Axonal Dysfunction

Gap junctions are widely present in spinal cord white matter; however, their role in modulating the dynamics of axonal dysfunction remains largely unexplored. We hypothesized that inhibition of gap junctions reduces the loss of axonal function during oxygen and glucose deprivation (OGD). The functional role of gap junctions was assessed by electrophysiological recordings of compound action potentials (CAPs) in Wistar rat spinal cord slices with the sucrose gap technique. The in vitro slices were subjected to 30-min OGD. Gap junction connexin (Cx) mRNA expression was determined by qPCR and normalized to β-actin. A 30-min OGD resulted in reduction of CAPs to 14.8 ± 4.6% of their pre-OGD amplitude ( n = 5). In the presence of gap junction blockers carbenoxolone (Cbx; 100 μM) and 1-octanol (Oct; 300 μM), the CAP reduction in OGD was to only 35.7 ± 5.7% of pre-OGD amplitude in Cbx ( n = 9) and to 37.4 ± 8.9% of pre-OGD amplitude in Oct ( n = 10). Both drugs also noticeably prolonged the half-decline time of CAP amplitudes in OGD from 6.0 min in no-drug conditions to 9.6 min in the presence of Cbx and to 7.7 min in the presence of Oct, suggesting that blocking gap junctions reduces conduction loss during OGD. With application of Cbx and Oct in the setting of OGD, expression of Cx30 and Cx43 mRNA was downregulated. Our data provide new insights into the role of gap junctions in white matter ischemia and reveal the necessity of a cautious approach in determining detrimental or beneficial effects of gap junction blockade in white matter ischemia.

scholarly journals Dose dependence of efficacy but not of safety in sublingual immunotherapy

2016 ◽  
Vol 65 (1) ◽  
Author(s):  
F. Frati ◽  
C. Incorvaia ◽  
F. Marcucci ◽  
L. Sensi ◽  
G. Di Cara ◽  
...  
Keyword(s):  
Sublingual Immunotherapy ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Dose Dependence ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Systemic Reactions ◽  
Significant Difference

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

scholarly journals ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maria Pujantell ◽  
Roger Badia ◽  
Iván Galván-Femenía ◽  
Edurne Garcia-Vidal ◽  
Rafael de Cid ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Immune Activation ◽  
Hpv Infection ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Activation ◽  
Enhanced Expression

AbstractInfection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1–24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.

scholarly journals Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
L. Dalle Carbonare ◽  
M. Mottes ◽  
S. Cheri ◽  
M. Deiana ◽  
F. Zamboni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Physical Exercise ◽  
Cellular Functions ◽  
Enhanced Expression ◽  
Chondrocytic Differentiation ◽  
Marathon Performance ◽  
Array Analyses

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners’ sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions.

scholarly journals Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids, with Cranial and Caudal Extension

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmood Mubasher ◽  
Aseel Sukik ◽  
Ahmed Hassan El Beltagi ◽  
Ali Rahil
Keyword(s):  
Spinal Cord ◽  
Lower Limbs ◽  
High Dose ◽  
Oral Corticosteroids ◽  
Dose Oral ◽  
Multiple Levels ◽  
Romberg Test ◽  
Brain And Spinal Cord ◽  
The Brain

A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis

2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Growth And Survival ◽  
Enhanced Expression ◽  
Stress Environment ◽  
In Vitro Stress ◽  
Carboxyl Esterase

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

scholarly journals Radiotherapy Planning and Molecular Imaging in Lung Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 204-217
Author(s):  
Angelina Filice ◽  
Massimiliano Casali ◽  
Patrizia Ciammella ◽  
Marco Galaverni ◽  
Federica Fioroni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Case Reports ◽  
Locally Advanced ◽  
Inflammatory Cells ◽  
High Rate ◽  
Radiotherapy Planning ◽  
High Dose ◽  
18F Fdg

Introduction: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. Materials and Methods: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually “in vitro” studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. Results: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. : Conclusion: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

Sign in / Sign up

Export Citation Format

Share Document