Biology subjects

Fernandez-Martos, C. M.

Publications and source records attributed to Fernandez-Martos, C. M..

3 recordsLinked to original sources

bioRxiv2021

Alterations in leptin signaling in Amyotrophic Lateral Sclerosis (ALS)

Leptin has been suggested to play a role in amyotrophic lateral sclerosis (ALS), a fatal progressive and neurodegenerative disease. This adipokine has previously been shown to be associated with a lower risk of ALS disease and to confer a survival advantage in ALS patients. However, the role of leptin in the progression of ALS is unknown. Indeed, our understanding of the mechanisms underlying leptins effects in the pathogenesis of ALS is very limited, and it is fundamental to determine whether alterations in leptins actions take place in this neurodegenerative disease. To characterize the association between leptin signaling and the clinical course of ALS we assessed the mRNA and protein expression profiles of leptin, the long leptin receptor (Ob-Rb) and leptin-related signaling pathways over the time course of the disease (onset and end-stage of disease), in TDP-43A315T mice compared to age-matched WT littermates. In addition, at the selected time-points immunoassay analysis was conducted to characterize plasma levels of total ghrelin, the adipokines (resistin and leptin) and metabolic proteins (plasminogen activator inhibitor type 1 (PAI-1), gastric inhibitory peptide (GIP), glucagon like peptide 1 (GLP-1), insulin and glucagon) in TDP-43A315T mice compared to WT controls. Our results indicate alterations in leptin signaling in the spinal cord and the hypothalamus on the backdrop of TDP-43-induced deficits in mice, providing new evidence about the pathways that could link leptin signaling to ALS.

neuroscience↗

bioRxiv2021

Effect of ozone exposure on Amyotrophic Lateral Sclerosis (ALS) pathology using a mice model of TDP-43 proteinopathy

BackgroundOzone (O3), one of the main photochemical pollutants in the atmosphere today, is a serious health risk factor. Although the effects of O3 exposure have been documented on many diseases, they have not yet been examined on Amyotrophic Lateral Sclerosis (ALS)- a fatal progressive and neurodegenerative disease. ObjectivesTo investigate the effect of the O3 exposure in a mice model of TDP-43 proteinopathy, exploring a possible association between the O3 exposure and the ALS pathogenesis. MethodsTDP-43A315T and wild-type (WT) mice were exposed to O3 (0.25 ppm) or filtered air (FA) for 15 days (4 hours/day). We assessed (1) weight loss (2) motor performance (3) plasma glucose content and (4) metabolic markers from plasma samples of the animals. ResultsThroughout the experiment, we observed a progressive decline in body weight and the motor coordination in TDP-43A315T mice compared to WT controls. Although there was a trend, there were no significant differences in the decline of body weight of TDP-43A315T mice when exposed to either FA or O3. In O3-TDP-43A315T mice, the disease duration lasted longer. In addition, O3-TDP-43A315T mice showed improvements in motor performance as well TDP-43A315T mice were hypoglycemic compared to WT mice. However, FA-TDP-43A315T mice showed lower plasma glucose levels at the disease end-stage. We found altered levels of adipokines and metabolic proteins in TDP-43A315T mice compared to WT controls. A positive correlation was found among GIP and glucagon compared to insulin concentrations in control mice. Interestingly, resistin, Gastric Inhibitory Peptide (GIP), Glucagon Like Peptide 1 (GIP-1) and insulin levels were higher in O3-TDP-43A315T mice. DiscussionWe provide new evidence about a mechanistic link between O3 exposure and the improvement of the metabolic disturbances present in TDP-43A315T mice. Further studies are needed to corroborate the obtained results as they warrant to understanding the underlying mechanisms.

neuroscience↗

bioRxiv2020

Enhanced anti-amyloid effect of combined leptin and pioglitazone in APP/PS1 transgenic mice

BackgroundAlzheimers disease (AD) has challenged single-target therapeutic strategies, raising the possibility that combined therapies may offer a more effective treatment strategy. ObjectiveThere is substantial evidence for the efficacy of leptin (L) (neuroprotective hormone) and pioglitazone (P) (anti-inflammatory agent) as monotherapies in AD. We have previouly shown that combination treatment of L+P in APP/PS1 mice at the onset of pathology significantly improved memory and reduced brain A{beta} levels relative to control mice. In this new study, we sought to replicate our previous findings in a new cohort of APP/PS1 mouse to further confirm whether the combined treatment of L+P is superior to each treatment individually. MethodsWe have re-evaluated the effects of L+P co-treatment in APP/PS1 mice using thioflavin-S staining, MOA{beta} immunolabeling and enzyme-linked immunosorbent assay (ELISA) to examine effects on A{beta} levels and pathology, relative to animals that received L or P individually. To explore mechanism of regulation, we used Western blotting to examine the expression of the peroxisome-proliferator activated receptor {gamma} (PPAR{gamma}), due to its potential role in the regulation of the inflammatory response. ResultsWe demonstrated that combining L and P significantly enhances the anti-A{beta} effect of L or P in the hippocampus of APP/PS1 mice. Western blot analysis indicated that A{beta} reduction was accompanied by up-regulation of the PPAR{gamma} levels. ConclusionOur findings suggest that combining L and P significantly enhances the anti-A{beta} effect of L or P in the hippocampus of APP/PS1 mice, and may be a potential new effective strategy for AD therapy.

neuroscience↗