Building an experimental nutritional model of obesity. Evaluation of anthropometrical and nutritional parameters

The etiology of obesity is multifactorial, and includes genetic, environmental, and dietary factors, where hypercaloric diets play a central role in the development of the disease. It is known that obesity in adulthood can increase the risk of suffering neurodegenerative diseases. As a part of an institutional project that studies obesity as a base disease for the development of chronic age-associated diseases and the search for early biomarkers with predictive potential, one of our general objectives is to establish a nutritional model of obesity in rat. Particularly, the objective of this work was to evaluate the effects of a high saturated fat diet on different anthropometric and nutritional parameters. Male Wistar rats weaned at 21 days of age were fed with a normocaloric diet (ND) containing 366 kcal from lipids/kg diet. At 2 months old, they were randomly separated and fed with the NC diet (Control group) and a high saturated fat diet containing 1570.7 kcal from margarine/kg diet (HFD group) for the following 14 weeks. Animals were maintained under 12 h light:12 h dark and 22–24°C conditions, with food and water ad libitum. The anthropometric profile included the evaluation of food intake, body weight, body mass index (BMI), weight gain, dietary consumption, and Lee index, throughout the entire treatment period. The following nutritional parameters were also calculated: energy-intake, and feed efficiency. Statistical differences between groups and throughout the treatment period were analyzed by two-way ANOVA, followed by Bonferroni post-hoc test, with P < 0.05 to confirm significant differences between groups and weeks. Our results show that feeding HFD resulted in significant increases in the following anthropometric parameters: body weight (P < 0.001 from the 9th to the 21st week), BMI (P < 0.05 from the 14th to the 22nd week), weight gain (P < 0.05 from the 15th to the 22nd week) as well as in the nutritional parameter: energy-intake from lipids (P < 0.001 from the 9th to the 22nd week). We did not observe significant changes in food intake, Lee index, feed efficiency nor in the total energy intake. Thus, we could conclude that a high saturated fat, from margarine, diet modifies key anthropometrical and nutritional parameters, and it could be used to establish a nutritional model of obesity in rat.Fil: Alfonso, Javier Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Lopez, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Delgado, Silvia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaIV Reunión Conjunta de Sociedades de Biología de la República Argentina: “Nuevas Evidencias y Cambios de Paradigmas en Ciencias Biológicas”ArgentinaSociedad de Biología de CuyoUniversidad Nacional de CuyoSociedad Argentina de BiologíaSociedad de Biología de CórdobaSociedad de Biología de RosarioAsociación de Biología de TucumánHonorable Legislatura de la Provincia de MendozaSociedad Chilena de Reproducción y DesarrolloMinisterio de Salud Provincia de MendozaGobierno de la Provincia de Mendoz

Effect of a pparγ synthetic agonist associated with retinoic acid on 24-hour rhythms in the hippocampus of an experimental model of Alzheimer’s disease

Alzheimer's disease (AD) is the most frequent cause of dementia in the older adults. The main pathogenic mechanism in sporadic AD is the decreasein amyloid beta peptide (Aβ) clearance. It is known that Apolipoprotein E (Apo E) modulates Aβ deposition and clearance. ApoE expression istranscriptionally induced by PPARγ in coordination with RXRs. Previously, we found that an intracerebroventricular injection of Aβ(1-42) modifiedthe daily rhythms of Apo E, Bmal 1, and Aβ in the rat hippocampus. Taking into account those observations, the objective of this work was toinvestigate the effects of synthetic PPARγ agonist, pioglitazone, and retinoic acid (Pio-RA) on the 24-h rhythms of Apo E, BMAL1 and Aβ proteinlevels, as well as on the daily rhythms of brain-derived neurotrophic factor (Bdnf) and its receptor (TrkB) expression in the rat hippocampus. In thisstudy, male Holtzman rats from control, Aβ-injected (Aβ) and Aβ-injected treated with Pio-RA groups were euthanized throughout a 24-h period andhippocampus samples were isolated every 6 h. Apo E, BMAL1 and Aβ proteins levels were analyzed by immunoblotting and Bdnf and TrkB mRNAlevels were determined by RT-PCR. Regulatory regions of Apo E and clock genes were scanned for E-box, RORE, RXRE and PPRE sites. Weobserved that the treatment of Pio-RA reestablished the daily rhythms of Apo E, Aβ, BMAL1 protein, and Bdnf mRNA levels. This treatment alsoincreased Bdnf and TrkB levels. We found E-box, RXRE, and PPRE sites on regulatory regions of Apo E and Bmal1 genes. The results of thepresent study could suggest that the treatment of Pio-RA would not only restore the altered rhythmic patterns of the clock genes and their target genesobserved in animals injected with Aβ aggregates, but also, interestingly, would increase the levels of cognition-related genes, which are decreased inAlzheimer's patients.Fil: Castro, A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Mazaferro, P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Golini, Rebeca Laura Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaXXXVII Annual Scientific Meeting of the Tucumán Biology Association XXIII Annual Scientific Meeting of the Córdoba Biology Society XXXVIII Annual Scientific Meeting of the Cuyo Biology Society Argentine Biology SocietyArgentinaSociedades de Biología de la República Argentin

An intracerebroventricular injection of AΒ (1–42) modifies temporal profiles of spatial memory performance and oxidative status in the temporal cortex rat

Alzheimer´s dementia (AD) is a neurodegenerative disorder that causes memory loss and dementia in older adults. Intracellular accumulation of Aβ causes an imbalance in the oxidative status and cognitive dysfunctions. Besides oxidative stress and loss of memory, Alzheimer´s patients show dysfunction of the circadian rhythms. The objective of this work was to evaluate the consequences of an intracerebroventricular injection of Aβ (1-42) on temporal patterns of cognitive performance, as well as on lipid peroxidation, protein oxidation and total antioxidant capacity levels, in the rat temporal cortex. Holtzman male rats from control and Aβ-injected groups were used in this study. We found that MDA, protein carbonyls and total antioxidant capacity levels displayed day-night oscillations in the rat temporal cortex and spatial memory performance also varied rhythmically. An intracerebroventricular injection of Aβ (1-42) modified temporal patterns of cognitive performance as well as daily profiles of parameters of oxidative stress. Thus, elevated levels of Aβ aggregates induces alterations in daily rhythmicity of parameters of oxidative stress and, consequently, would affect cellular clock activity, affecting the spatial memory performance in the AD.Fil: Coria Lucero, Cinthia Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Castro, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ledezma, Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Leporatti, Jorge. Universidad Nacional de San Luis; ArgentinaFil: Ramirez, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ghersi, Marisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Delgado, Silvia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

An intracerebroventricular injection of amyloid-beta peptide (1–42) aggregates modifies daily temporal organization of clock factors expression, protein carbonyls and antioxidant enzymes in the rat hippocampus

Alzheimer disease (AD) is the most frequent form of dementia in the elderly. It is characterized by the deterioration of memory and learning. The histopathological hallmarks of AD include the presence of extracellular deposits of amyloid beta peptide, intracellular neurofibrillary tangles, neuron and synapse loss, in the brain, including the hippocampus. Accumulation of Aβ peptide causes an increase in intracellular reactive oxygen species (ROS) and free radicals associated to a deficient antioxidant defense system. Besides oxidative stress and cognitive deficit, AD patients show alterations in their circadian rhythms. The objective of this work was to investigate the effects of an intracerebroventricular injection of amyloid beta peptide Aβ(1–42) aggregates on temporal patterns of protein oxidation, antioxidant enzymes and clock factors in the rat hippocampus. Four-month-old male Holtzman rats divided into the groups control (CO) and Aβ-injected (Aβ), were maintained under 12 h-light12h-dark conditions and received water and food ad-libitum. Hippocampus samples were isolated every 6 h during a 24 h period. Our results showed daily patterns of protein carbonyls, catalase (CAT) and glutathione peroxidase (GPx) expression and activity, as well as Rorα and Rev-erbß mRNA, in the rat hippocampus. Interestingly, an intracerebroventricular injection of Aβ aggregates modified daily oscillation of protein carbonyls levels, phase-shifted daily rhythms of clock genes and had a differential effect on the daily expression and activity of CAT and GPx. Thus, Aβ aggregates might affect clock-mediated transcriptional regulation of antioxidant enzymes, by affecting the formation of BMAL1:CLOCK heterodimer, probably, as a consequence of the alteration of the redox state observed in rats injected with Aβ.Fil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Alfaro, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Mazaferro, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Golini, Rebeca Laura Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Leporatti, Jorge. Universidad Nacional de San Luis. Facultad de Ciencias Económicas, Jurídicas y Sociales; ArgentinaFil: Della Vedova, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Delsouc, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Casais, Marilina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet

Objectives: Alterations in enzymatic antioxidant defense systems lead to a deficit of cognitive functions and altered hippocampal synaptic plasticity. The objectives of this study were to investigate endogenous rhythms of catalase (CAT) and glutathione peroxidase (GPx) expression and activity, as well as CREB1 mRNA, in the rat hippocampus, and to evaluate to which extent the vitamin A deficiency could affect those temporal patterns. Methods: Rats from control and vitamin A-deficient (VAD) groups received a diet containing 4000 IU of vitamin A/kg diet, or the same diet devoid of vitamin A, respectively, during 3 months. Rats were maintained under 12-hour-dark conditions, during 10 days before the sacrifice. Circadian rhythms of CAT, GPx, RXRγ, and CREB1 mRNA levels were determined by reverse transcriptrase polymerase chain reaction in hippocampus samples isolated every 4 hours during a 24-hour period. CAT and GPx enzymatic activities were also determined by kinetic assays. Regulatory regions of clock and antioxidant enzymes genes were scanned for E-box, RXRE, and CRE sites. Results: E-box, RXRE, and CRE sites were found on regulatory regions of GPx and CAT genes, which display a circadian expression in the rat hippocampus. VAD phase shifted CAT, GPx, and RXRγ endogenous rhythms without affecting circadian expression of CREB1. Discussion: CAT and GPx expression and enzymatic activity are circadian in the rat hippocampus. The VAD affected the temporal patterns antioxidant genes expression, probably by altering circadian rhythms of its RXR receptors and clock factors; thus, it would impair the temporal orchestration of hippocampal daily cognitive performance.Fil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Delgado, Silvia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gimenez, Maria Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Circadian rhythms of locomotor activity and hippocampal clock genes expression are dampened in vitamin A-deficient rats

The main external time giver is the day-night cycle; however, signals from feeding and the activity/rest cycles can entrain peripheral clocks, such as the hippocampus, in the absence of light. Knowing that vitamin A and its derivatives, the retinoids, may act as regulators of the endogenous clock activity, we hypothesized that the nutritional deficiency of vitamin A may influence the locomotor activity rhythm as well as the endogenous circadian patterns of clock genes in the rat hippocampus. Locomotor activity was recorded during the last week of the treatment period. Circadian rhythms of clock genes expression were analyzed by reverse transcription–polymerase chain reaction in hippocampus samples that were isolated every 4 hours during a 24-hour period. Reduced glutathione (GSH) levels were also determined by a kinetic assay. Regulatory regions of clock PER2, CRY1, and CRY2 genes were scanned for RXRE, RARE, and RORE sites. As expected, the locomotor activity pattern of rats shifted rightward under constant dark conditions. Clock genes expression and GSH levels displayed robust circadian oscillations in the rat hippocampus. We found RXRE and RORE sites on regulatory regions of clock genes. Vitamin A deficiency dampened rhythms of locomotor activity as well as modified endogenous rhythms of clock genes expression and GSH levels. Thus, vitamin A may have a role in endogenous clock functioning and participate in the circadian regulation of the cellular redox state in the hippocampus, a peripheral clock with relevant function in memory and learning.Fil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaFil: Delgado, Silvia M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Golini, Rebeca Laura Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentin

Effects of experimental intracerebral ventricular injection of amyloid beta peptide (1-42) aggregates on daily rhythms of Aβ-degrading enzymes in the hippocampus: Relevance to Alzheimer's disease pathophysiology

One of the main pathological features in the Alzheimer disease (AD) is the presence of senile plaques, primarily composed of Aβ peptide aggregates, in cortex and hippocampus. AD late onset, which constitutes 90% of cases, could be mainly attributable to deficiencies in the clearance of the Aß peptide. Here we show that expression of Aβ-degrading enzymes varies on a daily basis in the hippocampus. Interestingly, an intracerebroventricular injection of Aβ aggregates modified temporal patterns of Aβ-degrading proteases, as well as clock proteins (BMAL1 and RORα) and antioxidant enzymes (CAT and GPx) daily rhythms. Our findings showed that the increase of Aβ leads to the alteration of the enzymes involved in the clearance, and, consequently, to an increase of oxidative stress and alteration of the cellular redox state, affecting the functioning of the endogenous clock and daily rhythms of BMAL1, RORα and their target genes, in this disease.Fil: Castro, Andrea Grisel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Coria Lucero, Cinthia Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Daily rhythms of cognition-related factors are modified in an experimental model of Alzheimer's disease

The accumulation of amyloid-β (Aβ) peptides in the brain of Alzheimer disease patients is associated to cognitive deficit, increased oxidative stress, and alterations in the circadian rhythms. Brain-derived neurotrophic factor (BDNF) and Neurogranin (RC3), play an important role in the synaptic plasticity underlying memory and learning. Previously, we observed BDNF and RC3 expression follow a daily rhythmic pattern in the hippocampus of young rats. The objective of this study was to investigate the effects of an intracerebroventricular (i.c.v) injection of aggregated Aβ peptide (1–42) on temporal patterns of ApoE protein, Bdnf and Rc3 mRNA, lipid peroxidation (LPO) and reduced glutathione (GSH) levels, in the rat hippocampus. We observed an i.c.v. injection of Aβ aggregates phase shifts daily BDNF and RC3 expression as well as LPO and decreased the mesor of GSH rhythms. ApoE protein levels vary rhythmically throughout the day. ApoE levels increase at ZT 03:39 ± 00:22 in the hippocampus of control rats and at ZT 06:30 ± 00:28 in the treated animals. Thus, elevated levels of Aβ aggregates, characteristic of AD, altered temporal patterns of cognition related-factors, probably, as a consequence of changes in the daily variation of ApoE-mediated Aβ aggregates clearance as well as in the 24 h rhythms of the cellular redox state.Fil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Castro, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Pignataro, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Garraza, Marisa Hilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Casais, Marilina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich Miranda, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Aging abolishes circadian rhythms of RORα and antioxidant enzymes expression in temporal cortex of free running rats

RORα is a transcription factor that binds RORE motifs in the promoter of clock Bmal1 and othertarget genes. Antioxidant enzymes contribute to the cellular redox state which is crucial for themolecular clock function. Previously, we showed antioxidant enzymes activity follow a dailyvariation in temporal cortex (TC), which was abolished in aged rats. Herein we aimed: 1) toinvestigate endogenous rhythms of Cat, Gpx and Nrf2 genes expression and RORα protein levels inrat TC, and 2) to evaluate whether aging could affect those temporal patterns. Three- and 22-monthold male Holtzman rats were maintained under constant darkness for 15 days before the experiment,in order to validate the endogenous nature of circadian rhythms. TC samples were isolated every 4h during a 24h period. RORα protein levels were assessed by immunoblotting. Cat, Gpx and Nrf2 mRNA levels were determined by RT-PCR. Specific softwares were used to circadian analysis. We observed circadian endogenous rhythms of RORα, Cat and Gpx expression in the TC of young freerunning rats (Chronos fit, p<0.05, p< 0.001 and p<0.05, respectively). We found Ebox and RORE sites in the Cat and Gpx genes regulatory regions. RORα rhythm?s acrophase occurs at the beginning of the subjective day, preceding Cat and Gpx mRNA peaks. Consistent with previous results, aging abolishes RORα, Cat, and Gpx circadian rhythms in TC. Interestingly, Nrf2 gene expression becomes rhythmic in the TC of aged rats. Our observations would contribute to the knowledge of circadian alterations in TC of the aged brain.Fil: Deyurka, Nicolás Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Coria Lucero, Cinthia Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Lacoste, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Anzulovich, A. C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaXXXV Reunión Científica Anual de la Sociedad de Biología de CuyoVilla de MerloArgentinaSociedad de Biología de Cuy

Chronobiological study of physiological variables and antioxidant metabolism in glicine max

The Earth rotation exposes most of the planet's species to the environmental daily oscillations. These external oscillations synchronize the internal biological clocks that generate biological rhythms in the organisms, to anticipate the environmental changes. Among these rhythms, the circadian, 24h-rhythms, are the most studied. In plants, the initiation of photosynthesis after sunrise (periodic process) triggers the accumulation of metabolites, including the production of reactive oxygen species (ROS). ROS represent a constant threat to plants, as they react with different cellular components generating oxidative stress. However, plants have developed mechanisms to maintain redox homeostasis. The oscillations in ROS production, removal and signaling would involve the plant biological clock. The functions of clock oscillators in agriculturally important species, such as soybean (Glycine max L.), are increasingly recognized. Soybean is one of the most important and cultivated legumes in the world and constitutes the main export item of Argentina, one of the main producing countries worldwide. Therefore, the objective of this work was to study the influence of the biological clock on the physiology and antioxidant metabolism of Glycine max L. throughout a 24-hour period. For this purpose, soybean cultures were grown in hydroponics for 7 days under standard environmental conditions, with a 14h-light:10h-dark photoperiod. Biochemical (antioxidant enzyme activity, lipid peroxidation and H2O2 levels), physiological (photosynthetic pigment concentration) and molecular (primer design, identification of transcription factor binding sites) parameters, were determined in soybean leaves. Interestingly, we found that Catalase activity (p<0.05), H2O2 levels (p<0.01) and the content of chlorophyll a (p<0.01) and total chlorophyll (p<0.05) display significant daily rhythms in this tissue (Chronos-fit, p<0.05, p<0.05, p<0.05 y p<0.01, and % rhythm: 66.36%, 55.12%, 39.87%, 48.58%, respectively), with their acrophases occurring at ZT 04:18 ± 00:29, ZT 04:53 ± 00:59, ZT 10:41 ± 03:03 y ZT 10:41 ± 01:28, respectively. Even though, carotenoid content shows a significant daily variation (p<0.05), it does not adjust to a cosine curve and therefore, cannot be define as a rhythm. The 24-h oscillations showed here, might suggest the regulation of oxidative metabolism by the biological clock, in the leaves of Glycine max L. an agriculturally important plant. These results would provide useful information for plant manipulation and crop management, taking into account how antioxidant defenses and oxidative stress vary throughout the day.Fil: Pardo DAniela. Universidad Nacional de San Luis; ArgentinaFil: Gatica CV. Universidad Nacional de San Luis; ArgentinaFil: Anzulovich AC.. Universidad Nacional de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Universidad Nacional de San Luis; ArgentinaFil: Molina As. Universidad Nacional de San Luis; ArgentinaFil: Golini Rebeca. Universidad Nacional de San Luis; ArgentinaFil: Perez Chaca, Maria Veronica. Universidad Nacional de San Luis; ArgentinaXXXIX Reunión Científica Anual de la Sociedad de Biología de CuyoArgentinaSociedad de Biología de Cuy