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Le Grazie di Ancona, Italy

Nasuti C.,University of Camerino | Fattoretti P.,Cellular Bioenergetics Laboratory | Carloni M.,University of Camerino | Fedeli D.,University of Camerino | And 3 more authors.
Journal of Neurodevelopmental Disorders | Year: 2014

Background: During the neurodevelopmental period, the brain is potentially more susceptible to environmental exposure to pollutants. The aim was to determine if neonatal exposure to permethrin (PERM) pesticide, at a low dosage that does not produce signs of obvious abnormalities, could represent a risk for the onset of diseases later in the life. Methods: Neonatal rats (from postnatal day 6 to 21) were treated daily by gavage with a dose of PERM (34 mg/kg) close to the no-observed-adverse-effect level (NOAEL), and hippocampal morphology and function of synapses were investigated in adulthood. Fear conditioning, passive avoidance and Morris water maze tests were used to assess cognitive skills in rats, whereas electron microscopy analysis was used to investigate hippocampal morphological changes that occurred in adults. Results: In both contextual and tone fear conditioning tests, PERM-treated rats showed a decreased freezing. In the passive avoidance test, the consolidation of the inhibitory avoidance was time-limited: the memory was not impaired for the first 24 h, whereas the information was not retained 72 h following training. The same trend was observed in the spatial reference memories acquired by Morris water maze. In PERM-treated rats, electron microscopy analysis revealed a decrease of synapses and surface densities in the stratum moleculare of CA1, in the inner molecular layer of the dentate gyrus and in the mossy fibers of the hippocampal areas together with a decrease of perforated synapses in the stratum moleculare of CA1 and in the inner molecular layer of the dentate gyrus. Conclusions: Early-life permethrin exposure imparts long-lasting consequences on the hippocampus such as impairment of long-term memory storage and synaptic morphology. © 2014 Nasuti et al.; licensee BioMed Central Ltd.

Mariotti R.,University of Verona | Fattoretti P.,Cellular Bioenergetics Laboratory | Malatesta M.,University of Verona | Nicolato E.,University of Verona | And 2 more authors.
Journal of Nutrition, Health and Aging | Year: 2014

Objectives: To assess the effect of mild forced physical training on cerebral blood volume (CBV) and other brain parameters in old mice. Setting: Treadmill in the animal house. Participants: Thirty old (>25 mo) male mice were randomly assigned to one of three groups, exercise (E), exercise plus testosterone (T) (ET), and rest (C). Intervention: Mild physical training on treadmill (30 min a day at belt speed = 8 m/min, five days a week) with or without one weekly injection of testosterone. Measurements: CBV, quantitative transverse relaxation time (T2) maps, and cortical thickness were measured by magnetic resonance imaging. Results: A significant increase of CBV was found in the motor and hippocampal cortex of E and ET mice; cortical thickness was not affected. T2 maps analysis suggested that water distribution did not change. T administration did not add to the effect of physical training. Conclusion: This work provides first quantitative evidence that exercise initiated at old age is able to improve the hemodynamic status of the brain cortex in key regions for movement and cognition without inducing edema.

Balietti M.,Neurobiology of Aging Laboratory | Balietti M.,Cellular Bioenergetics Laboratory | Casoli T.,Neurobiology of Aging Laboratory | Di Stefano G.,Neurobiology of Aging Laboratory | And 4 more authors.
Ageing Research Reviews | Year: 2010

Ketogenic diets (KDs), successfully used in the therapy of paediatric epilepsy for nearly a century, have recently shown beneficial effects also in cancer, obesity, diabetes, GLUT 1 deficiencies, hypoxia-ischemia, traumatic brain injuries, and neurodegeneration. The latter achievement designates aged individuals as optimal recipients, but concerns derive from possible age-dependent differences in KDs effectiveness. Indeed, the main factors influencing ketone bodies utilization by the brain (blood levels, transport mechanisms, catabolic enzymes) undergo developmental changes, although several reports indicate that KDs maintain some efficacy during adulthood and even during advanced aging. Encouraging results obtained in patients affected by age-related neurodegenerative diseases have prompted new interest on KDs' effect on the aging brain, also considering the poor efficacy of therapies currently used. However, recent morphological evidence in synapses of late-adult rats indicates that KDs consequences may be even opposite in different brain regions, likely depending on neuronal vulnerability to age. Thus, further studies are needed to design KDs specifically indicated for single neurodegenerative diseases, and to ameliorate the balance between beneficial and adverse effects in aged subjects. Here we review clinical and experimental data on KDs treatments, focusing on their possible use during pathological aging. Proposed mechanisms of action are also reported and discussed. © 2010 Elsevier Ireland Ltd. All rights reserved.

Malatesta M.,University of Verona | Fattoretti P.,Cellular Bioenergetics Laboratory | Giagnacovo M.,University of Pavia | Pellicciari C.,University of Pavia | Zancanaro C.,University of Verona
Rejuvenation Research | Year: 2011

Aging is associated with a progressive loss of muscle mass, strength, and function, a condition known as sarcopenia, which represents an important risk factor for physical disability in elderly. The mechanisms leading to sarcopenia are still largely unknown, and no specific therapy is presently available to counteract its onset or progress. Many studies have stressed the importance of physical exercise as an effective approach to prevent/limit the age-related muscle mass loss. This study investigated the effects of physical training on pre-mRNA pathways in quadriceps and gastrocnemius muscles of old mice by ultrastructural cytochemistry: Structural and in situ molecular features of myonuclei and satellite cell nuclei of type II fibers were compared in exercised versus sedentary old mice, using adult individuals as control. Our results demonstrated that in myonuclei of old mice physical exercise stimulates pre-mRNA transcription, splicing, and export to the cytoplasm, likely increasing muscle protein turnover. In satellite cells, the effect of physical exercise seems to be limited to the reactivation of some factors involved in the transcriptional and splicing apparatus without increasing RNA production, probably making these quiescent cells more responsive to activating stimuli. © 2011 Mary Ann Liebert, Inc.

Casoli T.,Neurobiology of Aging Laboratory | Di Stefano G.,Neurobiology of Aging Laboratory | Fattoretti P.,Neurobiology of Aging Laboratory | Fattoretti P.,Cellular Bioenergetics Laboratory | And 7 more authors.
Neurobiology of Aging | Year: 2012

Previous studies have shown that messenger RNA (mRNA) of the dynamin-binding protein (DNMBP), a scaffold protein regulating actin cytoskeleton and synaptic vesicle pools, is lower in neuropathologically-confirmed Alzheimer's brains. Here we investigated whether a deficit in long term memory formation during physiological aging is also associated with lower DNMBP expression. Hippocampal DNMBP mRNA was quantified by quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) following inhibitory avoidance task in aged (26- to 27-month-old) rats that, according to memory performance, were ranked as good responders (GR) and bad responders (BR), in adult (3-month-old), late-adult (19-month-old), and aged (26-27-month-old) naive animals. We found that DNMBP mRNA levels were significantly higher in naive adults versus late adult and aged naive rats, in GR versus BR, and in pooled GR and BR versus aged-matched controls. Our data provide the first evidence that hippocampal DNMBP mRNA expression is reduced during physiological aging, and suggest that the capability to increase the expression of this mRNA may be a requirement for preserving long term memory formation during aging. © 2012 Elsevier Inc.

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