Cellular Bioenergetics Laboratory

Ancona, Italy

Cellular Bioenergetics Laboratory

Ancona, Italy
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Casoli T.,Neurobiology of Aging Center | Balietti M.,Neurobiology of Aging Center | Balietti M.,Cellular Bioenergetics Laboratory | Giorgetti B.,Neurobiology of Aging Center | And 5 more authors.
Current Pharmaceutical Design | Year: 2013

Alzheimer's disease (AD) is a complex degenerative disorder of the brain, associated with a progressive cognitive decline. Age is the main risk factor with almost half of the population above 90 years affected by this pathology. AD and brain aging share common molecular changes, so it has been hypothesized that AD could be a form of accelerated brain aging. In this context, senescence-associated mechanisms could be a valuable target of investigation both to analyze the causes of this disease and to define therapeutic strategies. Senescent phenotypes of glia and neurons, as well as of peripheral cells, have been described in AD. Much evidence indicate that vascular impairment is a fundamental contributor to AD pathology and platelets are generally considered a key element because they represent the link between amyloid-ß (Aß) deposition, peripheral inflammation and endothelial senescence. Both activated and senescent platelets are a source of Aß, in addition activated platelets secrete many proinflammatory mediators that could contribute to increased peripheral inflammation and endothelial senescence. Treatments aimed to target peripheral endothelial senescence include antioxidants and some substances, such as aspirin, that modulate platelet aggregation and inflammatory response. Heparin has been proposed as a treatment for senile dementia and exhibits anti-inflammatory action as well as inhibitory effects on Aß assembly. Identifying peripheral targets for AD treatments could also result advantageous as it would be possible to monitor directly their efficacy. Nevertheless more research is needed to clarify all the different aspects and interactions of blood cells, vascular cells and their secretory products. © 2013 Bentham Science Publishers.


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.


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.


Casoli T.,Neurobiology of Aging Center | Di Stefano G.,Neurobiology of Aging Center | Balietti M.,Neurobiology of Aging Center | Balietti M.,Cellular Bioenergetics Laboratory | And 5 more authors.
Biogerontology | Year: 2010

Alzheimer's disease is an age-dependent neurodegenerative disorder characterized by loss of neurons, synaptic degeneration, senile plaques and neurofibrillary tangles. Besides these hallmarks, increased accumulation of activated microglia, astrocytes and leukocytes adhering to postcapillary venules are observed in the affected brain areas, suggesting the presence of an ongoing inflammatory process. As neuroinflammation triggers the activation of peripheral immune system, many studies have analyzed circulating inflammatory biomarkers, including basal or stimulated levels of cytokines and related molecules in blood of Alzheimer's patients, but with conflicting results. Platelets are an important source of amyloid- (A) in the circulatory system and play an important pro-inflammatory role. Upon activation, they adhere to leukocytes and endothelial cells by means of adhesive proteins like P-selectin, platelet endothelial cell adhesion molecule-1 (PECAM) and intercellular adhesion molecule-1 and -2 (ICAM-1 and -2) and secrete inflammatory mediators (chemokines, interleukins). In addition, platelets contain important enzymes involved in inflammatory intermediary synthesis like phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2), and recent reports demonstrated significant changes in platelet levels and activities in Alzheimer's disease. Thus, as platelets represent an important link between A deposition and inflammatory reactions especially at endothelial level, they can be considered a valuable cellular model to evaluate potential peripheral inflammatory biomarkers in Alzheimer's disease. © 2010 Springer Science+Business Media B.V.


Balietti M.,Neurobiology of Aging Laboratory | Balietti M.,Cellular Bioenergetics Laboratory | Tamagnini F.,University of Bologna | Fattoretti P.,Neurobiology of Aging Laboratory | And 6 more authors.
Rejuvenation Research | Year: 2012

Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. © 2012 Mary Ann Liebert, Inc.


Tamagnini F.,University of Bologna | Burattini C.,University of Bologna | Casoli T.,Neurobiology of Aging Laboratory | Balietti M.,Neurobiology of Aging Laboratory | And 4 more authors.
Rejuvenation Research | Year: 2012

Visual recognition memory is early impaired in Alzheimer's disease. Long-term depression of synaptic transmission in the perirhinal cortex is critically involved in this form of memory. We found that synaptic transmission was impaired in perirhinal cortex slices obtained from 3-month-old Tg2576 mice, and that 3,000 pulses at 5Hz induced long-term depression in perirhinal cortex slices from age-matched control mice, but not in those from Tg2576 mice. To our knowledge, these data provide the first evidence of synaptic transmission and long-term depression impairment in the perirhinal cortex in an animal model of Alzheimer's disease, and the earliest synaptic deficit in Tg2576 mice. © 2012 Mary Ann Liebert, Inc.


Balietti M.,Neurobiology of Aging Center | Balietti M.,Cellular Bioenergetics Laboratory | Giorgetti B.,Neurobiology of Aging Center | Casoli T.,Neurobiology of Aging Center | And 7 more authors.
Journal of Alzheimer's Disease | Year: 2013

Increasing experimental evidence indicates that synaptic alterations play a key role in cognitive decline in Alzheimer's disease (AD). Functional and structural synaptic changes progressively take place, beginning in the early phase of AD, mainly triggered by intracellular accumulation of soluble amyloid-β (Aβ) oligomers. These peptides also accumulate within mitochondria, heavily affecting their function and morphology, particularly in synaptic compartments. To better understand the role of mitochondrial impairment in synaptic alterations during the early stages of AD, a morphological investigation was performed by means of electron microscopy in the hippocampus of 3 month-old Tg2576 and transgene-negative littermate mice. In the stratum moleculare of CA1 pyramidal cells (SMCA1) of transgenic animals compared to controls, we found significantly larger and less numerous synapses, with a significantly reduced fraction of the perforated subtype, as well as significantly smaller and more numerous mitochondria. In contrast, no differences between the two groups of mice were found in the inner molecular layer of the dentate gyrus. The reduction of synaptic contacts in SMCA1 indicates a precocious vulnerability of this region, and the synaptic enlargement may reflect a compensating process aimed at maintaining the overall contact density. Accordingly, mitochondrial modifications may represent a plastic reactive phenomenon aimed at sustaining the increased energy needs for synaptic remodeling, since mitochondrial morphology was perfectly preserved and smaller mitochondria are metabolically more efficient. Thus, morphological changes occurring at synaptic level in SMCA1 of 3 month-old Tg2576 mice might reflect a precocious vulnerability associated with a residual plastic reactivity which may slow down functional alterations. © 2013 - IOS Press and the authors. 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.


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.


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.

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