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Ozzano dell'Emilia, Italy

Tomasini M.C.,University of Ferrara | Borelli A.C.,University of Ferrara | Beggiato S.,University of Ferrara | Ferraro L.,University of Ferrara | And 5 more authors.
Journal of Alzheimer's Disease | Year: 2015

Background: Considering the heterogeneity of pathological changes occurring in Alzheimer's disease (AD), a therapeutic approach aimed both to neuroprotection and to neuroinflammation reduction may prove effective. Palmitoylethanolamide (PEA) has attracted attention for its anti-inflammatory/neuroprotective properties observed in AD animal models. Objective and Methods: We evaluated the protective role of PEA against amyloid-β42 (Aβ42) toxicity on cell viability and glutamatergic transmission in primary cultures of cerebral cortex neurons and astrocytes from the triple-transgenic murine model of AD (3xTg-AD) and their wild-type littermates (non-Tg) mice. Results: Aβ42 (0.5μM; 24h) affects the cell viability in cultured cortical neurons and astrocytes from non-Tg mice, but not in those from 3xTg-AD mice. These effects were counteracted by the pretreatment with PEA (0.1 μM). Basal glutamate levels in cultured neurons and astrocytes from 3xTg-AD mice were lower than those observed in cultured cells from non-Tg mice. Aβ42-exposure reduced and increased glutamate levels in non-Tg mouse cortical neurons and astrocytes, respectively. These effects were counteracted by the pretreatment with PEA. By itself, PEA did not affect cell viability and glutamate levels in cultured cortical neurons and astrocytes from non-Tg or 3xTg-AD mice. Conclusion: The exposure to Aβ42 induced toxic effects on cultured cortical neurons and astrocytes from non-Tg mice, but not in those from 3xTg-AD mice. Furthermore, PEA exerts differential effects against Aβ42-induced toxicity in primary cultures of cortical neurons and astrocytes from non-Tg and 3xTg-AD mice. In particular, PEA displays protective properties in non-Tg but not in 3xTg-AD mouse neuronal cultured cells overexpressing Aβ. © 2015-IOS Press and the authors. Source

Beggiato S.,University of Ferrara | Antonelli T.,University of Ferrara | Tomasini M.C.,IRET Foundation | Tomasini M.C.,University of Ferrara | And 6 more authors.
Current Protein and Peptide Science | Year: 2014

Striatal dopamine adenosine A2A and D2 receptors interact to modulate some aspects of motor and motivational function. The demonstration of A2A/D2 receptor heteromerization in living cells constituted a progress for understanding the neurobiology of dopamine D2 and adenosine A2A receptors. In fact, the existence of putative striatalA2A/D2 receptor heteromers has been suggested to be important for striatal function under both normal and pathological conditions, such as Parkinson’s disease. Consequently, the antagonistic A2A-D2 receptor interactions in a putative striatal receptor heteromer on striato-pallidal GABA neuron led to the introduction of A2A receptor antagonists as possible anti- Parkinsonian drugs. The present mini-review briefly summarizes the main findings supporting the presence of antagonistic A2A-D2 receptor interactions in putative receptor heteromers in the basal ganglia. Special emphasis is given to in vivo microdialysis findings demonstrating the functional role putative A2A/D2 heteromers on striato-pallidal GABA neurons play in the modulation of this pathway, in which A2A receptors inhibit D2 receptor signaling. The possible relevance of compounds targeting the putative striatal A2A/D2 heteromer in the Parkinson’s disease pharmacological treatment is also discussed. © 2014 Bentham Science Publishers Source

Beggiato S.,University of Ferrara | Giuliani A.,University of Bologna | Sivilia S.,University of Bologna | Lorenzini L.,University of Bologna | And 5 more authors.
Neuroscience | Year: 2014

CHF5074 is a nonsteroidal anti-inflammatory derivative that has been shown to inhibit β-amyloid plaque deposition and to reverse memory deficit in vivo in transgenic mouse models of Alzheimer's disease (AD).In the present in vivo study we used pre-plaque Tg2576 mice showing cognitive impairments to investigate the effects of a sub-acute treatment with CHF5074 on prefrontal cortex dialysate glutamate levels. Furthermore, the effects of CHF5074 have been compared with those induced, under the same experimental conditions, by LY450139, a potent γ-secretase inhibitor, that has been shown to inhibit brain β-amyloid production. No differences in prefrontal cortex dialysate glutamate levels were observed between control Tg2576 and wild-type animals. A sub-acute (8. days) treatment with CHF5074 (30. mg/kg, s.c.), LY450139 (3. mg/kg, s.c.) or their respective vehicles did not modify prefrontal cortex dialysate glutamate levels. After these treatments, the injection of CHF5074 reduced, while LY450139 increased, prefrontal cortex dialysate glutamate levels in Tg2576 mice, but not in wild-type animals. These results suggest that at the dose tested CHF5074 and LY450139 differently affect cortical glutamate transmission in pre-plaque Tg2576 mice. This different neurochemical profile could be involved in the different ability of the two drugs in improving early cognitive performance in this animal model of AD. © 2014 IBRO. Source

Baratto L.,La Colletta Bioengineering Center | Calza L.,IRET Foundation | Calza L.,University of Bologna | Capra R.,La Colletta Bioengineering Center | And 5 more authors.
Lasers in Medical Science | Year: 2011

A growing number of laboratory and clinical studies over the past 10 years have shown that low-level laser stimulation (633 or 670 nm) at extremely low power densities (about 0.15 mW/cm2), when administered through a particular emission mode, is capable of eliciting significant biological effects. Studies on cell cultures and animal models as well as clinical trials give support to a novel therapeutic modality, which may be referred to as ultra low level laser therapy (ULLLT). In cultured neural cells, pulsed irradiation (670 nm, 0.45 mJ/cm2) has shown to stimulate NGF-induced neurite elongation and to protect cells against oxidative stress. In rats, anti-edema and antihyperalgesia effects following ULLL irradiation were found. Clinical studies have reported beneficial effects (also revealed through sonography) in the treatment of musculoskeletal disorders. The present paper reviews the existing experimental evidence available on ULLLT. Furthermore, the puzzling issue of the biophysical mechanisms that lie at the basis of the method is explored and some hypotheses are proposed. Besides presenting the state-ofthe-art about this novel photobiostimulation therapy, the present paper aims to open up an interdisciplinary discussion and stimulate new research on this subject. © Springer-Verlag London Ltd 2010. Source

Ferraro L.,University of Ferrara | Beggiato S.,IRET Foundation | Beggiato S.,University of Ferrara | Borroto-Escuela D.O.,Karolinska Institutet | And 10 more authors.
Current Protein and Peptide Science | Year: 2014

The tridecapeptide neurotensin (NT) acts as neurotransmitter in the central nervous system and in the periphery. NT and NT receptors are largely localized in dopamine (DA)-enriched regions of the mammalian brain. Accordingly, numerous studies indicate the presence of close functional interactions between DA neurons and the peptide. Among others mechanisms, it has been suggested that NT could modulate nigrostriatal, mesolimbic and meso-cortical DA transmission through an antagonistic receptor-receptor interaction between the NT receptor subtype 1 (NTS1) and the dopamine D2 receptor (D2R). In particular, it was originally demonstrated that the peptide reduces the D2R agonist affinity in striatal sections and in striatal membrane preparations. These effects could be a consequence of the direct allosteric NTS1/D2 receptor interactions leading to a decrease in the DA agonist affinity at the D2 receptor. Several neurochemical, biochemical and co-immunoprecipitation data have successively reinforced the indication of the presence of direct NTS1-D2 receptor interactions in the mammalian brain. The present mini-review attempts to provide a summary of current knowledge, mainly emerging from our microdialysis studies, supporting the presence of a NTS1/D2 receptor heteromer in the brain. The pre and post-synaptic mechanisms underlying the involvement of this heteromer in the striatopallidal GABA and mesocorticolimbic DA neurotransmission are discussed especially for their relevance in Parkinson’s disease and schizophrenia, respectively. © 2014 Bentham Science Publishers Source

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