Considering the heterogeneity of pathological changes occurring in Alzheimer's disease (AD), acknowledge as progressive multifactorial neurodegenerative disorder, a therapeutic approach aimed both to neuroprotection and to neuroinflammation reduction may prove effective. Palmitoylethanolamide (PEA), abundant in the central nervous system and produced by neurons and glial cells, has attracted attention for its anti-inflammatory/neuroprotective properties observed in AD animal models. In the present study, we evaluated the protective role of PEA pretreatment (0.1 μM, 1 hour), against amyloid-β42 (Aβ42) (0.5 μM; 24 hours) 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. Aβ42 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. 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. Furthermore, Aβ42 is able to alter the morphology and to decrease the number of cells in cultured cortical neurons and astrocytes from non-Tg mice, but not in those from 3xTg-AD mice. These alterations in neurons and in astrocytes are completely counteracted by the pretreatment with PEA. By itself, PEA did not affect morphology, cell viability and glutamate levels in cultured cortical neuron and astrocytes from non-Tg or 3xTg-AD mice. In 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.

Considerando l’eterogeneità dei cambiamenti patologici che avvengono nella malattia di Alzheimer (AD), disordine neurodegenerativo e multifattoriale, un approccio terapeutico potrebbe dimostrarsi efficace se mirato sia alla neuroprotezione che alla riduzione della neuroinfiammazione . La Palmitoiletanolamide (PEA), abbondante nel sistema nervoso centrale e prodotta sia dai neuroni che dalle cellule gliali, ha attirato particolare attenzione per le sue proprietà antinfiammatorie e neuroprotettive osservate nei modelli animali di AD. In questo studio è stato valutato il ruolo protettivo di un pretrattamento con PEA (0.1 μM, 1 ora) nella tossicità indotta dall’amilode-β42 (Aβ42) (0.5 μΜ, 24 ore), in termini morfologici, di vitalità cellulare e di trasmissione glutammatergica in colture primarie corticali di neuroni e astrociti ottenute da topi transgenici, con la tripla mutazione per la malattia di Alzheimer (3xTg-AD), e da topi non mutati, di controllo (non-Tg). Aβ42 altera la vitalità cellulare nelle colture corticali di neuroni e astrociti non-Tg, ma non in quelle 3xTg-AD. Questo effetto viene a mancare in caso di pretrattamento con PEA. I livelli basali di glutammato in neuroni e astrociti 3xTg-AD sono inferiori a quelli osservati nelle colture di controllo non-Tg. L’esposizione ad Aβ42 delle colture corticali neuronali e astrocitarie non-Tg provoca rispettivamente una riduzione e un aumento dei livelli di glutammato. Tali alterazioni vengono a mancare in caso di pretrattamento con PEA. Inoltre, Aβ42 è in grado di alterare la morfologia e il numero delle cellule nelle colture corticali di neuroni e astrociti non-Tg, ma non in 3xTg-AD. Queste modificazioni non si verificano in caso di pretrattamento con PEA. Di per sé, invece, PEA non influenza la morfologia, o la vitalità cellulare e nemmeno i livelli di glutammato nelle colture neuronali e astrocitarie ottenute sia da topi non-Tg che da quelli 3xTg-AD. In conclusione, l’esposizione ad Aβ42 induce effetti tossici nelle colture corticali di neuroni e astrociti non-Tg, ma non in quelle 3xTg-AD. PEA esercita molteplici effetti nella tossicità indotta da Aβ42 nelle colture non-Tg ma non in quelle 3xTg-AD. In particolare, PEA sembra avere proprietà protettive nelle colture non-Tg ma non in quelle 3xTg-AD, sovraesprimenti Aβ.

Differential effects of palmitoylethanolamide against amyloid-β induced toxicity in cortical neuronal and astrocytic primary cultures from wild-type and 3xTG-AD mice.

BORELLI, ANDREA CELESTE
2016

Abstract

Considering the heterogeneity of pathological changes occurring in Alzheimer's disease (AD), acknowledge as progressive multifactorial neurodegenerative disorder, a therapeutic approach aimed both to neuroprotection and to neuroinflammation reduction may prove effective. Palmitoylethanolamide (PEA), abundant in the central nervous system and produced by neurons and glial cells, has attracted attention for its anti-inflammatory/neuroprotective properties observed in AD animal models. In the present study, we evaluated the protective role of PEA pretreatment (0.1 μM, 1 hour), against amyloid-β42 (Aβ42) (0.5 μM; 24 hours) 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. Aβ42 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. 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. Furthermore, Aβ42 is able to alter the morphology and to decrease the number of cells in cultured cortical neurons and astrocytes from non-Tg mice, but not in those from 3xTg-AD mice. These alterations in neurons and in astrocytes are completely counteracted by the pretreatment with PEA. By itself, PEA did not affect morphology, cell viability and glutamate levels in cultured cortical neuron and astrocytes from non-Tg or 3xTg-AD mice. In 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.
TOMASINI, Maria Cristina
CUNEO, Antonio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2403493
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