Cognitive impairments associated with alterations in synaptic proteins induced by the genetic loss of adenosine A 2A receptors in mice

Moscoso-Castro, María; López-Cano, Marc; Gracia-Rubio, Irene; Ciruela, Francisco; Valverde, Olga

doi:10.1016/j.neuropharm.2017.08.027

Cited by 28 publications

(13 citation statements)

References 69 publications

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“…We found that A 2A R activation and ENT1 inhibitor could improve neurodegeneration in aging. Our results are complementary to Moscoso-Castro et al, who found that deletion of A 2A R led to deficits in spatial memory and learning as well as decreased neurogenesis [ 41 ]. However, A 2A R activation or inhibition as a benefit for anti-aging is controversial [ 14 , 42 ].…”

Section: Discussionsupporting

confidence: 86%

T1-11, an adenosine derivative, ameliorates aging-related behavioral physiology and senescence markers in aging mice

Hsu

Shiao

Chao

et al. 2020

Aging

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Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effect of N 6 -(4-hydroxybenzyl)adenine riboside (T1-11), an adenosine analog isolated from Gastrodia elata , in a mouse model of aging created by D-galactose (D-gal) and the underlying mechanism, as well as explore the role of adenosine signaling in aging. T1-11 activated A 2A R and suppressed D-gal- and BeSO 4 -induced cellular senescence in vitro . In vivo results in mice revealed that T1-11 abated D-gal-induced reactive oxygen species generation and ameliorated cognitive decline by inducing neurogenesis and lowering D-gal-caused neuron death. T1-11 could be a potent agent for postponing senility and preventing aging-related neuroinflammation and neurodegeneration.

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Section: Discussionsupporting

confidence: 86%

T1-11, an adenosine derivative, ameliorates aging-related behavioral physiology and senescence markers in aging mice

Hsu

Shiao

Chao

et al. 2020

Aging

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“…Animals were killed 30 min after the cocaine‐primed reinstatement session, and PFC and STR were extracted, quickly frozen in dry ice and stored at −80°C until used for western blotting, as previously described (Moscoso‐Castro, López‐Cano, Gracia‐Rubio, Ciruela, & Valverde, ). In addition, PFC and STR were extracted in cocaine‐naïve animals to analyse GluA1 and GluA2 levels at basal conditions (see Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

“…Moscoso-Castro, López-Cano, Gracia-Rubio, Ciruela, & Valverde, 2017). In addition, PFC and STR were extracted in cocaine-naïve animals to analyse GluA1 and GluA2 levels at basal conditions (seeSupporting Information).…”

mentioning

confidence: 99%

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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Background and Purpose Alcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring. Experimental Approach Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement. Key Results The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement. Conclusion and Implications Our findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.

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“…The adenosine hypothesis of schizophrenia [13,14] was recently bolstered by the observation that A 2A R deletion (A 2A R -/-) prompts behaviours that mimic symptoms of psychosis and molecular/anatomical alterations in mice, resembling the relevant phenotype features of the human disorder [23,27,28]. We first validated the A 2A R -/-based animal model of psychotic symptoms by comparing it with the well-established PCP animal model of sensory gating impairment of schizophrenia [19,29,30].…”

Section: Alterations In Sensorimotor Gating In Pcp Treated Animals Anmentioning

confidence: 99%

Decreased striatal adenosine A2A-dopamine D2 receptor heteromerization in schizophrenia

Valle-León

Callado

Aso

et al. 2020

Neuropsychopharmacol.

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According to the adenosine hypothesis of schizophrenia, the classically associated hyperdopaminergic state may be secondary to a loss of function of the adenosinergic system. Such a hypoadenosinergic state might either be due to a reduction of the extracellular levels of adenosine or alterations in the density of adenosine A 2A receptors (A 2A Rs) or their degree of functional heteromerization with dopamine D 2 receptors (D 2 R). In the present study, we provide preclinical and clinical evidences for this latter mechanism. Two animal models for the study of schizophrenia endophenotypes, namely the phencyclidine (PCP) mouse model and the A 2A R knockout mice, were used to establish correlations between behavioral and molecular studies. In addition, a new AlphaLISA-based method was implemented to detect native A 2A R-D 2 R heteromers in mouse and human brain. First, we observed a reduction of prepulse inhibition in A 2A R knockout mice, similar to that observed in the PCP animal model of sensory gating impairment of schizophrenia, as well as a significant upregulation of striatal D 2 R without changes in A 2A R expression in PCP-treated animals. In addition, PCP-treated animals showed a significant reduction of striatal A 2A R-D 2 R heteromers, as demonstrated by the AlphaLISA-based method. A significant and pronounced reduction of A 2A R-D 2 R heteromers was next demonstrated in post-mortem caudate nucleus from schizophrenic subjects, even though both D 2 R and A 2A R were upregulated. Finally, in PCP-treated animals, sub-chronic administration of haloperidol or clozapine counteracted the reduction of striatal A 2A R-D 2 R heteromers. The degree of A 2A R-D 2 R heteromer formation in schizophrenia might constitute a hallmark of the illness which indeed should be further studied to stablish possible correlations with chronic antipsychotic treatments.

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Cognitive impairments associated with alterations in synaptic proteins induced by the genetic loss of adenosine A 2A receptors in mice

Cited by 28 publications

References 69 publications

T1-11, an adenosine derivative, ameliorates aging-related behavioral physiology and senescence markers in aging mice

T1-11, an adenosine derivative, ameliorates aging-related behavioral physiology and senescence markers in aging mice

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Decreased striatal adenosine A2A-dopamine D2 receptor heteromerization in schizophrenia

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