Adenosine A2A receptor antagonism increases nNOS-immunoreactive neurons in the striatum of Huntington transgenic mice

Cipriani, Sara; Bizzoco, Elisa; Gianfriddo, Marco; Melani, Alessia; Vannucchi, Maria Giuliana; Pedata, Felicita

doi:10.1016/j.expneurol.2008.05.015

Cited by 23 publications

(10 citation statements)

References 72 publications

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“…However, L-NAME (non selective NOS inhibitor) pretreatment with a sub-effective dose of lycopene potentiated the protective effect, suggesting that the protective effect of lycopene might involve a nitric oxide mechanism. Role of nitric oxide has also been suggested in the pathophysiology of Huntington's disease (Cipriani et al 2008) and 3-NP-induced neurotoxicity (Deshpande et al 2006). Our study results also strengthened the hypothesis of nitrosative stress against 3-NP-induced neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

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Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity

2009

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Section: Discussionmentioning

confidence: 99%

“…A role for nitric oxide has also been suggested in the pathophysiology of Huntington's disease (Cipriani et al 2008) and 3-NP-induced neurotoxicity (Deshpande et al 2006). Nitric oxide significantly modulates these pathological conditions (Deshpande et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity

2009

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“…The role of nitric oxide (NO) has also been well suggested in the pathophysiolgy of HD (Cipriani et al, 2008) and 3-NP induced neurotoxicity (Deshpande et al, 2006). NO is a free radical, synthesized from L-arginine, involved in a wide range of physiological (Knott and Bossy-Wetzel, 2008) and pathological conditions, including HD.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acid-induced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease

Kumar

Kalonia²,

Kumar³

2010

Behavioural Pharmacology

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Huntington's disease (HD), a basal ganglia disorder, is characterized not only by a spectrum of motor deficits, but also by emotional, cognitive and psychiatric manifestations. Cognitive impairment is one of the serious manifestations of this disease in the later stage of life. Although there is currently no cure for HD, there has been a surge of clinical trials involving patients with HD over the past 5 years. However, cognitive measures have generally been lacking from these trials. The beneficial effect of antidepressants in HD has been suggested in recent clinical trials. However, their mechanism of action is still not clear. Therefore, this study was designed to elucidate and compare the mechanistic role of different classes of antidepressants (sertraline, venlafaxine, imipramine and trazodone) against 3-nitropropionic acid (3-NP)-induced cognitive impairment, oxidative stress (glutathione) and mitochondrial dysfunction in rat hippocampus. Systemic treatment with 3-NP (10 mg/kg for 14 days) significantly impaired memory performance (both in the Morris water maze and elevated plus maze escape retention test), oxidative defence (glutathione redox status) and mitochondrial enzyme complex activities in rat hippocampus. Sertraline, venlafaxine, imipramine and trazodone treatments significantly improved performance in both cognitive tasks and glutathione redox status, and restored mitochondrial enzyme complex activities, as compared with the 3-NP treated group. L-arginine (50 mg/kg) pretreatment for 14 days together with a subeffective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) or trazodone (10 mg/kg) partially attenuated their protective effects. Further, G-nitro-L-Arginine-Methyl Ester (10 mg/kg) pretreatment together with subeffective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) significantly enhanced their efficacy. The results of this study suggest that nitric oxide modulation is involved in their protective effect of antidepressants against 3-NP induced cognitive dysfunction in rats.

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“…Studies showed that the administration of the A 2A R antagonist SCH58261 in R6/2 mice reduced glutamate and adenosine outflow, normalized the alteration in emotional response, and reduced NMDAinduced toxicity, 226,227 but had no effect on locomotor capability. 226,228 Genetic and pharmacological inactivation of A 2A R reduced working memory deficits in R6/2 mice, 229 and the combined blockade of D 1 R and A 2A R improved cognitive dysfunction in a different transgenic HD mouse model (R6/1). 230 Taken together, these results suggest that A 2A R blockade may be able to reverse the cognitive impairment that develops in these HD mice.…”

Section: Alterations In Striatal Adenosine Tone In Hdmentioning

confidence: 98%

The Role of Adenosine Tone and Adenosine Receptors in Huntington's Disease

Blum

Chern

Domenici

et al. 2018

Journal of Caffeine and Adenosine Research

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Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a mutation in the IT15 gene that encodes for the huntingtin protein. Mutated hungtingtin, although widely expressed in the brain, predominantly affects striato-pallidal neurons, particularly enriched with adenosine A 2A receptors (A 2A R), suggesting a possible involvement of adenosine and A 2A R is the pathogenesis of HD. In fact, polymorphic variation in the ADORA2A gene influences the age at onset in HD, and A 2A R dynamics is altered by mutated huntingtin. Basal levels of adenosine and adenosine receptors are involved in many processes critical for neuronal function and homeostasis, including modulation of synaptic activity and excitotoxicity, the control of neurotrophin levels and functions, and the regulation of protein degradation mechanisms. In the present review, we critically analyze the current literature involving the effect of altered adenosine tone and adenosine receptors in HD and discuss why therapeutics that modulate the adenosine system may represent a novel approach for the treatment of HD.Keywords: Huntington's disease, adenosine, adenosine receptors, equilibrative nucleoside transporter, animal models Pathogenic Mechanisms of Huntington's DiseaseOverview H untington's disease (HD) is an inherited neurodegenerative disorder that is caused by a single, autosomal dominant gene mutation. HD generally affects young adults and is characterized by involuntary, abnormal movements and postures (chorea, dyskinesia, dystonia), psychiatric disturbances, and cognitive alterations.1,2 It is estimated that 1 in 10,000 people have HD and this disorder is fatal within 15-20 years after the onset of symptoms. Multiple brain regions, including several cortical and subcortical regions (cerebral cortex, layers III, V, and VI; pallidum, sub-thalamic nucleus, cerebellum), show signs of neurodegeneration, but the most pronounced neuronal loss is present in the caudate nucleus and the putamen of the striatum.3 Within the striatum, the striato-pallidal, medium spiny neurons (MSN) that express enkephalin, dopamine D 2 receptors (D 2 R) and adenosine A 2A receptors (A 2A R), 4,5 appear to be the most vulnerable.6,7

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Adenosine A2A receptor antagonism increases nNOS-immunoreactive neurons in the striatum of Huntington transgenic mice

Cited by 23 publications

References 72 publications

Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity

Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity

Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acid-induced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease

The Role of Adenosine Tone and Adenosine Receptors in Huntington's Disease

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