Reduced density of adenosine A1 receptors and preserved coupling of adenosine A1 receptors to G proteins in alzheimer hippocampus: A quantitative autoradiographic study

Ułas, J.; Brunner, L.C.; Nguyen, Long V.; Cotman, Carl W.

doi:10.1016/0306-4522(93)90533-l

Cited by 79 publications

(38 citation statements)

References 63 publications

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“…This decreased density of A 1 Rs is in general agreement with the development of tolerance in relation to the anti-convulsive effects of A 1 receptor agonists [198,199] that is accompanied by a reduced potency of A 1 R agonists [120]. In other chronic neurodegenerative conditions, such as Alzheimer's disease, the density of A 1 Rs is also reduced ( [206,397,398]; but see [207]). Likewise, several studies showed that short periods of brain ischemia, which also trigger a robust increase in the extracellular levels of adenosine ( [121]; reviewed in [172]), produce a long-lasting decrease in the density of A 1 Rs in several brain regions (e.g., [200Y202]).…”

Section: Modification Of Adenosine Metabolism On Stressful Conditionssupporting

confidence: 58%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

484

432

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Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A

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Section: Modification Of Adenosine Metabolism On Stressful Conditionssupporting

confidence: 58%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

484

432

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“…Now, we extended these findings to neurons, the brain cells where the predominant expression of adenosine A 1 receptors occurs (Onodera and Kogure, 1988;Ulas et al, 1993;Swanson et al, 1995) and where adenosine acts to refrain excitatory transmission and to protect from uncoordinated firing (Dragunow, 1988;Dunwiddie and Masino, 2001). Indeed, the neuronal adenosine A 1 receptor represents a major endogenous neuroprotective system and it has long been suggested that the upregulation of A 1 receptor expression increases its IL-6, neuronal adenosine A 1 receptor and brain function K Biber et al neuroprotective capacities (for review, see Rudolphi and Schubert, 1996;Dunwiddie and Masino, 2001).…”

Section: Discussionmentioning

confidence: 80%

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Biber

Pinto-Duarte

Wittendorp

et al. 2007

Neuropsychopharmacol

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The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A 1 receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A 1 receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.

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“…Activation of A 1 receptors results in a reduction of synaptic glutamate release (Prestwich et al 1987), thereby regulating neuronal activity, synaptic plasticity and learning (reviewed by Fredholm et al 2005a, b;Stone et al 2009). The importance of A 1 receptors for synaptic transmission is underlined by the fact that a significant decline of A 1 receptor density was numerously demonstrated in brains of patients suffering from Alzheimer's disease (AD) (Jansen et al 1990;Kalaria et al 1990;Jaarsma et al 1991;Ikeda et al 1993;Ułas et al 1993;Fukumitsu et al, 2008). An increasing body of evidence also implies a role for the reelin pathway in AD.…”

Section: Implications For Reelin Function In Neurodegenerative Diseasesmentioning

confidence: 97%

Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions

et al. 2011

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Mapping of multiple receptors of neurotransmitters provides insight into the spatial distribution of neurotransmission-relevant molecules in the cerebral cortex. During development, lack of reelin leads to impaired migration, disturbed lamination of the hippocampus and inverted neocortical layering. In the adult, reelin may regulate synaptic plasticity by modulating neurotransmitter receptor function. Using quantitative in vitro receptor autoradiography, different receptors, in particular, the binding site densities and laminar distribution of various glutamate, GABA, muscarinic and nicotinic acetylcholine, serotonin, dopamine and adenosine receptors, were analyzed in cortical and subcortical structures of reeler and wild-type brains. Differential changes in the laminar distribution, maximum binding capacity (B (max)) and regional density of neurotransmitter receptors were found in the reeler brain. A decrease of whole brain B (max) was found for adenosine A(1) and GABA(A) receptors. In the forebrain, several binding sites were differentially up- or down-regulated (kainate, A(1), benzodiazepine, 5-HT(1), M(2), α(1) and α(2)). In the hippocampus, a significant decrease of GABA(B), 5-HT(1) and A'₁ receptors were observed. The density of M(2) receptors increased, while other receptors remained unchanged. In the neocortex, some receptors demonstrated an obviously inverted laminar distribution (AMPA, kainate, NMDA, GABA(B), 5-HT(1), M(1), M(3), nAch), while the distribution of others (A(1), GABA(A), benzodiazepine, 5-HT(2), muscarinic M(2), adrenergic α(1), α(2)) seemed to be less affected. Thus, the laminar receptor distribution is modulated by the developmental impairment and suggests and reflects partially the laminar inversion in reeler mice.

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Reduced density of adenosine A1 receptors and preserved coupling of adenosine A1 receptors to G proteins in alzheimer hippocampus: A quantitative autoradiographic study

Cited by 79 publications

References 63 publications

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions

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