Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease

Horgusluoglu‐Moloch, Emrin; Nho, Kwangsik; Risacher, Shannon L.; Kim, Sungeun; Foroud, Tatiana; Shaw, Leslie M.; Trojanowski, John Q.; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford R.; Lovestone, Simon; Simmons, Andrew; Weiner, Michael W.; Saykin, Andrew J.

doi:10.1016/j.neurobiolaging.2017.08.010

Cited by 71 publications

(49 citation statements)

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“…57 Indeed, a gene-based association analysis identified adenosine A 2A R gene ADORA2A as significantly associated with a larger hippocampal volume and better memory. 58 Additionally, because DG new neurons contribute to the growth of the DG tissue through time, 59 the mentioned results reinforce a role of A 2A R in promoting adult neurogenesis. More recently, intraperitoneal administration of an A 2A R selective agonist in rats was shown to be protective against adverse effects on adult neurogenesis, preventing the reduction in Ki67 and doublecortinpositive cells, and also spatial memory impairment as a consequence of exposure to noise-induced hearing loss.…”

Section: Adenosine Receptors In Postnatal Neurogenesismentioning

confidence: 75%

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

Mateus

Ribeiro

Alonso-Gomes

et al. 2019

Journal of Caffeine and Adenosine Research

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The processes of neural genesis, namely neurogenesis, astrogliogenesis, and oligodendrogenesis, that is, the formation of new neurons, astrocytes, and oligodendrocytes start with embryonic development. Of importance, it continues throughout adulthood, not only in the neurogenic niches where neural stem cells (NSCs) are present, but also from glial precursor cells in the brain parenchyma. Therefore, NSCs can be considered a potential therapeutic option in conditions of neural loss and tissue degeneration, as in neurodegenerative diseases. Specifically, stem cell therapy represents a personalized, localized, and probably fruitful alternative in patient care, and is the subject of ongoing research. Nevertheless, many mechanisms of this regenerative therapy remain elusive: if transplantation is required, not only is it necessary to successfully deliver these NSCs to the brain, but they also need to survive, proliferate, and replace the lost neural cells. In line with this, finding ways to manipulate the endogenous sources of NSCs is also very appealing. In particular, adenosine and caffeine (a nonselective antagonist of adenosine receptors), widely studied modulators of neuronal activity, have emerged as potential targets of neurogenesis and oligodendrogenesis. In this article, we review the present concepts on the role of adenosine in embryonic and postnatal neural cell genesis, together with its relevance in the context of brain regeneration.

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Section: Adenosine Receptors In Postnatal Neurogenesismentioning

confidence: 75%

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

Mateus

Ribeiro

Alonso-Gomes

et al. 2019

Journal of Caffeine and Adenosine Research

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“…Disruption of this process can lead to neurodegenerative diseases, including AD. Based on a genetic correlation analysis, adenosine A2AR was significantly correlated with hippocampal volume, adenosine rs9608282 small alleles being associated with a greater hippocampal volume and improved memory . In terms of other receptors, caffeine has a protective effect on the amyloid process by inhibiting the A3R‐mediated internalization of the β‐amyloid precursor .…”

Section: The Role Of Adenosine and Its Receptors In Central Nervous Smentioning

confidence: 99%

Research progress on adenosine in central nervous system diseases

et al. 2019

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As an endogenous neuroprotectant agent, adenosine is extensively distributed and is particularly abundant in the central nervous system (CNS). Under physiological conditions, the concentration of adenosine is low intra‐ and extracellularly, but increases significantly in response to stress. The majority of adenosine functions are receptor‐mediated, and primarily include the A1, A2A, A2B, and A3 receptors (A1R, A2AR, A2BR, and A3R). Adenosine is currently widely used in the treatment of diseases of the CNS and the cardiovascular systems, and the mechanisms are related to the disease types, disease locations, and the adenosine receptors distribution in the CNS. For example, the main infarction sites of cerebral ischemia are cortex and striatum, which have high levels of A1 and A2A receptors. Cerebral ischemia is manifested with A1R decrease and A2AR increase, as well as reduction in the A1R‐mediated inhibitory processes and enhancement of the A2AR‐mediated excitatory process. Adenosine receptor dysfunction is also involved in the pathology of Alzheimer's disease (AD), depression, and epilepsy. Thus, the adenosine receptor balance theory is important for brain disease treatment. The concentration of adenosine can be increased by endogenous or exogenous pathways due to its short half‐life and high inactivation properties. Therefore, we will discuss the function of adenosine and its receptors, adenosine formation, and metabolism, and its role for the treatment of CNS diseases (such as cerebral ischemia, AD, depression, Parkinson's disease, epilepsy, and sleep disorders). This article will provide a scientific basis for the development of novel adenosine derivatives through adenosine structure modification, which will lead to experimental applications.

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“…A single nucleotide polymorphism (SNP) within the GRIN2B gene, which is an N -Methyl- D -Aspartate (NMDA) glutamate receptor and enhances synapse maturation and survival of new-born neurons, is strongly associated with temporal lobe volume in patients with AD and mild cognitive impairment (MCI) [Stein et al, 2010; Kelsch et al, 2012]. Finally, variation within genes strongly related to adult neurogenesis processes in AD such as CHRFAM7A, REST, RELN, BCHE, NCAM1, and ADORA2A have been identified by our colleagues in our laboratory using neuroimaging-genetic methods [Swaminathan et al, 2011, 2012; Ramanan et al, 2012, 2014; Horgusluoglu et al, 2015; Nho et al, 2015]. …”

Section: Modulators Of Adult Neurogenesismentioning

confidence: 99%

Adult neurogenesis and neurodegenerative diseases: A systems biology perspective

Horgusluoglu

Nudelman

Nho

et al. 2016

American J of Med Genetics Pt B

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146

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New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research.

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Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease

Cited by 71 publications

References 59 publications

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

Research progress on adenosine in central nervous system diseases

Adult neurogenesis and neurodegenerative diseases: A systems biology perspective

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