Glial cell number and neuron/glial cell ratios in postmortem brains of bipolar individuals

Brauch, Rebecca; El-Masri, M. Adrian; Parker, Joseph C.; El‐Mallakh, Rif S.

doi:10.1016/j.jad.2005.08.015

Cited by 45 publications

(30 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Age-and gender-modulated regional differences in the brain nucleoside system [11, 16-22] suggest (i) the existence of specific nucleoside pools in different brain areas, (ii) significant spatial differences in the nucleoside metabolic (anabolic and catabolic) network and signaling mechanisms induced by Ado and non-Ado nucleosides (i.e., Urd and Guo), (iii) fine and highly regulated modulation of different physiological processes in different human brain areas by nucleosides, (iv) the effect of nucleoside microenvironment on aging, which may be modulated by gender and (v) pathological consequences of changes in the nucleoside system, which may be related to the development of different CNS diseases, such as major depression, bipolar disorders, schizophrenia, Huntington's disease, Parkinson's disease and Alzheimer's disease as well as frontotemporal dementia [7,50,[177][178][179][180][181][182][183][184][185][186].…”

Section: Regional Differences and Correlations In The Nucleoside Systmentioning

confidence: 99%

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Kovács

Dobolyi

Kékesi

et al. 2013

CMC

View full text Add to dashboard Cite

Elements of the nucleoside system (nucleoside levels, 5'-nucleotidases (5'NTs) and other nucleoside metabolic enzymes, nucleoside transporters and nucleoside receptors) are unevenly distributed in the brain, suggesting that nucleosides have region-specific functions in the human brain. Indeed, adenosine (Ado) and non-Ado nucleosides, such as guanosine (Guo), inosine (Ino) and uridine (Urd), modulate both physiological and pathophysiological processes in the brain, such as sleep, pain, memory, depression, schizophrenia, epilepsy, Huntington's disease, Alzheimer's disease and Parkinson's disease. Interactions have been demonstrated in the nucleoside system between nucleoside levels and the activities of nucleoside metabolic enzymes, nucleoside transporters and Ado receptors in the human brain. Alterations in the nucleoside system may induce pathological changes, resulting in central nervous system (CNS) diseases. Moreover, several CNS diseases such as epilepsy may be treated by modulation of the nucleoside system, which is best achieved by modulating 5'NTs, as 5'NTs exhibit numerous functions in the CNS, including intracellular and extracellular formation of nucleosides, termination of nucleoside triphosphate signaling, cell adhesion, synaptogenesis and cell proliferation. Thus, modulation of 5'NT activity may be a promising new therapeutic tool for treating several CNS diseases. The present article describes the regionally different activities of the nucleoside system, demonstrates the associations between these activities and 5'NT activity and discusses the therapeutic implications of these associations.

show abstract

Section: Regional Differences and Correlations In The Nucleoside Systmentioning

confidence: 99%

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Kovács

Dobolyi

Kékesi

et al. 2013

CMC

View full text Add to dashboard Cite

show abstract

“…However, the correlation between the neuron-glia ratio and nucleoside levels in the human brain is weak (Kovács et al 2010a ) . Importantly, the neuron-glia ratio is changed in some brain areas implicated in the development of major depressive and bipolar disorders, schizophrenia, Huntington's and Alzheimer's disease, and frontotemporal dementia (Bowley et al 2002 ;Brauch et al 2006 ;Harper et al 2008 ;Öngür et al 1998 ;Roos et al 1985 ) . Table 29.1 shows that altered nucleoside metabolic enzyme activity may result in an uneven distribution of nucleosides and their metabolites in the human brain (Kovács et al 2010a (Table 29.1 ).…”

Section: Distribution Of Nucleoside Metabolic Enzymesmentioning

confidence: 99%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

View full text Add to dashboard Cite

Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

show abstract

“…The underlying causes of elevated levels of S100B in neurological and psychiatric disorders are unknown. It may result from identified glial cell abnormalities [Benes et al, 1991;Cotter et al, 2001;Webster et al, 2005;Brauch et al, 2006] or possibly an increased secretion from glial cells as part of a neuroprotective response, as supported by a preliminary study of first-onset schizophrenic patients [Steiner et al, 2006]. In patients with major depression or SZ, S100B protein levels positively correlate with symptom scores/severity and tend to normalize in treatment responders yet remain elevated in nonresponders [Schroeter et al, 2002;Arolt et al, 2003;Rothermundt et al, 2004c].…”

mentioning

confidence: 92%

Functional assessment of a promoter polymorphism in S100B, a putative risk variant for bipolar disorder

Dağdan¹,

Morris²,

Campbell³

et al. 2011

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Calcium-binding protein S100B has been implicated in the pathology of bipolar affective disorder (BPAD) and schizophrenia (SZ). S100B protein levels are elevated in serum of patients with both disorders compared to controls. We previously reported genetic association of a SNP in the promoter of S100B, rs3788266, with a psychotic form of BPAD. To test for genotypic effects of rs3788266 in vivo, S100B serum protein levels were measured in 350 Irish and German subjects of known S100B genotype. The functional effect of rs3788266 on S100B promoter activity was studied using the luciferase reporter system in U373MG glioblastoma and SH-SY5Y neuroblastoma cell lines. Allelic effects of rs3788266 on protein complex formation at the S100B promoter were investigated by an electrophoretic mobility shift assay. Higher mean serum S100B levels were associated with the risk G allele of rs3788266 in BPAD cases (P = 0.0001), unaffected relatives of BPAD cases (P< 0.0001) and unrelated controls (P < 0.0001). Consistent with the in vivo findings, luciferase gene expression was significantly increased in the presence of the G allele compared to the A allele in SH-SY5Y (P = <0.0001), and in U373MG (P = <0.0008) cell lines. The binding affinity of both SH-SY5Y and U373MG protein complexes for the S100B promoter was significantly stronger in the presence of G allele compared to the A allele promoter fragments. These data support rs3788266 as a functional promoter variant in the S100B gene where the presence of the G allele promotes increased gene expression and is associated with increased serum levels of the protein.

show abstract

Glial cell number and neuron/glial cell ratios in postmortem brains of bipolar individuals

Cited by 45 publications

References 13 publications

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Functional assessment of a promoter polymorphism in S100B, a putative risk variant for bipolar disorder

Contact Info

Product

Resources

About

Glial cell number and neuron/glial cell ratios in postmortem brains of bipolar individuals

Cited by 45 publications

References 13 publications

5&#39;-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

5&#39;-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Functional assessment of a promoter polymorphism in S100B, a putative risk variant for bipolar disorder

Contact Info

Product

Resources

About

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications