Differential localization of GABAA receptor subunits within the substantia nigra of the human brain: An immunohistochemical study

2007 ◽  
Vol 506 (6) ◽  
pp. 912-929 ◽  
Author(s):  
H.J. Waldvogel ◽  
K. Baer ◽  
W.-P. Gai ◽  
R.T. Gilbert ◽  
M.I. Rees ◽  
...  
2007 ◽  
Vol 502 (6) ◽  
pp. 1012-1029 ◽  
Author(s):  
Henry J. Waldvogel ◽  
Kristin Baer ◽  
Kathryn L. Allen ◽  
Mark I. Rees ◽  
Richard L.M. Faull

2010 ◽  
pp. 73-93 ◽  
Author(s):  
H. J Waldvogel ◽  
K Baer ◽  
R. L. M. Faull

2011 ◽  
Vol 33 (5) ◽  
pp. 868-878 ◽  
Author(s):  
A. Gross ◽  
R. E. Sims ◽  
J. D. Swinny ◽  
W. Sieghart ◽  
J. P. Bolam ◽  
...  

1998 ◽  
Vol 19 (4) ◽  
pp. 205-210 ◽  
Author(s):  
J. Veĺišková ◽  
E. F. Sperber ◽  
S. L. Moshé ◽  
H. Kubová ◽  
L. K. Friedman ◽  
...  

2017 ◽  
Author(s):  
Elizabeth Nacheva ◽  
Katya Mokretar ◽  
Aynur Soenmez ◽  
Alan M Pittman ◽  
Colin Grace ◽  
...  

AbstractPotential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array “waves”, and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance.


2020 ◽  
Author(s):  
Sejal Patel ◽  
Derek Howard ◽  
Leon French

BACKGROUND: Parkinson's disease (PD) causes severe motor and cognitive disabilities that result from the progressive loss of dopamine neurons in the substantia nigra. The rs12456492 variant in the RIT2 gene has been repeatedly associated with increased risk for Parkinson's disease. From a transcriptomic perspective, a meta-analysis found that RIT2 gene expression is correlated with pH in the human brain. OBJECTIVE: To assess pH associations at the RIT2-SYT4 locus. METHODS: Linear models to examine two datasets that assayed rs12456492, gene expression, and pH in the postmortem human brain. RESULTS: Using the BrainEAC dataset, we replicate the positive correlation between RIT2 gene expression and pH in the human brain. Furthermore, we found that the relationship between expression and pH is influenced by rs12456492. When tested across ten brain regions, this interaction is specifically found in the substantia nigra. A similar association was found for the co-localized SYT4 gene. In addition, SYT4 associations are stronger in a combined model with both genes, and the SYT4 interaction appears to be specific to males. In the GTEx dataset, the pH associations involving rs12456492 and expression of either SYT4 and RIT2 was not seen. This null finding may be due to the short postmortem intervals (PMI) of the GTEx tissue samples. In the BrainEAC data, we tested the effect of PMI and only observed the interactions in the longer PMI samples. CONCLUSIONS: These previously unknown associations suggest novel mechanistic roles for rs12456492, RIT2, and SYT4 in the regulation of pH in the substantia nigra.


2013 ◽  
Vol 16 (6) ◽  
pp. 1361-1371 ◽  
Author(s):  
Caroline Nothdurfter ◽  
Sascha Tanasic ◽  
Barbara Di Benedetto ◽  
Manfred Uhr ◽  
Eva-Maria Wagner ◽  
...  

Abstract Lipid rafts have been shown to play an important role for G-protein mediated signal transduction and the function of ligand-gated ion channels including their modulation by psychopharmacological compounds. In this study, we investigated the functional significance of the membrane distribution of NMDA and GABAA receptor subunits in relation to the accumulation of the tricyclic antidepressant desipramine (DMI) and the benzodiazepine diazepam (Diaz). In the presence of Triton X-100, which allowed proper separation of the lipid raft marker proteins caveolin-1 and flotillin-1 from the transferrin receptor, all receptor subunits were shifted to the non-raft fractions. In contrast, under detergent-free conditions, NMDA and GABAA receptor subunits were detected both in raft and non-raft fractions. Diaz was enriched in non-raft fractions without Triton X-100 in contrast to DMI, which preferentially accumulated in lipid rafts. Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA. These results support the hypothesis that the interaction of benzodiazepines with the GABAA receptor likely occurs outside of lipid rafts while the antidepressant DMI acts on ionotropic receptors both within and outside these membrane microdomains.


Neuroscience ◽  
1987 ◽  
Vol 22 (3) ◽  
pp. 781-800 ◽  
Author(s):  
C. Bouras ◽  
P.J. Magistretti ◽  
J.H. Morrison ◽  
J. Constantinidis

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