Decreased γ-aminobutyric acid levels in the parietal region of patients with Alzheimer's disease

Bai, Xi; Edden, Richard A.E.; Gao, Fei; Wang, Guangbin; Wu, Lijian; Zhao, Bin; Wang, Minzhong; Chan, Queenie; Chen, Weibo; Barker, Peter B.

doi:10.1002/jmri.24665

Cited by 94 publications

(69 citation statements)

References 37 publications

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“…Therefore, further study including patients with severe major depression will be performed to evaluate this correlation. Thirdly, similar to our previous study, [37] the voxel volume was relatively large (3 × 3 × 3 cm 3 ; 3 × 3 × 2 cm 3 ) due to the low intensity of the GABA+ signal. Examination of other brain regions will be obligatory to determine whether GABA abnormalities are specific to ACC/mPFC or more broadly distributed throughout the brain.…”

Section: Discussionsupporting

confidence: 85%

“…Quantification was performed using “Gannet” (GABA-MRS Analysis Tool) in Matlab 2010b (Mathworks) with Gaussian curve-fitting to the GABA+ peaks. [36,37] Exponential line broadening of 3 Hz was applied. Gannet provides the standard deviation (SD) of the fitting residues divided by the amplitude of the fitted peaks, generating the overall fitting error which reflects the quality of the data.…”

Section: Methodsmentioning

confidence: 99%

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GABA+ levels in postmenopausal women with mild-to-moderate depression

et al. 2016

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Background:It is increasingly being recognized that alterations of the GABAergic system are implicated in the pathophysiology of depression. This study aimed to explore in vivo gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and posterior-cingulate cortex (PCC) of postmenopausal women with depression using magnetic resonance spectroscopy (1H-MRS).Methods:Nineteen postmenopausal women with depression and thirteen healthy controls were enrolled in the study. All subjects underwent 1H-MRS of the ACC/mPFC and PCC using the “MEGA Point Resolved Spectroscopy Sequence” (MEGA-PRESS) technique. The severity of depression was assessed by 17-item Hamilton Depression Scale (HAMD). Quantification of MRS data was performed using Gannet program. Differences of GABA+ levels from patients and controls were tested using one-way analysis of variance. Spearman correlation coefficients were used to evaluate the linear associations between GABA+ levels and HAMD scores, as well as estrogen levels.Results:Significantly lower GABA+ levels were detected in the ACC/mPFC of postmenopausal women with depression compared to healthy controls (P = 0.002). No significant correlations were found between 17-HAMD/14-HAMA and GABA+ levels, either in ACC/mPFC (P = 0.486; r = 0.170/P = 0.814; r = −0.058) or PCC (P = 0.887; r = 0.035/ P = 0.987; r = −0.004) in the patients; there is also no significant correlation between GABA+ levels and estrogen levels in patients group (ACC/mPFC: P = 0.629, r = −0.018; PCC: P = 0.861, r = 0.043).Conclusion:Significantly lower GABA+ levels were found in the ACC/mPFC of postmenopausal women with depression, suggesting that the dysfunction of the GABAergic system may also be involved in the pathogenesis of depression in postmenopausal women.

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

GABA+ levels in postmenopausal women with mild-to-moderate depression

et al. 2016

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“…Although GABA loss has been variably demonstrated in AD, disruption and significantly reduced GABA transmission are widely observed in AD patients. [52][53][54] We also observed remarkable reduction of 5-HIAA and HVA, the metabolites of 5-HT and DA in dialysates of the htau-expressing mice (data not shown). The hippocampus CA3 has enriched GABAergic inputs and outputs, whereas the serotoninergic and dopaminergic neurons are scarcely seen.…”

Section: Discussionmentioning

confidence: 74%

Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

Wang

Tan

et al. 2017

Molecular Therapy

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Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular g-aminobutyric acid (GABA) level with inhibition of g oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3 0 UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and overexpressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies.

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“…For example, GABAergic transmission deficits have been previously linked to AD (Bai et al, 2014;Iwakiri et al, 2009;Wilcock et al, 1982). Specific subpopulations of inhibitory GABAergic interneurons can be distinguished by their immunoreactivity towards the calcium-binding proteins (CaBPs): calbindin-D28K (CB), calretinin (CR) and parvalbumin (PV), although CR and CB Experimental Gerontology 69 (2015) [176][177][178][179][180][181][182][183][184][185][186][187][188] are also found in some subsets of non-GABAergic neurons (Fujise et al, 1997;Jinno and Kosaka, 2002, 2010.…”

Section: Introductionmentioning

confidence: 94%