nach oben

Erschienen in:

06.10.2017 | Magnetic Resonance

Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

verfasst von: Guanmei Cao, Richard A. E. Edden, Fei Gao, Hao Li, Tao Gong, Weibo Chen, Xiaohui Liu, Guangbin Wang, Bin Zhao

Erschienen in: European Radiology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Objectives

To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS.

Methods

Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the ‘MEGAPoint Resolved Spectroscopy Sequence’ (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment.

Results

In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05).

Conclusions

This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS.

Key points

• GABA levels may decrease in patients with RRMS.

• Lower GABA levels correlated with worse cognitive performance in patients with RRMS.

• Dysfunctional GABAergic neurotransmission may have a role in cognitive impairment in RRMS.

DeLuca GC, Yates RL, Beale H, Morrow SA (2015) Cognitive impairment in multiple sclerosis: clinical, radiologic and pathologic insights. Brain Pathol 25:79–98CrossRefPubMed

Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7:1139–1151CrossRefPubMed

Duncan NW, Wiebking C, Northoff G (2014) Associations of regional GABA and glutamate with intrinsic and extrinsic neural activity in humans—a review of multimodal imaging studies. Neurosci Biobehav Rev 47:36–52CrossRefPubMed

Koenig KA, Sakaie KE, Lowe MJ et al (2014) Hippocampal volume is related to cognitive decline and fornicial diffusion measures in multiple sclerosis. Magn Reson Imaging 32:354–358CrossRefPubMed

Van Schependom J, Gielen J, Laton J et al (2017) The effect of morphological and microstructural integrity of the corpus callosum on cognition, fatigue and depression in mildly disabled MS patients. Magn Reson Imaging 40:109–114CrossRefPubMed

Bartos M, Vida I, Jonas P (2007) Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci 8:45–56CrossRefPubMed

Sumner P, Edden RA, Bompas A, Evans CJ, Singh KD (2010) More GABA, less distraction: a neurochemical predictor of motor decision speed. Nat Neurosci 13:825–827CrossRefPubMed

Boy F, Evans CJ, Edden RA et al (2011) Dorsolateral prefrontal gamma-aminobutyric acid in men predicts individual differences in rash impulsivity. Biol Psychiatry 70:866–872CrossRefPubMedPubMedCentral

Harris AD, Saleh MG, Edden RA (2017) Edited 1 H magnetic resonance spectroscopy in vivo: methods and metabolites. Magn Reson Med 77:1377–1389CrossRefPubMed

10.

Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R (1998) Simultaneous in vivo spectral editing and water suppression. NMR Biomed 11:266–272CrossRefPubMed

11.

Edden RA, Crocetti D, Zhu H, Gilbert DL, Mostofsky SH (2012) Reduced GABA concentration in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 69:750–753CrossRefPubMedPubMedCentral

12.

Voleti B, Navarria A, Liu RJ et al (2013) Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses. Biol Psychiatry 74:742–749CrossRefPubMed

13.

Milak MS, Proper CJ, Mulhern ST et al (2016) A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder. Mol Psychiatry 21:320–327CrossRefPubMed

14.

Gao F, Edden RA, Li M et al (2013) Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels. NeuroImage 78:75–82CrossRefPubMedPubMedCentral

15.

Stagg CJ (2014) Magnetic Resonance Spectroscopy as a tool to study the role of GABA in motor-cortical plasticity. NeuroImage 86:19–27CrossRefPubMed

16.

Greenhouse I, King M, Noah S, Maddock RJ, Ivry RB (2017) Individual differences in resting corticospinal excitability are correlated with reaction time and GABA content in motor cortex. J Neurosci 37:2686–2696CrossRefPubMedPubMedCentral

17.

Cawley N, Solanky BS, Muhlert N et al (2015) Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis. Brain 138:2584–2595CrossRefPubMedPubMedCentral

18.

Bhattacharyya PK, Phillips MD, Stone LA, Bermel RA, Lowe MJ (2013) Sensorimotor cortex gamma-aminobutyric acid concentration correlates with impaired performance in patients with MS. AJNR Am J Neuroradiol 34:1733–1739CrossRefPubMed

19.

Hu Y, Chen X, Gu H, Yang Y (2013) Resting-state glutamate and GABA concentrations predict task-induced deactivation in the default mode network. J Neurosci 33:18566–18573CrossRefPubMedPubMedCentral

20.

Leech R, Sharp DJ (2014) The role of the posterior cingulate cortex in cognition and disease. Brain 137:12–32CrossRefPubMed

21.

Mainero C, Caramia F, Pozzilli C et al (2004) fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. NeuroImage 21:858–867CrossRefPubMed

22.

Louapre C, Perlbarg V, Garcia-Lorenzo D et al (2014) Brain networks disconnection in early multiple sclerosis cognitive deficits: an anatomofunctional study. Hum Brain Mapp 35:4706–4717CrossRefPubMed

23.

Rocca MA, Longoni G, Pagani E et al (2015) In vivo evidence of hippocampal dentate gyrus expansion in multiple sclerosis. Hum Brain Mapp 36:4702–4713CrossRefPubMed

24.

Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefPubMed

25.

Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentral

26.

Lezak MD, Howison DB, Loring DW (2004) Neuropsychological assessment, 4th edn. Oxford University Press, New York, pp 478–514

27.

Shin MS, Park SY, Park SR, Seol SH, Kwon JS (2006) Clinical and empirical applications of the Rey-Osterrieth Complex Figure Test. Nat Protoc 1:892–899CrossRefPubMed

28.

Trenerry MR (1989) Stroop neuropsychological assessment manual. Psychological Assessment Resources, Odessa

29.

Rothman DL, Behar KL, Prichard JW, Petroff OA (1997) Homocarnosine and the measurement of neuronal pH in patients with epilepsy. Magn Reson Med 38:924–929CrossRefPubMed

30.

Edden RA, Puts NA, Harris AD, Barker PB, Evans CJ (2014) Gannet: a batch-processing tool for the quantitative analysis of gamma-aminobutyric acid-edited MR spectroscopy spectra. J Magn Reson Imaging 40:1445–1452CrossRefPubMed

31.

Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20:45–57CrossRefPubMed

32.

Montelius ML, Carlsson A, Stark G (2008) Matlab tool for segmentation and recreation of H-MRS volumes of interest in MRI image stacks. ESMRMB October 1–3, Antalya/TR

33.

Rae CD (2014) A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res 39:1–36CrossRefPubMed

34.

Rossi S, Muzio L, De Chiara V et al (2011) Impaired striatal GABA transmission in experimental autoimmune encephalomyelitis. Brain Behav Immun 25:947–956CrossRefPubMed

35.

Falco A, Pennucci R, Brambilla E, de Curtis I (2014) Reduction in parvalbumin-positive interneurons and inhibitory input in the cortex of mice with experimental autoimmune encephalomyelitis. Exp Brain Res 232:2439–2449CrossRefPubMedPubMedCentral

36.

Dutta R, McDonough J, Yin X et al (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 59:478–489CrossRefPubMed

37.

Clements RJ, McDonough J, Freeman EJ (2008) Distribution of parvalbumin and calretinin immunoreactive interneurons in motor cortex from multiple sclerosis post-mortem tissue. Exp Brain Res 187:459–465CrossRefPubMed

38.

Nicholas R, Magliozzi R, Campbell G, Mahad D, Reynolds R (2016) Temporal lobe cortical pathology and inhibitory GABA interneuron cell loss are associated with seizures in multiple sclerosis. Mult Scler 22:25–35CrossRefPubMedPubMedCentral

39.

Marenco S, Savostyanova AA, van der Veen JW et al (2010) Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT. Neuropsychopharmacology 35:1708–1717CrossRefPubMedPubMedCentral

40.

Massella A, D'Intino G, Fernandez M et al (2012) Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis. BMC Neurosci 13:12CrossRefPubMedPubMedCentral

41.

Nistico R, Mango D, Mandolesi G et al (2013) Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis. PLoS ONE 8:e54666CrossRefPubMedPubMedCentral

42.

Bibolini MJ, Chanaday NL, Baez NS, Degano AL, Monferran CG, Roth GA (2011) Inhibitory role of diazepam on autoimmune inflammation in rats with experimental autoimmune encephalomyelitis. Neuroscience 199:421–428CrossRefPubMed

43.

Carmans S, Hendriks JJ, Slaets H et al (2013) Systemic treatment with the inhibitory neurotransmitter gamma-aminobutyric acid aggravates experimental autoimmune encephalomyelitis by affecting proinflammatory immune responses. J Neuroimmunol 255:45–53CrossRefPubMed

44.

Gilani AA, Dash RP, Jivrajani MN, Thakur SK, Nivsarkar M (2014) Evaluation of GABAergic transmission modulation as a novel functional target for management of multiple sclerosis: exploring inhibitory effect of GABA on glutamate-mediated excitotoxicity. Adv Pharmacol Sci 2014:632376PubMedPubMedCentral

45.

Nantes JC, Proulx S, Zhong J et al (2017) GABA and glutamate levels correlate with MTR and clinical disability: insights from multiple sclerosis. NeuroImage. https://doi.org/10.1016/j.neuroimage.2017.01.033

46.

Gonzalez-Burgos G, Fish KN, Lewis DA (2011) GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia. Neural Plast 2011:723184CrossRefPubMedPubMedCentral

47.

Boy F, Evans CJ, Edden RA, Singh KD, Husain M, Sumner P (2010) Individual differences in subconscious motor control predicted by GABA concentration in SMA. Curr Biol 20:1779–1785CrossRefPubMedPubMedCentral

48.

Mullins PG, McGonigle DJ, O'Gorman RL et al (2014) Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. NeuroImage 86:43–52CrossRefPubMed

Titel: Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis
verfasst von: Guanmei Cao
Richard A. E. Edden
Fei Gao
Hao Li
Tao Gong
Weibo Chen
Xiaohui Liu
Guangbin Wang
Bin Zhao
Publikationsdatum: 06.10.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: European Radiology / Ausgabe 3/2018
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-017-5064-9

Neu im Fachgebiet Radiologie

18.04.2024 | Pädiatrische Notfallmedizin | Nachrichten

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

Abstract

Objectives

Methods

Results

Conclusions

Key points

Neu im Fachgebiet Radiologie

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

„Nur wer sich gut aufgehoben fühlt, kann auch für Patientensicherheit sorgen“

Wie toxische Männlichkeit der Gesundheit von Männern schadet

Studie bestätigt Potenzial von KI in der Radiologie

Update Radiologie

Springer Medizin

Abstract

Objectives

Methods

Results

Conclusions

Key points

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2018

Lateral epicondylitis: Associations of MR imaging and clinical assessments with treatment options in patients receiving conservative and arthroscopic managements

The effects of mild germinal matrix-intraventricular haemorrhage on the developmental white matter microstructure of preterm neonates: a DTI study

Differentiation of benign and malignant solid pancreatic masses using magnetic resonance elastography with spin-echo echo planar imaging and three-dimensional inversion reconstruction: a prospective study

Serial automated quantitative CT analysis in idiopathic pulmonary fibrosis: functional correlations and comparison with changes in visual CT scores

Baseline and annual repeat rounds of screening: implications for optimal regimens of screening

Self-controlled super-selective arterial spin labelling

Neu im Fachgebiet Radiologie

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

„Nur wer sich gut aufgehoben fühlt, kann auch für Patientensicherheit sorgen“

Wie toxische Männlichkeit der Gesundheit von Männern schadet

Studie bestätigt Potenzial von KI in der Radiologie

Update Radiologie