title: pH as a biomarker of neurodegeneration in Huntington's disease: a translational rodent-human MRS study.
abstract: Early diagnosis and follow-up of neurodegenerative diseases are often hampered by the lack of reliable biomarkers. Neuroimaging techniques like magnetic resonance spectroscopy (MRS) offer promising tools to detect biochemical alterations at early stages of degeneration. Intracellular pH, which can be measured noninvasively by (31)P-MRS, has shown variations in several brain diseases. Our purpose has been to evaluate the potential of MRS-measured pH as a relevant biomarker of early degeneration in Huntington's disease (HD). We used a translational approach starting with a preclinical validation of our hypothesis before adapting the method to HD patients. (31)P-MRS-derived cerebral pH was first measured in rodents during chronic intoxication with 3-nitropropionic acid (3NP). A significant pH increase was observed early into the intoxication protocol (pH=7.17±0.02 after 3 days) as compared with preintoxication (pH=7.08±0.03). Furthermore, pH changes correlated with the 3NP-induced inhibition of succinate dehydrogenase and preceded striatum lesions. Using a similar MRS approach implemented on a clinical MRI, we then showed that cerebral pH was significantly higher in HD patients (n=7) than in healthy controls (n=6) (7.05±0.03 versus 7.02±0.01, respectively, P=0.026). Altogether, both preclinical and human data strongly argue in favor of MRS-measured pH being a promising biomarker for diagnosis and follow-up of HD.
authors.affiliation: 1] Commissariat à l'Energie Atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center, Centre National de la Recherche Scientifique, Unité de Recherche Associée, Fontenay-aux-Roses Cedex, France [2] Institut de Myologie, Laboratoire de RMN, Paris, France.
authors.forename: Myriam M
authors.initials: MM
authors.lastname: Chaumeil
authors.forename: Julien
authors.initials: J
authors.lastname: Valette
authors.forename: Céline
authors.initials: C
authors.lastname: Baligand
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Brouillet
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.forename: Gilles
authors.initials: G
authors.lastname: Bloch
authors.forename: Véronique
authors.initials: V
authors.lastname: Gaura
authors.forename: Amandine
authors.initials: A
authors.lastname: Rialland
authors.forename: Pierre
authors.initials: P
authors.lastname: Krystkowiak
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.forename: Philippe
authors.initials: P
authors.lastname: Damier
authors.forename: Philippe
authors.initials: P
authors.lastname: Remy
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Bachoud-Levi
authors.forename: Pierre
authors.initials: P
authors.lastname: Carlier
authors.forename: Vincent
authors.initials: V
authors.lastname: Lebon
mesh_terms: D000328:Adult; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009574:Nitro Compounds / Q000009:adverse effects / Q000494:pharmacology; D011422:Propionates / Q000009:adverse effects / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid