Altered Sphingolipid Hydrolase Activities and Alpha-Synuclein Level in Late-Onset Schizophrenia
Tatiana Usenko,
Anastasia Bezrukova,
Katerina Basharova,
Galina Baydakova,
Elena Shagimardanova,
Nataliya Blatt,
Albert Rizvanov,
Oleg Limankin,
Maxim Novitskiy,
Natalia Shnayder,
Artem Izyumchenko,
Mikhail Nikolaev,
Anna Zabotina,
Anna Lavrinova,
Darya Kulabukhova,
Regina Nasyrova,
Ekaterina Palchikova,
Natalia Zalutskaya,
Irina Miliukhina,
Yury Barbitoff,
Oleg Glotov,
Andrey Glotov,
Anastasia Taraskina,
Nikolai Neznanov,
Ekaterina Zakharova,
Sofya Pchelina
Affiliations
Tatiana Usenko
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Anastasia Bezrukova
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Katerina Basharova
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre Kurchatov Institute, 188300 Gatchina, Russia
Galina Baydakova
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre Kurchatov Institute, 188300 Gatchina, Russia
Elena Shagimardanova
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
Nataliya Blatt
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
Albert Rizvanov
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
Oleg Limankin
Psychiatric Hospital No. 1 Named after P. P. Kashchenko, 195009 Saint Petersburg, Russia
Maxim Novitskiy
Center for Personalized Psychiatry and Neurology of the N.N. V.M. Bekhtereva, 192019 Saint Petersburg, Russia
Natalia Shnayder
Center for Personalized Psychiatry and Neurology of the N.N. V.M. Bekhtereva, 192019 Saint Petersburg, Russia
Artem Izyumchenko
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Mikhail Nikolaev
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Anna Zabotina
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Anna Lavrinova
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre Kurchatov Institute, 188300 Gatchina, Russia
Darya Kulabukhova
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Regina Nasyrova
Center for Personalized Psychiatry and Neurology of the N.N. V.M. Bekhtereva, 192019 Saint Petersburg, Russia
Ekaterina Palchikova
V.M. Bekhterev National Medical Research Center Psychiatry and Neurology, 192019 Saint Petersburg, Russia
Natalia Zalutskaya
V.M. Bekhterev National Medical Research Center Psychiatry and Neurology, 192019 Saint Petersburg, Russia
Irina Miliukhina
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Yury Barbitoff
D.O. Ott Research Institute for Obstetrics, Gynecology, and Reproductology, 199034 Saint Petersburg, Russia
Oleg Glotov
D.O. Ott Research Institute for Obstetrics, Gynecology, and Reproductology, 199034 Saint Petersburg, Russia
Andrey Glotov
D.O. Ott Research Institute for Obstetrics, Gynecology, and Reproductology, 199034 Saint Petersburg, Russia
Anastasia Taraskina
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Nikolai Neznanov
Center for Personalized Psychiatry and Neurology of the N.N. V.M. Bekhtereva, 192019 Saint Petersburg, Russia
Ekaterina Zakharova
Research Center for Medical Genetics, 115478 Moscow, Russia
Sofya Pchelina
Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia
Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features of schizophrenia (SCZ) have been demonstrated in patients with several lysosomal storage disorders (LSDs). Taking into account the critical role of lysosomal function for neuronal cells’ lysosomal dysfunction could be proposed in SCZ pathogenesis. The current study analyzed lysosomal enzyme activities and the alpha-synuclein level in the blood of patients with late-onset SCZ. In total, 52 SCZ patients with late-onset SCZ, 180 sporadic Parkinson’s disease (sPD) patients, and 176 controls were recruited. The enzymatic activity of enzymes associated with mucopolysaccharidosis (alpha-L-Iduronidase (IDUA)), glycogenosis (acid alpha-glucosidase (GAA)) and sphingolipidosis (galactosylceramidase (GALC), glucocerebrosidase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase)) and concentration of lysosphingolipids (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), and lysosphingomyelin (LysoSM)) were measured using LC-MS/MS. The alpha-synuclein level was estimated in magnetically separated CD45+ blood cells using the enzyme-linked immunosorbent assay (ELISA). Additionally, NGS analysis of 11 LSDs genes was conducted in 21 early-onset SCZ patients and 23 controls using the gene panel PGRNseq-NDD. Decreased ASMase, increased GLA activities, and increased HexSpn, LysoGb3, and LysoSM concentrations along with an accumulation of the alpha-synuclein level were observed in late-onset SCZ patients in comparison to the controls (p IDUA (rs532731688, rs74385837) and type III (HGSNAT (rs766835582)) and sphingolipidosis (metachromatic leukodystrophy (ARSA (rs201251634)) were identified in five patients from the group of early-onset SCZ patients but not in the controls. Our findings supported the role of sphingolipid metabolism in SCZ pathogenesis. Aberrant enzyme activities and compounds of sphingolipids associated with ceramide metabolism may lead to accumulation of alpha-synuclein and may be critical in SCZ pathogenesis.
