title: Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.
abstract: The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Beitnere
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia.
authors.forename: Zane
authors.initials: Z
authors.lastname: Dzirkale
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga, LV-1586, Latvia; Riga East University Hospital, Center of Pathology, 2 Hipokrata str., LV-1038 Riga, Latvia.
authors.forename: Sergejs
authors.initials: S
authors.lastname: Isajevs
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia.
authors.forename: Juris
authors.initials: J
authors.lastname: Rumaks
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia.
authors.forename: Simons
authors.initials: S
authors.lastname: Svirskis
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia. Electronic address: vijaklus@latnet.lv.
authors.forename: Vija
authors.initials: V
authors.lastname: Klusa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology; D058851:GPI-Linked Proteins / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008763:Methylhydrazines / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; D008763:Methylhydrazines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C050147:3-(2,2,2-trimethylhydrazine)propionate; D000110:Acetylcholinesterase; C548246:Ache protein, rat; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D006220:Haloperidol; D002331:Carnitine
keywords: Haloperidol; Haloperidol (PubChem CID: 3559); Memory; Mildronate; Mildronate (PubChem CID: 123868); Protein expression; Stress