Behavioral and Biochemical Effects of an Arylhydrazone Derivative of 5-Methoxyindole-2-Carboxylic Acid in a Scopolamine-Induced Model of Alzheimer’s Type Dementia in Rats
Polina Petkova-Kirova,
Neda Anastassova,
Borislav Minchev,
Diamara Uzunova,
Valya Grigorova,
Elina Tsvetanova,
Almira Georgieva,
Albena Alexandrova,
Miroslava Stefanova,
Denitsa Yancheva,
Reni Kalfin,
Lyubka Tancheva
Affiliations
Polina Petkova-Kirova
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Neda Anastassova
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Building 9, 1113 Sofia, Bulgaria
Borislav Minchev
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Diamara Uzunova
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Valya Grigorova
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Elina Tsvetanova
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Almira Georgieva
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Albena Alexandrova
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Miroslava Stefanova
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Denitsa Yancheva
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Building 9, 1113 Sofia, Bulgaria
Reni Kalfin
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Lyubka Tancheva
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113 Sofia, Bulgaria
Alzheimer’s disease (AD) has long proven to be a complex neurodegenerative disorder, with cholinergic dysfunction, oxidative stress, and neuroinflammation being just a few of its pathological features. The complexity of the disease requires a multitargeted treatment covering its many aspects. In the present investigation, an arylhydrazone derivative of 5-methoxyindole-2-carboxylic acid (5MeO), with in vitro strong antioxidant, neuroprotective and monoamine oxidase B-inhibiting effects, was studied in a scopolamine-induced Alzheimer-type dementia in rats. Using behavioral and biochemical methods, we evaluated the effects of 5MeO on learning and memory, and elucidated the mechanisms of these effects. Our experiments demonstrated that 5MeO had a beneficial effect on different types of memory as assessed by the step-through and the Barnes maze tasks. It efficiently restored the decreased by scopolamine brain-derived neurotrophic factor and acetylcholine levels and normalized the increased by scopolamine acetylcholine esterase activity in hippocampus. Most effective 5MeO was in counteracting the induced by scopolamine oxidative stress by decreasing the increased by scopolamine levels of lipid peroxidation and by increasing the reduced by scopolamine catalase activity. Blood biochemical analyses demonstrated a favorable safety profile of 5MeO, prompting further pharmacological studies suggesting 5MeO as a safe and efficient candidate in a multitargeted treatment of AD.
