alpha-synuclein and Anxiety-Disorders

Parkinson's disease (PD) is a prevalent motor disease caused by the accumulation of mutated α-synuclein (α-Syn); however, its early stages are also characterized by non-motor symptoms, such as olfactory loss, cognitive decline, depression, and anxiety. The therapeutic effects of environmental enrichment (EE) on motor recovery have been reported, but its effects on non-motor symptoms remain unclear. Herein, we reveal the beneficial effects of EE on PD-related non-motor symptoms and changes in synaptic plasticity in the nucleus accumbens. To investigate its therapeutic effects in the early phase of PD, we randomly assigned eight-month-old mice overexpressing human A53T (hA53T) α-Syn to either the EE or standard condition groups for two months. Next, we performed behavioral tests and biochemical and histological analyses at 10 months of age. EE significantly alleviated locomotor hyperactivity and anxiety during the early stages of PD. It normalized the levels of tyrosine hydroxylase, phosphorylated and oligomeric α-Syn, and soluble

Topics: alpha-Synuclein; Animals; Anxiety; Anxiety Disorders; Disease Models, Animal; Humans; Locomotion; Mice; Mice, Transgenic; Parkinson Disease; Tyrosine 3-Monooxygenase; Vesicle-Associated Membrane Protein 2

Vitamin A has been characterized as a potential neurotoxin, because ingestion of such vitamin - or its derivatives, the retinoids - at moderate to high doses elicits a myriad of deleterious effects, from acute intoxication involving head-ache, confusion, and 'pseudo tumor cerebri' to chronic, and perhaps irreversible, abnormalities, including irritability, anxiety, depression, and suicide ideation. Nevertheless, it still remains to be found the mechanism by which vitamin A induces cognitive decline. Based on the fact that vitamin A at clinical doses is a potent pro-oxidant agent to the central nervous system, we performed the present work to analyze whether a cotreatment with L-NAME at 30 mg/kg (four times a week) was able to prevent (or minimize) the biochemical and/or behavioral disturbances resulting from a 28-day daily supplementation with retinol palmitate at doses from 1000 to 9000 IU/kg/day. Then, we investigated mitochondrial function, redox parameters, and the levels of proteins potentially involved in neurodegenerative events, as for instance α-synuclein and receptor for advanced glycation endproducts. Besides, monoamine oxidase enzyme activity was quantified in this work. We observed that L-NAME cotreatment was not completely effective in preventing the redox disturbances induced by vitamin A supplementation. Moreover, L-NAME cotreatment did not affect the behavioral deficits elicited by vitamin A supplementation. We conclude that other parameters rather than NO levels or its derivatives, as for example ONOO(-), take a more important role in mediating the negative effects triggered by vitamin A supplementation.

Topics: alpha-Synuclein; Animals; Anxiety Disorders; Behavior, Animal; Central Nervous System; Dietary Supplements; Diterpenes; Electron Transport; Glutathione Transferase; Heat-Shock Proteins; Illness Behavior; Locomotion; Male; Manganese; Mitochondria; Monoamine Oxidase; Neurodegenerative Diseases; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidation-Reduction; Rats; Rats, Wistar; Receptor for Advanced Glycation End Products; Receptors, Dopamine; Receptors, Immunologic; Retinyl Esters; Superoxide Dismutase; Superoxides; Tyrosine; Vitamin A