ABSTRACT
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Among its non-motor symptoms, sleep disorders are extremely common, being linked to cognitive and memory disruption. The microenvironment, particularly the extracellular matrix (ECM), is deeply involved in memory consolidation as well as in neuropathological processes, such as inflammation, damage to the blood-brain barrier and neuronal death. To better understand ECM dynamics in PD memory disturbances, we investigated the orchestrated expression of Mmps (Mmp-3, Mmp-7, and Mmp-9) and their modulators (Reck and Timp-3) in a rotenone-induced PD model. Also, we introduced an additional intervention in the memory process through rapid eye movement sleep deprivation (REMSD). We observed a REMSD-induced trend in reversing the memory impairment caused by rotenone administration. Associated to this phenotype, we observed a significant increase in Mmp-7/Reck and Mmp-9/Reck mRNA expression ratio in the substantia nigra and Mmp-9/Reck ratio in the hypothalamus. Moreover, the positive correlation of Mmp/Reck expression ratios between the substantia nigra and the striatum, observed upon rotenone infusion, was reversed by REMSD. Taken together, our results suggest a potential orchestrated association between an increase in Mmp-7 and Mmp-9/Reck expression ratios in the substantia nigra and a possible positive effect on cognitive performance in subjects affected by PD.
Subject(s)
Gene Expression Regulation , Matrix Metalloproteinases/genetics , Memory , Parkinson Disease/genetics , Parkinson Disease/physiopathology , Recognition, Psychology , Tumor Suppressor Proteins/genetics , Animals , Brain/metabolism , Disease Models, Animal , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Male , Matrix Metalloproteinases/metabolism , Rats, Wistar , Tumor Suppressor Proteins/metabolismABSTRACT
Epidemiological and dietary studies show that nutritional deficit of omega-3 polyunsaturated fatty acids (ω-3 PUFA) is directly related to the prevalence and severity of depression. Supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) during critical periods of development (pregnancy and lactation) is essential for cortical maturation, synaptogenesis and myelination, and may also mitigate the risk for cognitive deficits and psychopathologies in young adults. The present study was performed to evaluate the involvement of serotonin (5-HT) receptors, particularly of 5-HT(1A), and hippocampal brain-derived neurotrophic factor (BDNF) expression in the antidepressant effect of ω-3 PUFA supplementation. In Experiment 1, the antidepressant effects of fish oil were assessed by the modified forced swim test in adult rats. The data indicated a robust antidepressant effect produced by this supplementation and that treatment of the rats with WAY 100135 reversed this effect. In Experiment 2, cortical and hippocampal contents of BDNF, 5-HT, dopamine (DA) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), and 3,4-dihydroxyphenylacetic acid (DOPAC), were determined in animals subjected to the same protocol. Increased BDNF expression in the cortex and hippocampus of both age groups was detected. In 90 day-old rats, 5-HT content in the hippocampus was increased, whereas 5-HIAA formation was diminished in the fish oil group. We suggest the occurrence of a reciprocal involvement of 5-HT(1A) receptors activation and the hippocampal BDNF-increased expression mediated by fish oil supplementation. These data corroborate and expand the notion that supplementation with ω-3 PUFA produces antidepressant effects mediated by an increase in serotonergic neurotransmission, particularly in the hippocampus. This article is part of a Special Issue entitled 'Anxiety and Depression'.