4 research outputs found
Perspectives for the association between olfactory disturbances and depression in Parkinson’s disease
Absence of a synergic nigral proapoptotic effect triggered by REM sleep deprivation in the rotenone model of Parkinson´s disease
Excitotoxicity has been related to play a crucial role in Parkinson’s disease (PD) pathogenesis.
Pedunculopontine tegmental nucleus (PPT) represents one of the major sources of glutamatergic
afferences to nigrostriatal pathway and putative reciprocal connectivity between these structures
may exert a potential influence on rapid eye movement (REM) sleep control. Also, PPT could
be overactive in PD, it seems that dopaminergic neurons are under abnormally high levels of
glutamate and consequently might be more vulnerable to neurodegeneration. We decided to
investigate the neuroprotective effect of riluzole administration, a N-methyl-D-aspartate (NMDA)
receptor antagonist, in rats submitted simultaneously to nigrostrial rotenone and 24h of REM
sleep deprivation (REMSD). Our findings showed that blocking NMDA glutamatergic receptors
in the SNpc, after REMSD challenge, protected the dopaminergic neurons from rotenone lesion.
Concerning rotenone-induced hypolocomotion, riluzole reversed this impairment in the control
groups. Also, REMSD prevented the occurrence of rotenone-induced motor impairment as a result
of dopaminergic supersensitivity. In addition, higher Fluoro Jade C (FJC) staining within the SNpc
was associated with decreased cognitive performance observed in rotenone groups. Such effect was
counteracted by riluzole suggesting the occurrence of an antiapoptotic effect. Moreover, riluzole did
not rescue cognitive impairment impinged by rotenone, REMSD or their combination. These data
indicated that reductions of excitotoxicity, by riluzole, partially protected dopamine neurons from
neuronal death and appeared to be effective in relieve specific rotenone-induce motor disabilities
Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.
Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies