Objective: 1. To test whether the alterations of REM sleep induced by lesions of the key areas involved in RBD pathogenesis are correlated to abnormalities of startle reflex and its modulatory processes in rat models. 2. To investigate whether startle abnormalities and RBD phenotypes concomitantly occur in the 6-OHDA rat model of PD.

Background: REM sleep behavior disorder (RBD) is a parasomnia results in loss of normal muscle atonia, vivid dreams and complex behaviors during REM sleep. Clinical investigations revealed that more than 90% of idiopathic RBD patients are prone to develop a synucleinopathy within 15 years. Accordingly, half of PD patients exhibit RBD with higher severity of PD symptoms, and increased risk for neuropsychiatric problems. Pathogenesis of RBD results from imbalances of excitatory and inhibitory inputs across several brainstem areas, such as the sublaterodorsal tegmental nucleus (SLD) and the pedunculopontine and laterodorsal tegmental complex. Interestingly, the same brain areas are involved in the modulation of startle reflex, an involuntary response consisting in muscular contraction in reaction to sudden sensory stimuli.

Method: Adult Sprague-Dawley rats were subjected to bilateral electrolytical lesions (kainic acid 0.5 mcg/side) of SLD and LTD/PPN, or infused unilaterally with 6-OHDA (16 mcg) in the Medial Forebrain Bundle (MFB) and implanted with electrodes for 24-hour polysomnography (PSG) testing. Rats were then tested for either PSG or acoustic startle reflex paradigms, including startle habituation and pre-pulse inhibition (PPI).

Results: The lesion of SLD and LTD-PPN significantly reduced startle amplitude (P < 0.01 and P < 0.001, respectively) and habituation (P < 0.001), but not PPI in comparison with sham-surgery group. Furthermore, animals subjected to LTD/PPN lesion exhibited more robust startle alterations than SLD and these alterations were accompanied by sleep behavioral abnormalities. The same startle modifications were found in hemiparkinsonian rats lesioned by unilateral infusion in the MFB of the neurotoxin 6-OHDA (P < 0.01 vs sham group).

Conclusion: Our preliminary data suggests that lesion of areas involved in RBD pathogenesis, LTD-PPN, SLD, and depletion of dopaminergic nigrostriatal pathway are associated with startle amplitude alterations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/startle-reflex-as-a-possible-biomarker-associated-with-rem-sleep-behavior-disorders-in-the-prodromal-stage-of-parkinsons-disease/