Rani elektrofiziološki znaci poremećaja spavanja i motorne kontrole u starenju pacova sa neurodegeneracijom holinergičkih neurona

Abstract

Cilj ove doktorske disertacije bio je da ispita uticaj starenja na spavanje u eksperimentalnim modelima holinergičke neuropatologije Alchajmerove i Parkinsonove bolesti, i da pronađe najranije znake poremećaja spavanja u fiziološkom starenju i u starenju sa neurodegenerativnim bolestima. Uticaj starenja na arhitekturu spavanja, elektroencefalografsku (EEG) mikrostrukturu i motornu kontrolu, u toku svake faze spavanja, je praćen u eksperimentalnim modelima bilateralnih oštećenja jedara nucleus basalis (NB) i nucleus pedunculopontinus tegmentalis (PPT) u pacova, kao eksperimentalnim in vivo modelima funkcionalno različitih holinergičkih neuropatologija. Fiziološko starenje dovodi do topografski različitih promena arhitekture spavanja i motorne kontrole iz senzomotorne kore (SMCx) u odnosu na motornu koru (MCx). Pored promena arhitekture spavanja koje su se javile samo u SMCx, fiziološko starenje dovodi i do povećanja propagacije delta i beta oscilacija iz obe kore za vreme budnosti, ali samo iz MCx za vreme REM faze spavanja. Najraniji znaci starenja u eksperimentalnim modelima funkcionalno različitih holinergičkih neuropatologija, dokazani po prvi put, predstavljaju topografski specifične razlike u EEG mikrostrukturi za vreme REM faze spavanja. Smanjenje delta EEG relativne amplitude u SMCx predstavlja najraniji znak starenja kod NB lediranih pacova, dok povećanje sigma EEG relativne amplitude u MCx predstavlja najraniji znak starenja kod PPT lediranih pacova, za vreme REM faze spavanja. Pored toga, starenjem izazvane promene su različito izražene kroz mišićnu kontrolu iz SMCx, a istovremeno i istovetno izražene iz MCx u toku svih faza spavanja...

The aim of the present doctoral dissertation was to evaluate the impact of aging during sleep in the rat models of Alzheimer’s and Parkinson’s disease cholinergic neuropathology, and to determine the possible different and earlier onset of age-related sleep disorder during healthy aging and aging with the neurodegenerative diseases. We used the bilateral nucleus basalis (NB) and nucleus pedunculopontinus tegmentalis (PPT) lesioned rats as the in vivo models of functionally distinct cholinergic neuropathology, and we followed the impact of aging on sleep architecture, the electroencephalographic (EEG) microstructure and motor control across sleep/wake states. We evidenced the topographically distinct impact of healthy aging on sleep architecture and motor control within the sensorimotor (SMCx) vs. motor cortex (MCx). Whereas healthy aging consistently altered only the SMCx sleep architecture, it increased the delta and beta cortical drives from both cortices during Wake, but only through the MCx drive during rapid eye movement sleep (REM). Our results have shown for the first time that the earliest signs of aging during distinct cholinergic neuropathology were expressed through a different and topographically specific EEG microstructure during REM. EEG delta amplitude attenuation within the SMCx was the earliest sign of aging in the NB lesion, whereas EEG sigma amplitude augmentation within the MCx was the earliest sign of aging in the PPT lesion during REM. In addition, aging was differently expressed through the SMCx drive alterations, but it was commonly expressed through the MCx drive alterations during all sleep/wake states...