Abstract
The cerebellum harbors a circadian clock that can be shifted by scheduled mealtime and participates in behavioral anticipation of food access. Large-scale two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry was used to identify day–night variations in the cerebellar proteome of mice fed either during daytime or nighttime. Experimental conditions led to modified expression of 89 cerebellar proteins contained in 63 protein spots. Five and 33 spots were changed respectively by time-of-day or feeding conditions. Strikingly, several proteins of the heat-shock protein family (i.e., Hsp90aa1, 90ab1, 90b1, and Hspa2, 4, 5, 8, 9) were down-regulated in the cerebellum of daytime food-restricted mice. This was also the case for brain fatty acid protein (Fabp7) and enzymes involved in oxidative phosphorylation (Ndufs1) or folate metabolism (Aldh1l1). In contrast, aldolase C (Aldoc or zebrin II) and pyruvate carboxylase (Pc), two enzymes involved in carbohydrate metabolism, and vesicle-fusing ATPase (Nsf) were up-regulated during daytime restricted feeding, possibly reflecting increased neuronal activity. Significant feeding × time-of-day interactions were found for changes in the intensity of 20 spots. Guanine nucleotide-binding protein G(o) subunit alpha (Gnao1) was more expressed in the cerebellum before food access. Neuronal calcium-sensor proteins [i.e., parvalbumin (Pvalb) and visinin-like protein 1 (Vsnl1)] were inversely regulated in daytime food-restricted mice, compared to control mice fed at night. Furthermore, expression of three enzymes modulating the circadian clockwork, namely heterogeneous nuclear ribonucleoprotein K (Hnrnpk), serine/threonine-protein phosphatases 1 (Ppp1cc and Ppp1cb subunits) and 5 (Ppp5), was differentially altered by daytime restricted feeding. Besides cerebellar proteins affected only by feeding conditions or daily cues, specific changes in in protein abundance before food access may be related to behavioral anticipation of food access and/or feeding-induced shift of the cerebellar clockwork.
Highlights
The main functions and behaviors, such as food intake and sleep, display circadian rhythms
Scheduled meal times at odd times can shift the cerebellar clockwork (Mendoza et al, 2010; Delezie et al, 2016), indicating that circadian oscillations in the cerebellum are sensitive to the synchronizing effects of meal time
Functional annotation analysis revealed that these differences between mice groups involve mostly proteins that are known to play a role in the following broad functions: synapse and trafficking, the metabolisms for nucleotides, carbohydrates, proteins and amino acids, and energy metabolism and the mitochondrial function (Figure 2)
Summary
The main functions and behaviors, such as food intake and sleep, display circadian rhythms (i.e., endogenous rhythms close to 24 h) These rhythms are generated by internal clocks that allow cells, organs and the whole organism to anticipate and adapt to predictable changes in the environment. Contrary to what happens in suprachiasmatic cells of the master clock (Brown and Piggins, 2007), the cerebellar clock does not appear to regulate rhythmic properties of neuronal membranes (Mordel et al, 2013). The role of this hindbrain clock for cerebellar function is not fully elucidated yet, it may modulate efficiency of motor coordination on a daily basis. Scheduled meal times at odd times (i.e., food access limited to daytime, corresponding to the resting period in nocturnal mice and rats) can shift the cerebellar clockwork (Mendoza et al, 2010; Delezie et al, 2016), indicating that circadian oscillations in the cerebellum are sensitive to the synchronizing effects of meal time
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
