Behavioral changes of transgenic mice carrying Adrb1-A187V mutation with short sleep duration under different dietary conditions

doi:10.12122/j.issn.1673-4254.2024.10.07

Abstract

Abstract:

Objective To observe the effects of restricted and high-fat diets on behavioral changes of wild-type (Adrb1^+/+) and transgenic mice carrying Adrb1-A187V mutation (Adrb1^+/m) with short sleep durations. Methods Adrb1^+/+ and Adrb1^+/m C57BL/6 mice were randomized into normal chow group (25 Adrb1^+/+ and 26 Adrb1^+/m mice for behavioral monitoring), odor retention fasting group (17 Adrb1^+/+ and 19 Adrb1^+/m mice for behavioral monitoring; 6 Adrb1^+/+ mice and 6 Adrb1^+/m mice for EEG/EMG monitoring), absolute fasting group (6 Adrb1^+/+ and 4-5 Adrb1^+/m mice for behavioral monitoring; 6 Adrb1^+/+ and 6 Adrb1^+/m mice for EEG/EMG monitoring), and high-fat diet group (6 Adrb1^+/+ and 7 Adrb1^+/m mice for behavioral monitoring; 6 Adrb1^+/+ and 6 Adrb1^+/m mice for EEG/EMG monitoring). Electrodes for EEG and muscle activity monitoring were implanted on the skulls of the mice. After 24 h of odor retention fasting, absolute fasting, or high-fat feeding, the mice were observed for behavioral changes adapted to diet changes. Results In odor retention fasting experiment, Adrb1^+/m mice exhibited more stable fluctuations of activities with mildly reduced movement and prolonged sleep duration, indicating enhanced starvation resistance. In absolute fasting experiment, Adrb1^+/m mice showed significantly increased nighttime water intake, improved rhythmicity in water intake (frequent intakes in small amounts), and increased duration of non-rapid eye movement sleep (NREM). In the high-fat diet experiment, Adrb1^+/m mice showed higher levels of activity with increased instances of nighttime rearing, longer movement distances, and increased rapid eye movement sleep during daytime. Conclusion Adrb1^+/m mice can quickly respond to environmental changes and under restricted dietary conditions, they can conserve energy by increasing sleep to maintain energy homeostasis but show higher levels of activity under high-fat dietary conditions.

Key words: short sleep gene, sleep, feeding, energy homeostasis, Adrb1-A187V mutation

Ziping SONG, Lei HAN, Zhuochao LIN, Guangsen SHI. Behavioral changes of transgenic mice carrying Adrb1-A187V mutation with short sleep duration under different dietary conditions[J]. Journal of Southern Medical University, 2024, 44(10): 1887-1897.

Figures/Tables 9

Tab.1 PCR program setting

Stage	Temperature (℃)	Time	Cycle
1	95	3 min	1×
	95	30 s
2	60	30 s	35×
	72	30 s
3	72	5 min	1×
4	16	∞	1×

Fig.1 Activity and food/water intake of Adrb1+/+ and Adrb1+/m mice with free access to normal chow. A: Schematic of the mouse behavioral and feeding/drinking recording system. B: Total daily amount of food intake of Adrb1+/+ and Adrb1+/m mice. C: Total amount of food intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phases. D: Daily number of "big meal", " medium meal" and "small meal" in Adrb1+/+ and Adrb1+/m mice. E: Total daily amount of water intake of Adrb1+/+ and Adrb1+/m mice. F: Total amount of wake intake of Adrb1+/+ and Adrb1+/m mice in dark and light phases. G: Daily numbers of "big water", " medium water " and "small water " in Adrb1+/+ and Adrb1+/m mice. H: Total daily numbers of rearing of Adrb1+/+ and Adrb1+/m mice. I: Total daily distance traveled by Adrb1+/+ and Adrb1+/m mice. Adrb1+/+ mice (n=25), Adrb1+/m mice (n=26), **P<0.01.

Fig.2 Changes in food intake and activity of Adrb1+/+ and Adrb1+/m mice during and after odor-retention fasting regime. A: Total daily food intake of Adrb1+/+ and Adrb1+/m mice during NC and Refeed. B: Total daily water intake of Adrb1+/+ and Adrb1+/m mice during NC, RF, and Refeed. C: Water intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under RF conditions. D: Total daily number of "big water", "medium water " and "small water" of Adrb1+/+ and Adrb1+/m mice under RF conditions. E: Total daily number of rears of Adrb1+/+ and Adrb1+/m mice during NC, RF and Refeed. F: Total daily distance traveled by Adrb1+/+ and Adrb1+/m mice under NC, RF, and Refeed. G: Time course recording of food intake after odor retention fasting (RF) plotted every 5 min for 90 minu in Adrb1+/+ and Adrb1+/m mice. Adrb1+/+ mice (n=17), Adrb1+/m mice (n=19). NC: Normal condition; RF: Odor retetion fasting. *P<0.05, **P<0.01, ****P<0.0001.

Fig.3 Sleep changes in Adrb1+/+ and Adrb1+/m mice under odor retention fasting condition. A: The multichannel EEG recording system. B-D: Total Wake (B), NREM (C), and REM (D) sleep time of Adrb1+/+ mice in the dark and light phase under NC and RF conditions. E-G: Total Wake (E), NREM (F), and REM (G) sleep time of Adrb1+/m mice in the dark and light phase under NC and RF conditions. Adrb1+/+ mice (n=6), Adrb1+/m mice (n=6), *P<0.05, **P<0.01.

Fig.4 Changes in food intake and activity of Adrb1+/+ and Adrb1+/m mice during and after absolute fasting condition (AF). A: Total daily food intake of Adrb1+/+ and Adrb1+/m mice during NC and Refeed. B: Total daily water intake of Adrb1+/+ and Adrb1+/m mice during NC, AF, and Refeed. C: Water intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under AF conditions. D: Total daily number of "big water", " medium water " and "small water " of Adrb1+/+ and Adrb1+/m mice under AF conditions. E: Total daily number of rears of Adrb1+/+ and Adrb1+/m mice during NC, AF and Refeed. F: Total daily distance traveled by Adrb1+/+ and Adrb1+/m mice under NC, AF, and Refeed. G: Time course recording of food intake after absolute fasting (AF) plotted every 5 min for 90 min in Adrb1+/+ and Adrb1+/m mice. Adrb1+/+ mice (n=6), Adrb1+/m mice (n=4-5), *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig.5 Sleep changes in Adrb1+/+ and Adrb1+/m mice under absolute fasting (AF) condition. A-C: Total Wake (A), NREM (B), and REM (C) sleep time of Adrb1+/+ mice in the dark and light phase under NC and AF conditions. D-F: Total Wake (D), NREM (E), and REM (F) sleep time of Adrb1+/m mice in the dark and light phase under NC and AF conditions. Adrb1+/+ mice (n=6), Adrb1+/m mice n=6), *P<0.05, **P<0.01, ***P<0.001.

Fig.6 Effects of high-fat diet (HF) on feeding and drinking behaviors in Adrb1+/+ and Adrb1+/m mice. A: Total daily food intake of Adrb1+/+ and Adrb1+/m mice during NC, HF d1 and HF d14. B: Food intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d1. C: Total daily water intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d14. D: Total daily water intake of Adrb1+/+ and Adrb1+/m mice during NC、HF d1 and HF d14. E: Water intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d1. F: Water intake of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d14. G: Total daily number of "big water", "medium water " and "small water " of Adrb1+/+ and Adrb1+/m mice under HF d1 conditions. H: Total daily number of "big water", " medium water " and "small water " in Adrb1+/+ and Adrb1+/m mice under HF d14 conditions. Adrb1+/+ mice (n=6), Adrb1+/m mice (n=7, except n=4 for drinking at HF d14, E G I), *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig.7 Effects of high-fat diet (HF) on locomotor activity of Adrb1+/+ and Adrb1+/m mice. A: Total daily number of rears of Adrb1+/+ and Adrb1+/m mice during NC, HF d1 and HF d14. B: Rear bouts of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d1. C: Rear bouts of Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d14. D: Total daily distance traveled by Adrb1+/+ and Adrb1+/m mice under NC, HF D1 and HF d14. E: Distance traveled by Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d1. F: Distance traveled by Adrb1+/+ and Adrb1+/m mice in the dark and light phase under HF d14. Adrb1+/+ mice (n=6), Adrb1+/m mice (n=7), *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig.8 Sleep changes in Adrb1+/+ and Adrb1+/m mice under high-fat diet (HF) condition. A-C: Total Wake (A), NREM (B), and REM (C) sleep time in Adrb1+/+ mice in the dark and light phase under NC and HF conditions. D-F: Total Wake (D), NREM (E), and REM (F) sleep time in Adrb1+/m mice in the dark and light phase under NC and HF conditions. Data are presented as Mean±SE (n=6). **P<0.01.

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