Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice

Table 1

(a) The treadmill exercise exerted beneficial effects on the sensorimotor function which were more relevant in females

	M non-Tg	M TgSED	M TgEXE	F non-Tg	F TgSED	F TgEXE
	(𝑛=8)	(𝑛=10)	(𝑛=10)	(𝑛=8)	(𝑛=8)	(𝑛=8)
Body weight
Weight curve
Start of week 1 (g)	34.4±0.7	36.0±0.8	39.2±1.8	24.7±1.2	32.3±1.2	32.0±1.4
End of week 5 (g)	34.4±0.4	37.0±0.7	38.4±1.6^∗	23.8±0.3^∗	28.8±1.0^#	29.7±1.2^#
WAT (% versus body weight)	See Figure 1
Sensorimotor function
Reflex tests
Incidence of both reflexes	8/8	10/10	10/10	8/8	8/8	8/8
Wooden rod test
Equilibrium (mean latency to fall, s)	8.3±2.2	17.5±1.4	19.2±0.5	14.5±2.1	20.0±0.0	20.0±0.0
Coordination (mean distance, cm)	2.5+1.5	3.2±2.0	5.7±2.5	1.4±0.7^#	5.3±4.3^#	39.7±8.4^#
Wire rod test
Equilibrium (mean latency to fall, s)	3.0±0.5	9.4±1.9	9.8±1.7	3.5±0.8^#	15.4±1.6^#	16.7±1.6^#
Coordination (mean distance, cm)	0±0	0±0	5.3±4.0	0±0^#	0.9±0.9^#	19.7±6.6^#
Wire hang test (2 trials 5 s)
Strength (mean latency to fall, s)	0.9±0.1	4.1±0.4^∗	4.2±0.3^∗	0.9±0.3	4.5±0.2^∗	5.0±0.0^∗
Coordination (mean distance, cm)	0±0	0.5±0.3	0.6±0.4	0±0	0.3±0.3	1.1±0.3
Elements of support (𝑛)	1.1±0	1.5±0.4	1.2±0.3	0.8±0.1	1.25±0.4	2.3±0.4
Wire hang test (1 trial 60 s)
Strength (mean latency to fall, s)	4.0±2.6	34.1±7.6^∗	33.4±6.4^∗	1.0±0.1	55.7±4.2^#,∗	55.0±5.0^#,∗
Coordination (mean distance, cm)	0.3±0.3	2.4±0.6^∗	3.1±0.5^∗	0±0	5.0±1.7^∗	6.7±1.1^#,∗
Elements of support (𝑛)	1.7±0.3	2.4±0.3	2.4±0.3	1.1±0	2.8±0.2	3.0±0.0^#,∗

Note: non-Tg, nontransgenic mice; TgSED, 3xTgAD mice not exercised; TgEXE, 3xTg-AD mice submitted to a daily treadmill running for five weeks. The body weight, fat composition, and sensorimotor function of 3xTg-AD mice differed from that of non-Tg mice. The treadmill exercise exerted beneficial effects on the sensorimotor function which were more relevant in females. Results are the mean ± SEM, 𝑛=8-10 as indicated. Statistics: ^∗𝑃<.05 compared to non-Tg;^#𝑃<.01 compared to TgSED.

(b) BPSD-like behaviors are characteristic of 3xTg-AD mice at early stages of the disease and show an important gender component

	M non-Tg	M TgSED	M TgEXE	F non-Tg	F TgSED	F TgEXE
	(𝑛=8)	(𝑛=10)	(𝑛=10)	(𝑛=8)	(𝑛=8)	(𝑛=8)
Corner test
Vertical activity (latency, s)	5.0±1.5	16.3±7.4^∗	19.6±7.9^∗	8.9±4.7	5.3±1.7	10.5±4.1
Open-field test
Initial movement (latency, s)	7.2±1.3	3.3±1	1.9±0.6^∗	13.6±6.7	4.2±1.7	3.0±0.9
Exit of the center (latency, s)	14.2±2.3	10.7±2	5.2±1.1^∗	30.4±13.7	7.6±2.3	4.4±1.0^∗
Entrance to periphery (latency, s)	17.0±5.3	21.7±8	10.7±2.5	57.6±16.9^#	10.6±3.2^∗	7.8±2.8^∗
Vertical activity (latency, s)	49.2±6.9	75.0±14	119.7±31.2^∗	87.5±17.7	29.5±5.3^#∗	34.2±6.4^#∗
Self-grooming (latency, s)	173.0±57.0	172.3±18	172.1±18.3	127.8±11.6	136.9±23.5	183.0±21.0
Total self-grooming duration (s)	3.2±1.6	3.9±1.0	6.7±1.3^∗	4.4±0.9	5.6±1.0	3.0±0.9
Defecation boli (𝑛)	2.0±0.3	2.7±0.7	2.8±0.4	3.2±0.5	4.4±0.5	2.9±0.6
Dark-light box test
Latency to enter into the lit area (s)	16.2±2.4	25.5±5.9	47.4±28.2	39.4±12.3	11.5±2.3^∗	16.1±5.9
Defecation boli (𝑛)	0.2±0.2	4.3±0.7^∗	4.2±0.5^∗	2.4±0.4	4.0±1.3	4.4±0.7
Morris water maze tasks
Place learning task
Mean speed on day 1 (cm/s)	18.9±0.8	21.6±0.9	20.9±0.7	19.3±0.8	22.7±0.7	22.7±1.2
Mean speed on day 2 (cm/s)	20.6±0.6	23.4±1.2	22.7±0.7	19.4±1.1	23.8±0.7	24.0±1.3
Mean speed on day 3 (cm/s)	22.0±0.5	21.4±1.6	23.7±0.7	19.2±1.5	23.3±0.3	23.3±1.4
Mean speed on day 4 (cm/s)	21.7±1.2	20.9±0.8	19.9±1.1	18.0±2.0	23.3±0.7	23.4±1.3
Mean speed (cm/s)	20.8±0.7	21.8±1.0	21.8±0.6	19.0±1.1^#	23.2±0.4^∗	23.4±1.2^∗
Probe trial
Annulus crossings (𝑛)	8.0±1.41	8.4±1.5	10.1±1.0	5.6±0.8	6.3±1.1	6.9±0.7
Cue learning task
Mean distance covered (cm)	567.0±62.5	138.2±42.4	399.7±149.9	235.9±71.0^#	312.8±162.6	293.7±96.6
Mean speed (cm/s)	19.1±0.5	19.3±1.3	20.4±0.7	14.8±1.6^#p	18.8±1.1^p	19.0±1.4^p
T-maze
Performance (latency, s)	8.7±1.2	12.9±1.7	11.3±1.3	20.0±5.9^#	9.9±1.2^∗	7.8±1.0^∗

Note: non-Tg, nontransgenic mice; TgSED, 3xTgAD mice not exercised; TgEXE, 3xTg-AD mice submitted to a daily treadmill running for five weeks. The 3xTg-AD mice exhibited several behavioral changes indicative of increased neofobia, emotionality, anxiety-like behavior, hyperactivity, and impulsivity, which were mainly observed in females. The exercise did not induce major changes but showed gender-dependent effects. Results are the mean ± SEM, 𝑛=8-10 as indicated. Statistics: ^∗𝑃<.05 compared to non-Tg;^#𝑃<.01 compared to TgSED, pcompared to mean speed on place learning task 𝑃<.05.