Active coping with stress suppresses glucose metabolism in the rat hypothalamus

Figures & data

Figure 1.  Representative transverse slices showing glucose uptake in the head of rats that chewed a wooden stick during IMO stress (a) without or (b) with the pretreatment injection of botulinum toxin type A into the temporalis muscle (indicated by arrows to the right side). Intensity of SUV is shown in a pseudocolor scaling using MIPAV software package (red-to-blue indicates high-to-low accumulation of glucose, respectively). Note the clear picture of the brain of the chewing rat after blocking of the temporalis muscle in (b).

Figure 2.  Time-course changes of plasma corticosterone concentration in the rats that were immobilized with (SC) and without (ST) chewing (n = 4 each). Blood was collected from the tail vein three times at 24 h before IMO (Baseline), immediately after IMO for 30 min, and 1 h after the end of IMO. Asterisk indicates a statistically significant difference (P < 0.05) for values obtained at different points in time for the same condition. Dagger indicates a statistically significant difference (P < 0.05) between values obtained for two different conditions at corresponding points in time. The one-way ANOVA test and the post hoc Tukey's multiple comparison with Bonferroni correction were used to determine significant differences.

Figure 3.  Transverse slices shown from caudal (left) to rostral (right), indicating brain area with significant difference for the relative value of glucose uptake for each pair of conditions. Red and blue color indicate significantly increased and decreased glucose uptake in the former condition compared with that in the latter one, respectively (P values < 0.01; uncorrected). The statistical differences were determined by SPM using a general linear-model approach with proportional normalization and grand mean scaling. Bregma was set to the point of origin in the caudal-rostral axis according to the anatomical atlas of the rat brain (Paxinos and Watson 2007). Arrows indicate the position of the hypothalamus. CT, control (no IMO); ST, rats under IMO without chewing; SC, rats under IMO with chewing; n = 6 each.

Table I.  Ratio of glucose uptake in subregions of the hypothalamus to total glucose uptake in the brain (10^{− 2}%).

			CT	SC	ST	F(2,10)	P
PVN	Hypothalamic paraventricular nucleus		7.42 ± 0.09	7.61 ± 0.10	8.00 ± 0.13*,^†	12.99	0.005
SPa	Subparaventricular zone of the hypothalamus		1.38 ± 0.02	1.41 ± 0.02	1.51 ± 0.03*,^†	16.18	0.001
AH	Anterior hypothalamic area	R	3.99 ± 0.05	4.16 ± 0.08	4.48 ± 0.12*,^†	18.76	0.001
		L	4.13 ± 0.04	4.27 ± 0.05	4.59 ± 0.06*,^†	12.07	0.002
Arc	Hypothalamic arcuate nucleus		3.25 ± 0.05	3.56 ± 0.11	3.91 ± 0.11*	11.73	0.017
JPLH	Juxtaparaventricular part of lateral hypothalamus	R	0.64 ± 0.01	0.64 ± 0.01	0.66 ± 0.01*	4.26	0.046
		L	0.64 ± 0.01	0.65 ± 0.01	0.68 ± 0.01*	4.66	0.037
PLH	Peduncular part of lateral hypothalamus	R	17.05 ± 0.15	17.82 ± 0.15*	18.47 ± 0.25*	27.85	0.001
		L	17.10 ± 0.22	18.49 ± 0.16*	18.67 ± 0.19*	16.93	0.001
TuLH	Tuberal region of lateral hypothalamus	R	4.02 ± 0.07	4.45 ± 0.06*	4.70 ± 0.13*	16.25	0.001
		L	4.10 ± 0.08	4.54 ± 0.04*	4.76 ± 0.10*	16.16	0.001
PeFLH	Perifornical part of lateral hypothalamus	R	4.19 ± 0.06	4.35 ± 0.07	4.60 ± 0.06*,^†	8.75	0.006
		L	4.19 ± 0.07	4.48 ± 0.08	4.63 ± 0.07*	15.31	0.009
VMH	Hypothalamic ventromedial nucleus	R	4.56 ± 0.07	4.94 ± 0.13	5.37 ± 0.16*	10.99	0.017
		L	4.59 ± 0.08	4.96 ± 0.08	5.37 ± 0.14*	12.1	0.016
DMH	Hypothalamic dorsomedial nucleus	R	2.12 ± 0.03	2.20 ± 0.06	2.32 ± 0.04*	8.17	0.008
		L	2.12 ± 0.03	2.21 ± 0.04	2.32 ± 0.05*	8.73	0.006
PH	Posterior hypothalamic area	R	4.99 ± 0.06	5.05 ± 0.09	5.13 ± 0.05	1.66	0.239
		L	5.92 ± 0.05	6.08 ± 0.08	6.05 ± 0.06	1.94	0.194

Note: All values shown are mean ± SE of the mean. CT, control (no IMO); SC, immobilized with chewing; ST, immobilized without chewing; n = 6 each

*Significantly larger than CT (P < 0.05)

^† Significantly larger than SC (P < 0.05); post hoc Tukey's multiple comparison with Bonferroni correction after one-way ANOVA.

Figure 4.  Transverse slices shown from caudal (left) to rostral (right), indicating the difference in distribution of relative glucose uptake in the hypothalamus for the three experimental conditions: (a) voxel-based and (b) ROI-based statistical comparisons. CT, control (no IMO); ST, rats under IMO without chewing; SC, rats under IMO with chewing; n = 6 each. AH, anterior hypothalamic area; Arc, arcuate hypothalamic nucleus; DMH, dorsomedial hypothalamic nucleus; PeFLH, perifornical part of lateral hypothalamus; PH, posterior hypothalamic area; PLH, posterior lateral hypothalamus; PVN, paraventricular nucleus; TuLH, tuberal region of lateral hypothalamus; VMH, ventromedial hypothalamic nucleus. Red: significant increase in ST and SC compared with CT. Yellow, significant increase in ST compared with CT; Green, significant difference between each pair of conditions, where ST is the highest and followed by SC and CT; Cyan, significant increase in ST compared with SC and CT. One-way ANOVA and post hoc Tukey's multiple comparison with Bonferroni correction were used to determine statistical differences.

Table II.  Effect of paralysis of the temporalis muscle on the regional glucose uptake in the brain.

	Coordinates (mm)
Condition	x	y	z	Maximum T value	Activated area
CT	Intact>paralyzed
	1.4	1.6	− 4.6	2.87	Striatum
	− 2.4	1.4	− 1.6	3.09	Secondary motor cortex
	1.2	− 1.2	− 1.8	2.96
	− 4.2	− 3.0	− 5.4	3.34	Internal capsule
	− 5.4	− 3.4	− 2.6	3.42	Primary somatosensory cortex, barrel field
	5.0	− 3.6	− 3.0	3.12
	Paralyzed > intact
	− 1.2	− 1.2	− 6.2	4.65	Anteromedial thalamic nucleus
	2.0	− 1.6	− 6.6	3.37	Ventral anterior thalamic nucleus
	0.0	− 1.8	− 8.2	3.41	Hypothalamic paraventricular nucleus
	4.8	− 5.8	− 7.2	3.49	Hippocampus
	− 5.4	− 6.0	− 3.8	3.37
	2.2	− 6.2	− 4.6	5.04	Superior colliculus
	− 1.4	− 7.8	− 3.4	6.65
	0.2	− 7.2	− 6.6	4.98	Dorsal raphe nucleus
	0.4	− 12.2	− 1.6	3.75	Cerebellum
ST	Intact > paralyzed
	2.2	− 9.8	− 3.8	3.24	Cerebellum
	Paralyzed > intact
	− 2.4	− 8.4	− 2.6	3.30	Retrosplenial granular cortex

Note: Coordinates indicates the position with maximum T value in the activated area and directly correspond to the Paxinos coordinate system (Paxinos and Watson 2007). CT, control (no IMO); ST, immobilized without chewing; n = 6 each. Significant differences were determined between rats with their temporalis muscle intact and paralyzed using a general linear-model approach with proportional normalization and grand mean scaling by SPM (P values < 0.01; uncorrected).

Table III.  Effect of order of three experimental conditions on the regional glucose uptake in the brain.

	Coordinates (mm)
Condition	x	y	z	Maximum T value	Activated area
CT	Naïve > prior experience (conditions ST and SC)
	− 1.2	5.0	− 5.2	7.82	Orbital cortex
	3.0	4.2	− 3.4	7.80	Primary motor cortex
	2.4	0.2	− 9.2	4.59	Islands of Calleja
	3.6	− 1.8	− 9.2	5.77	Amygdala
	− 4.4	− 12.8	− 3.6	4.33	Cerebellum
	− 1.4	− 15.4	− 8.2	5.43	Medullary reticular nucleus
	Prior experience (conditions ST and SC) > Naïve
	− 0.6	1.6	− 5.8	5.15	Lateral septal nucleus
	− 1.8	1.2	− 1.2	4.02	Primary/Secondary motor cortex
	1.6	0.0	− 0.8	3.81
	1.4	− 7.0	− 1.4	5.98	Retrosplenial dysgranular cortex
	− 2.6	− 9.4	− 4.2	8.28	Cerebellum
SC	Naïve > prior experience (conditions CT and ST)
	− 4.2	3.8	− 3.6	5.54	Primary motor cortex
	2.8	3.6	− 3.0	6.06
	4.6	1.8	− 5.2	8.21	Primary somatosensory cortex
	− 6.2	− 0.2	− 6.2	4.34	Insular, secondary somatosensory cortex
	5.6	− 0.8	− 6.2	8.27
	4.4	− 1.0	− 8.2	6.40	Dorsal endopiriform nucleus
	1.8	− 3.6	− 6.0	11.02	Posterior thalamic nucleus
	− 2.0	− 4.0	− 7.6	11.11	Peduncular part of lateral hypothalamus
	0.8	− 4.2	− 8.2	7.17
	− 1.8	− 4.8	− 7.6	8.61	Prerubral field
	0.0	− 6.0	− 7.0	12.61	Medial accessory oculomotor nucleus
	− 1.6	− 7.0	− 3.6	8.34	Superior colliculus
	− 2.6	− 13.4	− 3.2	7.58	Cerebellum
	3.6	− 14.0	− 5.2	4.56
	Prior experience (conditions CT and ST) > Naïve
	2.2	2.4	− 8.4	8.57	Olfactory tubercle
	− 2.6	2.0	− 8.2	5.20
	− 3.4	− 2.8	− 4.0	5.38	Hippocampus
	0.6	− 3.0	− 4.4	3.73
	− 0.6	− 4.2	− 4.8	5.25	Habenular nucleus
	1.4	− 9.4	− 3.6	5.24	Cerebellum
ST	Naïve > prior experience (conditions CT and SC)
	− 0.4	0.0	− 7.8	3.94	Medial preoptic area
	1.0	− 1.2	− 6.4	4.04	Anteromedial thalamic nucleus
	− 5.0	− 4.6	− 7.4	5.95	Hippocampus
	− 1.6	− 7.0	− 3.6	8.32	Superior colliculus
	1.0	− 7.0	− 3.0	6.67
	0.2	− 7.6	− 7.2	10.60	Dorsal raphe nucleus
	1.2	− 8.8	− 7.4	6.01	Dorsomedial tegmental area
	1.4	− 10.6	− 7.4	3.86	Medial vestibular nucleus
	− 1.6	− 10.6	− 7.8	7.70
	− 2.4	− 11.8	− 5.8	4.39	Cerebellum
	Prior experience (conditions CT and SC) > Naïve
	3.0	4.2	− 3.4	5.40	Primary motor cortex
	− 5.4	2.6	− 5.4	4.35	Insular cortex
	4.6	1.8	− 5.2	5.51	Primary somatosensory cortex
	4.2	0.4	− 7.6	4.12	Dorsal endopiriform nucleus
	5.8	− 2.6	− 8.2	4.02	Piriform cortex

Note: Coordinates indicates the position with maximum T value in the activated area and directly correspond to the Paxinos coordinate system (Paxinos and Watson 2007). CT, control (no IMO); SC, immobilized with chewing; ST, immobilized without chewing; n = 2 each. Significant differences were determined between rats that experienced the condition for the first scan (Naïve) and those for the third scan (Prior experience), using a general linear-model approach with proportional normalization and grand mean scaling (P values < 0.01; uncorrected).

Paxinos G, Watson C. 2007. The rat brain in stereotaxic coordinates. Amsterdam: Elsevier.

 Google Scholar