Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids

Hermes, Douglas J.; Jacobs, Ian R.; Key, Megan C.; League, Alexis F.; Yadav-Samudrala, Barkha J.; Xu, Changqing; McLane, Virginia D.; Nass, Sara R.; Jiang, Wei; Meeker, Rick B.; Ignatowska-Jankowska, Bogna M.; Lichtman, Aron H.; Li, Zibo; Wu, Zhanhong; Yuan, Hong; Knapp, Pamela E.; Hauser, Kurt F.; Fitting, Sylvia

doi:10.1186/s12974-020-01971-6

Journal of Neuroinflammation

Table 5 Effects of Tat and morphine on levels of eCB and other lipid signaling molecules (pg/mg) in the striatum and spinal cord of Tat transgenic mice that were not significantly altered by Tat and/or morphine for any of the two CNS regions

From: Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids

CNS region	Lipids	Genotype	Repeated saline	Repeated morphine	Genotype effect		Drug effect		Genotype x drug
CNS region	pg/mg		mean ± SEM	mean ± SEM	F_{1, 13}	p	F_{1, 13}	p	F_{1, 13}	p
Striatum	2-AG	Tat(−)	11879.7 ± 1270.52	15441.7 ± 2440.16	< 1.0	0.93	2.1	0.17	< 1.0	0.52
	2-AG	Tat(+)	13140.9 ± 2086.96	14476.7 ± 1229.29	< 1.0	0.93	2.1	0.17	< 1.0	0.52
	AEA	Tat(−)	8.4 ± 0.52	9.1 ± 1.87	2.3	0.15	< 1.0	0.47	2.3	0.15
	AEA	Tat(+)	8.4 ± 1.08	6.4 ± 0.33	2.3	0.15	< 1.0	0.47	2.3	0.15
	NAGly	Tat(−)	16.0 ± 1.18	17.0 ± 1.26	< 1.0	0.47	1.0	0.33	< 1.0	0.85
	NAGly	Tat(+)	16.7 ± 1.55	18.10 ± 0.62	< 1.0	0.47	1.0	0.33	< 1.0	0.85
	POEA	Tat(−)	4.9 ± 0.34	5.9 ± 0.93	1.1	0.31	< 1.0	0.36	1.5	0.24
	POEA	Tat(+)	5.0 ± 0.23	4.8 ± 0.39	1.1	0.31	< 1.0	0.36	1.5	0.24
	LEA	Tat(−)	6.0 ± 0.74	7.9 ± 1.71	< 1.0	0.46	< 1.0	0.96	3.2	0.10
	LEA	Tat(+)	7.1 ± 1.33	5.2 ± 0.67	< 1.0	0.46	< 1.0	0.96	3.2	0.10
	DEA	Tat(−)	2.8 ± 0.09	3.6 ± 0.91	< 1.0	0.39	1.1	0.32	1.7	0.22
	DEA	Tat(+)	2.9 ± 0.20	2.8 ± 0.16	< 1.0	0.39	1.1	0.32	1.7	0.22
	DHEa	Tat(−)	16.1 ± 0.64	18.1 ± 4.25	< 1.0	0.66	< 1.0	0.58	2.9	0.11
	DHEa	Tat(+)	18.4 ± 1.99	14.3 ± 0.61	< 1.0	0.66	< 1.0	0.58	2.9	0.11
Spinal cord	2-AG	Tat(−)	11168.1 ± 1849.25	13770.4 ± 4148.01	1.4	0.26	1.4	0.26	< 1.0	0.90
	2-AG	Tat(+)	9033.6 ± 993.83	11126.1 ± 1239.95	1.4	0.26	1.4	0.26	< 1.0	0.90
	AEA	Tat(−)	5.8 ± 0.79	5.7 ± 2.03	< 1.0	0.77	< 1.0	0.60	< 1.0	0.55
	AEA	Tat(+)	5.3 ± 0.48	7.1 ± 1.98	< 1.0	0.77	< 1.0	0.60	< 1.0	0.55
	NAGly	Tat(−)	22.8 ± 2.07	22.3 ± 4.38	< 1.0	0.43	< 1.0	0.74	< 1.0	0.56
	NAGly	Tat(+)	19.6 ± 1.81	21.7 ± 1.19	< 1.0	0.43	< 1.0	0.74	< 1.0	0.56
	POEA	Tat(−)	8.7 ± 3.12	4.9 ± 0.58	< 1.0	0.83	< 1.0	0.71	< 1.0	0.38
	POEA	Tat(+)	6.7 ± 2.02	8.3 ± 3.38	< 1.0	0.83	< 1.0	0.71	< 1.0	0.38
	LEA	Tat(−)	10.6 ± 4.75	5.7 ± 1.40	< 1.0	0.66	< 1.0	0.78	< 1.0	0.52
	LEA	Tat(+)	9.5 ± 3.85	11.4 ± 6.26	< 1.0	0.66	< 1.0	0.78	< 1.0	0.52
	DEA	Tat(−)	3.9 ± 0.30	3.8 ± 1.19	< 1.0	0.82	< 1.0	0.37	1.1	0.32
	DEA	Tat(+)	3.2 ± 0.42	4.3 ± 0.57	< 1.0	0.82	< 1.0	0.37	1.1	0.32
	DHEa	Tat(−)	15.8 ± 0.55	18.4 ± 6.49	< 1.0	0.61	1.5	0.24	< 1.0	0.48
	DHEa	Tat(+)	14.7 ± 1.02	24.9 ± 7.59	< 1.0	0.61	1.5	0.24	< 1.0	0.48

Levels of eCB and non-eCB lipids in the striatum and spinal cord of repeated (8-day) saline- or morphine-treated Tat(−) and Tat(+) mice were not significantly affected by Tat and/or morphine for any of the two CNS regions. Data are expressed as mean ± SEM in pg/mg. Two-way ANOVAs for each CNS region were conducted with genotype and drug as between-subjects factors. F values and p values are presented from ANOVA results. n = 3–5 mice per group. All significant effects are represented in Fig. 7

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