Transcriptomic Changes of Astrocytes in the Brain of Rats with Subacute METH Exposure

doi:10.12116/j.issn.1004-5619.2021.310207

Abstract

Abstract: Objective

To study the transcriptomic changes of astrocytes in the brain of rats exposed to methamphetamine （METH） and its possible mechanism in neurotoxicity.

Methods

The rats were intraperitoneally injected with METH （15 mg/kg） every 12 h for 8 times in total to establish the subacute rat model of METH. After the model was successfully established, the striatum was extracted, and astrocytes were separated by the magnetic bead method. Transcriptome sequencing was performed on selected astrocytes, and the differentially expressed genes were analyzed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis.

Results

A total of 876 differentially expressed genes were obtained by transcriptome sequencing, including 321 up-regulated genes and 555 down-regulated genes. GO analysis revealed that differentially expressed genes were mainly concentrated in cell structure, biological process regulation, extracellular matrix and organelle functions. KEGG pathway enrichment analysis showed that steroids biosynthesis, fatty acid biosynthesis, peroxisome proliferators-activated receptor （PPAR）, adenosine 5’-monophosphate-activated protein kinase （AMPK） and other signaling pathways were significantly changed.

Conclusion

METH can cause structural changes of astrocytes through multiple targets, among which cellular structure, steroids biosynthesis and fatty acid biosynthesis may play an important role in nerve injury, providing a new idea for forensic identification of METH related death.

Key words: forensic toxicology, transcriptomics, methamphetamine, astrocyte, differentially expressed genes, signaling pathway

CLC Number:

DF795.1

Tao WANG, Sai-qun WU, Xiao-hui TAN, Chuan-xiang CHEN, Xia YUE, Hui-jun WANG, Si-hao DU, Dong-fang QIAO. Transcriptomic Changes of Astrocytes in the Brain of Rats with Subacute METH Exposure[J]. Journal of Forensic Medicine, 2021, 37(6): 806-812.

Figures/Tables 7

References 18

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样本	质控后序列数目	质控后测序总数据	错误率/%	Q20/%	Q30/%	GC含量/%
C1	54 415 668	8.10×10⁹	0.024 7	98.17	94.47	51.72
C2	53 003 362	7.89×10⁹	0.024 3	98.31	94.81	51.79
C3	5 1534 094	7.69×10⁹	0.024 5	98.25	94.66	51.52
M1	5 3065 998	7.93×10⁹	0.024 4	98.29	94.75	51.60
M2	4 9762 862	7.42×10⁹	0.024 3	98.30	94.78	51.40
M3	5 6424 684	8.42×10⁹	0.024 4	98.29	94.74	51.35

样本	质控后序列数目	质控后测序总数据	错误率/%	Q20/%	Q30/%	GC含量/%
C1	54 415 668	8.10×10⁹	0.024 7	98.17	94.47	51.72
C2	53 003 362	7.89×10⁹	0.024 3	98.31	94.81	51.79
C3	5 1534 094	7.69×10⁹	0.024 5	98.25	94.66	51.52
M1	5 3065 998	7.93×10⁹	0.024 4	98.29	94.75	51.60
M2	4 9762 862	7.42×10⁹	0.024 3	98.30	94.78	51.40
M3	5 6424 684	8.42×10⁹	0.024 4	98.29	94.74	51.35

基因	对照组			METH组			变化
基因	C1	C2	C3	M1	M2	M3	变化
Cpt1a	32.49	37.16	38.16	17.00	16.18	16.73	下调
Acsbg1	18.03	18.81	18.17	8.82	8.44	8.10	下调
Fabp5	76.32	83.56	81.43	616.29	618.12	633.62	上调
Scd2	238.24	245.37	256.20	1 826.88	1 788.51	1 898.72	上调
Scd	3.64	4.55	3.24	304.36	291.66	317.70	上调
Acsl3	11.03	9.11	10.55	39.12	43.06	43.89	上调
Gdf15	3.67	3.61	3.77	70.98	60.61	43.44	上调
Acsl4	6.60	5.86	6.36	17.10	19.35	19.63	上调
Acsl6	2.24	3.00	3.85	14.39	12.23	13.37	上调
Fabp3	10.84	11.75	10.27	24.22	23.91	24.37	上调

基因	对照组			METH组			变化
基因	C1	C2	C3	M1	M2	M3	变化
Cpt1a	32.49	37.16	38.16	17.00	16.18	16.73	下调
Acsbg1	18.03	18.81	18.17	8.82	8.44	8.10	下调
Fabp5	76.32	83.56	81.43	616.29	618.12	633.62	上调
Scd2	238.24	245.37	256.20	1 826.88	1 788.51	1 898.72	上调
Scd	3.64	4.55	3.24	304.36	291.66	317.70	上调
Acsl3	11.03	9.11	10.55	39.12	43.06	43.89	上调
Gdf15	3.67	3.61	3.77	70.98	60.61	43.44	上调
Acsl4	6.60	5.86	6.36	17.10	19.35	19.63	上调
Acsl6	2.24	3.00	3.85	14.39	12.23	13.37	上调
Fabp3	10.84	11.75	10.27	24.22	23.91	24.37	上调

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