Heat stroke alters hippocampal and cerebellar transmitter metabonomics

doi:10.5847/wjem.j.1920-8642.2023.068

Abstract

Abstract:

BACKGROUND: The mechanisms underlying heat stroke (HS)-induced hippocampal injury remain unclear. This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.
METHODS: The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42 °C at a humidity of (55.0±5.0)%. The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The primary transmitters and metabolites were identified by principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). The major metabolic pathways for HS were selected after enrichment. The brain injury was evaluated by histological tests.
RESULTS: HS induced hippocampal and cerebellar injuries in rats. HS upregulated the protein levels of hippocampal glutamate, glutamine, gamma-aminobutyric acid, L-tryptophan (Trp), 5-hydroxy-indoleacetic acid, and kynurenine; however, it downregulated asparagine, tryptamine, 5-hydroxytryptophan, melatonin, 3,4-dihydroxyphenylalanine (L-DOPA), and vanillylmandelic acid. HS also sharply elevated the protein levels of cerebellar methionine and Trp, and decreased the levels of serotonin, L-alanine, L-asparagine, L-aspartate, cysteine, norepinephrine, spermine, spermidine, and tyrosine. Hippocampal glutamate, monoamine transmitters, cerebellar aspartate acid, and catecholamine transmitters’ metabolic pathways were identified as the main metablic pathways in HS.
CONCLUSION: The hippocampus and cerebellum were injured in rats with HS, possibly induced the disorder of hippocampal glutamate and serotonin metabolism, cerebellar aspartate acid and catecholamine transmitter metabolism, and related metabolic pathways.

Key words: Heat stroke, Transmitters, Rat, Hippocampus, Cerebellum, Metabonomics

Guoxin He, Ancong Xu, Xichong Yu, Fan Huang, Lei Su. Heat stroke alters hippocampal and cerebellar transmitter metabonomics[J]. World Journal of Emergency Medicine, 2023, 14(4): 287-293.

Figures/Tables 4

Figure 1.

Table 1.

Table 2.

Figure 2.

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Compound name	VIP	P-value	Fold change	Regulation
L-glutamic acid (Glu)	1.391410350	<0.05	1.371534	↑
L-glutamine (Gln)	1.681899013	<0.001	1.606678	↑
L-asparagine (Asn)	1.457180395	<0.05	0.787333	↓
4-aminobutyric acid (GABA)	1.372936595	<0.01	1.459465	↑
Acetylcholine chloride (Ach)	1.400312818	<0.01	0.529971	↓
5-hydroxyindoleacetic acid (5-HIAA)	1.384964116	<0.01	1.448424	↑
Kynurenine (Kyn)	1.754754057	<0.01	3.483045	↑
Tryptamine (TrpA)	1.385057321	<0.05	0.132325	↓
L-tryptophan (Trp)	1.334111293	<0.05	1.764086	↑
5-hydroxytryptophan (5-HTP)	1.111993357	<0.05	0.653240	↓
Melatonin (Mela)	1.225034363	<0.01	0.245155	↓
3,4-dihydroxyphenylalanine (L-DOPA)	1.576011841	<0.05	0.244428	↓
Vanillylmandelic acid (VMA)	1.678857063	<0.01	0.001838	↓
Methionine	1.269673747	<0.01	1.724238	↑
L-valine	1.046323137	<0.05	1.497150	↑

Compound name	VIP	P-value	Fold change	Regulation
5-hydroxytryptophan (5-HTP)	1.557076558	<0.01	0.457304	↓
L-asparagine (Asn)	1.384797285	<0.01	0.797578	↓
L-aspartate (Asp)	1.557810988	<0.01	0.791039	↓
L-cysteine (Cys)	1.238163380	<0.05	0.777153	↓
3-hydroxytyramine hydrochloride (DA)	1.327901546	<0.05	0.531398	↓
Methionine	1.420488814	<0.01	2.014877	↑
Norepinephrine (NE)	1.177455390	<0.05	0.640569	↓
Serine	1.394655013	<0.01	0.797151	↓
Spermidine	1.591320591	<0.001	0.656303	↓
Spermine	1.896975546	<0.001	0.436674	↓
L-tryptophan (Trp)	1.103058659	<0.05	1.598324	↑
L-alanine	1.522088412	<0.01	0.700086	↓
L-tyrosine	1.152037262	<0.05	0.760573	↓

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