Abstract:
:Major depressive disorder is the leading cause of disability and suicidality worldwide. Here, we evaluated neural metabolic activity in prefrontal cortex (PFC) in C57BL6 mice undergoing a chronic unpredictable mild stress (CUMS) for three weeks to induce depression. Further, the efficacy of Lanicemine, a low trapping NMDA receptor antagonist, on behavioral and neurometabolic measures in CUMS mice was evaluated. The PFC neuronal and astroglial metabolic activity was evaluated by Proton Observed Carbon Edited (POCE) MR spectroscopy together with an infusion of [1,6-13C2]glucose and [2-13C]acetate, respectively. The rates of glutamatergic, GABAergic and astrocytic TCA cycles and neurotransmitter cycling were obtained by fitting a three-compartment metabolic model to 13C turnover of amino acids. Mice subjected to CUMS exhibited significantly reduced sucrose preference (CUMS 58.0 ± 12.5%, n = 29; Control 86.3 ± 6.4%, n = 30; p < 0.0001), and increased immobility (CUMS 146.1 ± 60.8s, n = 29; Control 29.9 ± 19.3s, n = 30; p < 0.0001) in the forced swim test. The concentrations of 13C labeled amino acids from [2-13C]acetate were decreased suggesting reduced astroglial metabolic activity in CUMS mice. The glutamatergic and GABAergic TCA cycle rates were decreased in CUMS mice when compared with controls. In addition, GABA-glutamine and glutamate-glutamine neurotransmitter cycling were reduced in mice subjected to CUMS regimen. Most interestingly, a short time intervention of lanicemine restored behavioral measures (sucrose preference and immobility), and rates of glucose oxidation in glutamatergic and GABAergic neurons in CUMS mice. In summary, our findings suggest that depression leads to a reduction in excitatory and inhibitory neurotransmission in PFC, and targeting glutamatergic pathway may have potential therapeutic role in chronic depression.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Mishra PK,Adusumilli M,Deolal P,Mason GF,Kumar A,Patel ABdoi
10.1016/j.neuint.2020.104750subject
Has Abstractpub_date
2020-07-01 00:00:00pages
104750eissn
0197-0186issn
1872-9754pii
S0197-0186(20)30141-8journal_volume
137pub_type
杂志文章abstract::The effects of membrane lipid disturbances induced by ischemia and exogenously added lipids on the uptake of GABA and Ca(2+) were investigated in gerbil brain synaptosomes. Ischemia was produced by bilateral ligation of common carotid arteries in Mongolian gerbil for 10 min. The level of the free fatty acids (FFA) inc...
journal_title:Neurochemistry international
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journal_title:Neurochemistry international
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journal_title:Neurochemistry international
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journal_title:Neurochemistry international
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journal_title:Neurochemistry international
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