Sex-dimorphic moderate hypoglycemia preconditioning effects on Hippocampal CA1 neuron bio-energetic and anti-oxidant function

Uddin, Md. Main; Ibrahim, Mostafa M.H.; Aryal, Dinesh; Briski, Karen P.

doi:10.1007/s11010-020-03806-7

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Hippocampal neurons use glucose as their main source of energy. Changes in lipid levels in the central nervous system also affect the glucose metabolism of hippocampal neurons in brain areas responsible for learning and memory. − Lipids also play an important role in hippocampal neuron plasticity, learning, and memory . In this study, we found that the levels of ketogenic and glycogenic amino acids (tryptophan, phenylalanine, and tyrosine), lipid intake, and glucose utilization in the internal environment of 14 DIV neurons decreased.…”

Section: Discussionmentioning

confidence: 52%

Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy

et al. 2022

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Hippocampal neurons are sensitive to changes in the internal environment and play a significant role in controlling learning, memory, and emotions. A remarkable characteristic of the aging brain is its ability to shift from a state of normal inflammation to excessive inflammation. Various cognitive abilities of the elderly may suffer from serious harm due to the change in the neural environment. Hippocampal neurons may have various subsets involved in controlling their internal environment at different stages of development. Developmental differences may eventually result from complex changes in the dynamic neuronal system brought on by metabolic changes. In this study, we used an in vitro hippocampal neuron model cultured in C57BL/6J mice in conjugation with Raman spectroscopy to examine the relative alterations in potential biomarkers, such as levels of metabolites in the internal environment of hippocampal neurons at various developmental stages. The various differentially expressed genes (DEGs) of hippocampal neurons at various developmental stages were simultaneously screened using bioinformatics, and the biological functions as well as the various regulatory pathways of DEGs were preliminarily analyzed, providing an essential reference for investigating novel therapeutic approaches for diseases that cause cognitive impairment, such as Alzheimer’s disease. A stable hippocampal neuron model was established using the GIBCO C57BL/6J hippocampal neuron cell line as a donor and in vitro hippocampal neuron culture technology. The Raman peak intensities of culture supernatants from the experimental groups incubated for 0, 7, and 14 days in vitro(DIV) were examined. The GEO database was used to screen for different DEGs associated with various developmental stages. The data was then analyzed using a statistical method called orthogonal partial least squares discriminant analysis (OPLS-DA). The levels of ketogenic and glycogenic amino acids (such as tryptophan, phenylalanine, and tyrosine), lipid intake rate, glucose utilization rate, and nucleic acid expression in the internal environment of hippocampal neurons were significantly different in the 14 DIV group compared to the 0 DIV and 7 DIV groups ( P < 0.01). The top 10 DEGs with neuronal maturation were screened, and the results were compared to the OPLS-DA model’s analysis of the differential peaks. It was found that different genes involved in maturation can directly relate to changes in the body’s levels of ketogenic and glycogenic amino acids ( P < 0.01). The altered expression of the maturation-related genes epidermal growth factor receptor, protein tyrosine kinase 2-beta, discs large MAGUK scaffold protein 2, and Ras protein-specific guanine nucleotide releasing factor 1 may be connected to the altered uptake of ketogenic and glycogenic amino acids and nucleic acids in the internal environment of neurons at different developmental stages. The levels of ketogenic, glycogenic amino acids, and lipid intake ...

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Section: Discussionmentioning

confidence: 52%

Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy

et al. 2022

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Effect of β-Hydroxybutyrate on Autophagy Dynamics During Severe Hypoglycemia and the Hypoglycemic Coma

Torres-Esquivel

Montiel

Flores-Méndez

et al. 2020

Front. Cell. Neurosci.

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Glucose supply from blood is mandatory for brain functioning and its interruption during acute hypoglycemia or cerebral ischemia leads to brain injury. Alternative substrates to glucose such as the ketone bodies (KB), acetoacetate (AcAc), and β-hydroxybutyrate (BHB), can be used as energy fuels in the brain during hypoglycemia and prevent neuronal death, but the mechanisms involved are still not well understood. During glucose deprivation adaptive cell responses can be activated such as autophagy, a lysosomal-dependent degradation process, to support cell survival. However, impaired or excessive autophagy can lead to cell dysfunction. We have previously shown that impaired autophagy contributes to neuronal death induced by glucose deprivation in cortical neurons and that D isomer of BHB (D-BHB) reestablishes the autophagic flux increasing viability. Here, we aimed to investigate autophagy dynamics in the brain of rats subjected to severe hypoglycemia (SH) without glucose infusion (GI), severe hypoglycemia followed by GI (SH + GI), and a brief period of hypoglycemic coma followed by GI (Coma). The effect of D-BHB administration after the coma was also tested (Coma + BHB). The transformation of LC3-I to LC3-II and the abundance of autophagy proteins, Beclin 1 (BECN1), ATG7, and ATG12–ATG5 conjugate, were analyzed as an index of autophagosome formation, and the levels of sequestrosome1/p62 (SQSTM1/p62) were determined as a hallmark of autophagic degradation. Data suggest that autophagosomes accumulate in the cortex and the hippocampus of rats after SH, likely due to impaired autophagic degradation. In the cortex, autophagosome accumulation persisted at 6 h after GI in animals exposed to SH but recovered basal levels at 24 h, while in the hippocampus no significant effect was observed. In animals subjected to coma, autophagosome accumulation was observed at 24 h after GI in both regions. D-BHB treatment reduced LC3-II and SQSTM1/p62 content and reduced ULK1 phosphorylation by AMPK, suggesting it stimulates the autophagic flux and decreases AMPK activity reducing autophagy initiation. D-BHB also reduced the number of degenerating cells. Together, data suggest different autophagy dynamics after GI in rats subjected to SH or the hypoglycemic coma and support that D-BHB treatment can modulate autophagy dynamics favoring the autophagic flux.

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Sex-dimorphic moderate hypoglycemia preconditioning effects on Hippocampal CA1 neuron bio-energetic and anti-oxidant function

Cited by 2 publications

References 16 publications

Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy

Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy

Effect of β-Hydroxybutyrate on Autophagy Dynamics During Severe Hypoglycemia and the Hypoglycemic Coma

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