bims-medebr 2021-12-05 papers

Issue of 2021‒12‒05
five papers selected by
Regina F. Fernández
Johns Hopkins University

Neurosci Lett. 2021 Nov 27. pii: S0304-3940(21)00742-4. [Epub ahead of print]768 136363

Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors.

Milica Jankovic, Natasa Spasojevic, Harisa Ferizovic, Bojana Stefanovic, Sladjana Dronjak.

An increasing body of evidence shows significant sex differences in the mammalian brain in multiple behaviours and psychiatric and neurological diseases and as well as that the endocannabinoid system may differ between males and females. In this study we investigated sex differences in working, short-term and long-term memory and the expression of β2-adrenergic and D1- and D2-receptors in the mPFC and hippocampus, brain regions that are involved in stress response and memory modulation in rats exposed to the chronic unpredictable stress (CUS) and the potential beneficial effects of the chronic fatty acid amide hydrolase inhibitor URB597 treatment. Chronically stressed male rats had an improvement of working memory, while stressed females showed very low object-recognition abilities. On the other hand, animals of both sexes exhibited long-term memory impairment. Our results showed that CUS decreased the expression of β2-adrenoceptors in the mPFC and D1 receptors in the mPFC and hippocampus of male rats and decreased β2-adrenoceptors and D1- receptors in the hippocampus of female. URB597 treatment had a positive effect on the short-term memory of stressed animals of both sexes whereas failed to restore long-term memory and did not affect the protein levels β2-adrenoceptors and D1 receptors in the hippocampus of CUS female rats. The present results support that endocannabinoids induced long-term memory and neurochemical alternations which are sex dependent, suggesting sex specific treatment strategies of mental disorders.

Keywords: Catecholamines; Depression; Endocannabinoid system; Memory; Receptors; Sex differences

DOI: https://doi.org/10.1016/j.neulet.2021.136363

Mol Cell Endocrinol. 2021 Nov 26. pii: S0303-7207(21)00366-X. [Epub ahead of print] 111522

Lipid endocannabinoids in energy metabolism, stress and developmental programming.

Mariana Macedo Almeida, Camilla Pereira Dias-Rocha, Camila Calviño Moraes, Isis Hara Trevenzoli.

The endocannabinoid system (ECS) regulates brain development and function, energy metabolism and stress in a sex-, age- and tissue-dependent manner. The ECS comprises mainly the bioactive lipid ligands anandamide (AEA) and 2-aracdonoylglycerol (2-AG), cannabinoid receptors 1 and 2 (CB1 and CB2), and several metabolizing enzymes. The endocannabinoid tonus is increased in obesity, stimulating food intake and a preference for fat, reward, and lipid accumulation in peripheral tissues, as well as favoring a positive energy balance. Energy balance and stress responses share adaptive mechanisms regulated by the ECS that seem to underlie the complex relationship between feeding and emotional behavior. The ECS is also a key regulator of development. Environmental insults (diet, toxicants, and stress) in critical periods of developmental plasticity, such as gestation, lactation and adolescence, alter the ECS and may predispose individuals to the development of chronic diseases and behavioral changes in the long term. This review is focused on the ECS and the developmental origins of health and disease (DOHaD).

Keywords: Developmental plasticity; Endocannabinoids; Epigenetics; Obesity; Sex differences; Stress

DOI: https://doi.org/10.1016/j.mce.2021.111522

Neuroscience. 2021 Nov 26. pii: S0306-4522(21)00602-3. [Epub ahead of print]

Lactate supply from astrocytes to neurons and its role in ischemic stroke-induced neurodegeneration.

Kazuo Yamagata.

Glucose transported to the brain is metabolized to lactate in astrocytes and supplied to neuronal cells via a monocarboxylic acid transporter (MCT). Lactate is used in neuronal cells for various functions, including learning and memory formation. Furthermore, lactate can block stroke-induced neurodegeneration. We aimed to clarify the effect of astrocyte-produced lactate on stroke-induced neurodegeneration. Previously published in vivo and in vitro animal and cell studies, respectively, were searched in PubMed, ScienceDirect, and Web of Science. Under physiological conditions, lactate production and release by astrocytes are regulated by changes in lactate dehydrogenase (LDH) and MCT expression. Moreover, considering stroke, lactate production and supply are regulated through hypoxia-inducible factor (HIF)-1α expression, especially with hypoxic stimulation, which may promote neuronal apoptosis; contrastingly, neuronal survival may be promoted via HIF-1α. Stroke stimulation could prevent neurodegeneration through the strong enhancement of lactate production, as well as upregulation of MCT4 expression to accelerate lactate supply. However, studies using astrocytes derived from animal stroke models revealed significantly reduced lactate production and MCT expression. These findings suggest that the lack of lactate supply may strongly contribute to hypoxia-induced neurodegeneration. Furthermore, diminished lactate supply from astrocytes could facilitate stroke-induced neurodegeneration. Therefore, astrocyte-derived lactate may contribute to stroke prevention.

Keywords: astrocytes; glutamate; ischemic stroke; lactic acid; monocarboxylic acid transporter; neurodegeneration

DOI: https://doi.org/10.1016/j.neuroscience.2021.11.035

Sci Rep. 2021 Nov 29. 11(1): 23104

Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats.

Yukari Shida, Hitoshi Endo, Satoshi Owada, Yutaka Inagaki, Hideaki Sumiyoshi, Akihide Kamiya, Tomoo Eto, Masayuki Tatemichi.

To fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required. THA rats established by crossing those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.

DOI: https://doi.org/10.1038/s41598-021-02591-7

Biol Trace Elem Res. 2021 Dec 02.

Study on the Effect of Different Iodine Intake on Hippocampal Metabolism in Offspring Rats.

Li Zhang, Lijun Fan, Fan Li, Qihao Sun, Yao Chen, Yanhong He, Hongmei Shen, Lixiang Liu.

Iodine is an essential trace element in the human body. Severe maternal iodine deficiency during pregnancy leads to obvious intellectual disability in the offspring. The effects of iodine deficiency on brain development have been demonstrated, but there is no clear evidence of the effects of iodine excess on brain development. To clarify the effects of iodine excess on the brain development of offspring and to provide clues to the mechanisms underlying the effects of iodine deficiency and iodine excess on the brain development of offspring. In this study, animal models with different iodine intakes were constructed using potassium iodate (KIO3). The models included four experimental groups (low-iodine group one (LI, 0μg/L iodine), low-iodine group two (LII, 5μg/L iodine), high-iodine group one (HI, 3000μg/L iodine), and high-iodine group two (HII, 10000μg/L iodine)) and one control group (NI, 100μg/L iodine). There were 20 female rats in each group, and 8 offspring were chosen from each group following birth to assess metabolic alterations. The metabolites of subsets of brain hippocampal tissue were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and the results were subjected to multivariate data analysis. Differential substances were screened by t test (p<0.05), principal component analysis (PCA), and partial least squares analysis (PLS-DA, VIP>1). The thyroid function of the female rats in the experimental group was abnormally changed. Metabolic analysis showed that the five groups were separated which revealed significant differences in hippocampal tissue metabolism among the five groups of offspring. A total of 12 potential metabolites were identified, with the majority of them being related to amino acid and energy metabolism. These metabolites are involved in various metabolic pathways, are interrelated, and may play a function in brain development. Our study highlights changes in metabolites and metabolic pathways in the brain hippocampus of offspring rats with different iodine intakes compared to controls, revealing new insights into hippocampal metabolism in offspring rats and new relevant targets.

Keywords: Hippocampus; Iodine deficiency; Iodine excess; Metabolomics; Offspring brain development

DOI: https://doi.org/10.1007/s12011-021-03032-2