Salt intake reduction using umami substance-incorporated food: a secondary analysis of NHANES 2017-2018 data.

OBJECTIVE: Excessive salt intake raises blood pressure and increases the risk of non-communicable diseases (NCD), such as CVD, chronic kidney disease and stomach cancer. Reducing the Na content of food is an important public health measure to control the NCD. This study quantifies the amount of salt reduced by using umami substances, i.e. glutamate, inosinate and guanylate, for adults in the USA. DESIGN: The secondary data analysis was performed using data of the US nationally representative cross-sectional dietary survey, the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Per capita daily salt intake corresponding to the NHANES food groups was calculated in the four hypothetical scenarios of 0 %, 30 %, 60 % and 90 % market share of low-Na foods in the country. The salt reduction rates by using umami substances were estimated based on the previous study results. SETTING: The USA. PARTICIPANTS: 4139 individuals aged 20 years and older in the USA. RESULTS: Replacing salt with umami substances could help the US adults reduce salt intake by 7·31-13·53 % (7·50-13·61 % for women and 7·18-13·53 % for men), which is equivalent to 0·61-1·13 g/d (0·54-0·98 g/d for women and 0·69-1·30 g/d for men) without compromising the taste. Approximately, 21·21-26·04 % of the US adults could keep their salt intake below 5 g/d, the WHO's recommendation in the scenario where there is no low-Na product on the market. CONCLUSIONS: This study provides essential information that the use of umami substances as a substitute for salt may help reduce the US adults' salt intake.

TrkB Signaling in Dorsal Raphe Nucleus is Essential for Antidepressant Efficacy and Normal Aggression Behavior.

Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB), have important roles in neural plasticity and are required for antidepressant efficacy. Studies examining the role of BDNF-TrkB signaling in depression and antidepressant efficacy have largely focused on the limbic system, leaving it unclear whether this signaling is important in other brain regions. BDNF and TrkB are both highly expressed in the dorsal raphe nucleus (DRN), a brain region that has been suggested to have a role in depression and antidepressant action, although it is unknown whether BDNF and TrkB in the dorsal raphe nucleus are involved in these processes. We combined the adeno-associated virus (AAV) with the Cre-loxP site-specific recombination system to selectively knock down either Bdnf or TrkB in the DRN. These mice were then characterized in several behavioral paradigms including measures of depression-related behavior and antidepressant efficacy. We show that knockdown of TrkB, but not Bdnf, in the DRN results in loss of antidepressant efficacy and increased aggression-related behavior. We also show that knockdown of TrkB or Bdnf in this brain region does not have an impact on weight, activity levels, anxiety, or depression-related behaviors. These data reveal a critical role for TrkB signaling in the DRN in mediating antidepressant responses and normal aggression behavior. The results also suggest a non-cell autonomous role for BDNF in the DRN in mediating antidepressant efficacy.

Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in neural plasticity in the adult nervous system and has been suggested as a target gene for antidepressant treatment. The neurotrophic hypothesis of depression suggests that loss of BDNF from the hippocampus contributes to an increased vulnerability for depression, whereas upregulation of BDNF in the hippocampus is suggested to mediate antidepressant efficacy. METHODS: We have used a viral-mediated gene transfer approach to assess the role of BDNF in subregions of the hippocampus in a broad array of behavioral paradigms, including depression-like behavior and antidepressant responses. We have combined the adeno-associated virus (AAV) with the Cre/loxP site-specific recombination system to induce the knockout of BDNF selectively in either the CA1 or dentate gyrus (DG) subregions of the hippocampus. RESULTS: We show that the loss of BDNF in either the CA1 or the DG of the hippocampus does not alter locomotor activity, anxiety-like behavior, fear conditioning, or depression-related behaviors. However, the selective loss of BDNF in the DG but not the CA1 region attenuates the actions of desipramine and citalopram in the forced swim test. CONCLUSIONS: These data suggest that the loss of hippocampal BDNF per se is not sufficient to mediate depression-like behavior. However, these results support the view that BDNF in the DG might be essential in mediating the therapeutic effect of antidepressants.

Caffeine regulates neuronal expression of the dopamine 2 receptor gene.

The psychoactive drug caffeine influences neuronal physiology; however, it is unknown whether it can dynamically alter the expression of genes that influence neurotransmission. Here, we report that caffeine stimulates transcription of the dopamine 2 receptor (D2R) gene in PC-12 cells and primary striatal cultures and increases D2R protein expression in the striatum. Physiological doses of caffeine and the specific adenosine 2A receptor antagonist 8-(3-chlorostyryl) caffeine both increased the activity of a D2R/luciferase reporter construct within 24 h, and simultaneous treatment with 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680), a specific adenosine 2A receptor agonist, eliminated this effect. Tests of additional constructs revealed that specific regions of the D2R promoter (-117/-75) and 5'-untranslated region (+22/+317) were required for activation of D2R gene expression by caffeine. In primary striatal cultures, caffeine increased spontaneous firing of neurons between 12 and 80 min after treatment, whereas it increased D2R mRNA expression after only 4 h. These results indicate that regulation of D2R gene expression by caffeine occurs after the initial physiological response has subsided. In vivo, female mice treated with a dose of caffeine (50 mg/kg) showed 1.94- and 2.07-fold increases in D2R mRNA and protein expression, respectively. In contrast, male mice exhibited a 31% decrease in D2R mRNA expression and showed no changes in D2R protein expression. Collectively, these results demonstrate for the first time that caffeine alters D2R expression in neurons. They also suggest that caffeine consumption can lead to sexually dimorphic patterns of gene expression in the brain.

The paired-like homeodomain protein, Arix, mediates protein kinase A-stimulated dopamine beta-hydroxylase gene transcription through its phosphorylation status.

The homeodomain transcription factor Arix/Phox2a plays a critical role in the specification of noradrenergic neurons by inducing the expression of dopamine beta-hydroxylase (DBH), the terminal enzyme for noradrenaline biosynthesis. In reporter assays, Arix together with activation of cAMP-dependent protein kinase (PKA) potentiates DBH gene transcription. We have evaluated whether post-translational modification of Arix regulates PKA-mediated DBH gene transcription. We found that Arix is constitutively phosphorylated in vivo at the basal level and that the phosphorylation level is substantially decreased upon stimulation of the PKA pathway. The change in the Arix phosphorylation state coincides with DNA binding activity of Arix. Treatment of cells with forskolin results in a robust enhancement of the DNA binding of Arix, which is reversed by treatment with serine/threonine and tyrosine phosphatase inhibitors. Consistent with the DNA binding activity of Arix, treatment of cultured cells with phosphatase inhibitors diminishes transcriptional activation with Arix plus forskolin. Amino acid analysis demonstrates the presence of phosphoserine within Arix. The results collectively suggest that dephosphorylation of Arix is a necessary event to fully activate PKA-mediated DBH transcription. Thus, the present study demonstrates that Arix can integrate extrinsic signals through post-translational modification, regulating DBH gene transcription in response to activation of the PKA pathway.