Neuroscience
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Previous studies revealed that high long-term hypothalamic-pituitaryadrenal (HPA) axis activity measured by the hair cortisol concentrations predicts lower acute stress cortisol response and reported the influences of hair cortisol on brain activity during acute stress exposure. However, considering that long-term HPA axis activity has a close relationship with the brain's resting-state functional connectivity (RSFC), the current study aimed to explore the role of RSFC between limbic and salience network in this relationship. Seventy-seven healthy participants underwent resting-state imaging scans before performing the acute ScanSTRESS task. ⋯ Moreover, high HairE levels were significantly correlated with enhanced RSFC between limbic and salience networks, while RSFC was negatively associated with acute stress cortisol response. Importantly, the RSFC between left insula and left parahippocampus mediated the association between HairE and acute cortisol stress response. Taken together, this study uncovers the important role of RSFC between salience and limbic networks in the long-term relationship between HairE and acute cortisol response and contributes to a deeper understanding of the individual differences in acute stress response.
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Many threats activate parabrachial neurons expressing calcitonin gene-related peptide (CGRPPBN) which transmit alarm signals to forebrain regions. Most CGRPPBN neurons also express tachykinin 1 (Tac1), but there are also Tac1-expressing neurons in the PBN that do not express CGRP (Tac1+;CGRP- neurons). ⋯ Activating Tac1+;CGRP- neurons, using an intersectional genetic targeting approach, resembles activating all Tac1PBN neurons. These results reveal that activation of Tac1+;CGRP- neurons can suppress some functions attributed to the CGRPPBN neurons, which provides a mechanism to bias behavioral responses to threats.
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This study aimed to explore the neural mechanisms underlying food decision making in unsuccessful restrained eaters (US-REs) and successful restrained eaters (S-REs). During a functional magnetic resonance imaging scan, participants were required to choose between pairs of high- and low-calorie foods under the following conditions: the congruent condition (choose between high- and low-calorie foods with the same level of tastiness) and incongruent condition (choose between high-calorie foods tastier than the corresponding low-calorie foods). Subsequently, the participants' diets were monitored for one week. ⋯ Our results suggest that US-REs have a strong reward response to food. Compared to US-REs, S-REs are more guided more by the goal of weight control, and exhibit strong functional connections between the conflict-monitoring and inhibitory-control regions. Therefore, eating enjoyment and weight-control goals influence restrained eating in daily life.
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Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. ⋯ We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-β, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-β, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.
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Although the mechanisms underlying dystonia are largely unknown, dystonia is often associated with abnormal dopamine neurotransmission. DOPA-responsive dystonia (DRD) is a prototype disorder for understanding dopamine dysfunction in dystonia because it is caused by mutations in genes necessary for the synthesis of dopamine and alleviated by the indirect-acting dopamine agonist l-DOPA. Although adaptations in striatal dopamine receptor-mediated intracellular signaling have been studied extensively in models of Parkinson's disease, another movement disorders associated with dopamine deficiency, little is known about dopaminergic adaptations in dystonia. ⋯ The D2 dopamine receptor antagonist raclopride also significantly reduced the phosphorylation of ERK; this contrasts with models of parkinsonism in which l-DOPA-induced ERK phosphorylation is not mediated by D2 dopamine receptors. Further, the dysregulated signaling was dependent on striatal subdomains whereby ERK phosphorylation was largely confined to dorsomedial (associative) striatum while the dorsolateral (sensorimotor) striatum was unresponsive. This complex interaction between striatal functional domains and dysregulated dopamine-receptor mediated responses has not been observed in other models of dopamine deficiency, such as parkinsonism, suggesting that regional variation in dopamine-mediated neurotransmission may be a hallmark of dystonia.