Neuroscience Letters最新文献

Pain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic-pituitary-adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated. EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with Bacteroides, while aspartate uptake in the spinal cord positively correlated with the relative abundance of Lachnospiraceae NK4A136. Positive associations with aspartate uptake in the spinal cord were also observed for Alistipes and Bifidobacterium during oestrus, and Eubacterium coprostanoligenes during proestrus. Clostridium sensu stricto1 was negatively associated with aspartate uptake in the ACC in males and dioestrus females. These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.

Postoperative cognitive dysfunction (POCD) is a common cognitive challenge faced by older adults. One of the key contributors to the development of POCD is neuroinflammation induced by microglia. Resveratrol has emerged as a promising candidate for the prevention of cognitive decline. Previous studies have demonstrated its potential in alleviating cognitive deterioration, yielding encouraging results. Nonetheless, the mechanism of resveratrol improving cognitive function remains unclear. Therefore, we assessed the effect of resveratrol in both aged POCD model mice and BV2 cells on CX3CL1/CX3CR1 axis, a critical signaling pathway mediating microglial activity. Both in vitro and in vivo experiments have revealed that pre-administration of resveratrol not only mitigates cognitive deficits but also significantly reduces the levels of inflammatory cytokines. Additionally, it enhanced the expression of SIRT1 and CX3CR1 within the hippocampal region. We also evaluated the impact of resveratrol on CX3CR1 siRNA transfected BV2 cells. Delete of CX3CR1 reversed the preventive role of resveratrol. Our findings implied that resveratrol might inhibit microglial activation and improve cognition by mediating CX3CL1/CX3CR1 signaling.

This study established an animal model of comorbid depression and insomnia by combining chronic unpredictable mild stress (CUMS) with sleep deprivation (SD). The pathogenesis of comorbid depression and insomnia may be associated with impaired AMPK/FOXO3a signaling, which mediates autophagy inhibition, leading to decreased pineal melatonin secretion. The findings revealed that CUMS + SD rats exhibited more pronounced depression-like behaviors, sleep disorders, increased central oxidative stress, and exacerbated neuroinflammation, accompanied by reduced levels of 5-hydroxytryptophan (5-HT) and melatonin in the pineal gland. Notably, further investigations revealed that impaired mitochondrial autophagy in the pineal gland is closely linked to the significant suppression of AMPK/FOXO3a signaling. The combined intervention of venlafaxine and melatonin effectively ameliorated the impaired mitochondrial autophagy in the pineal gland of CUMS + SD rats and stimulated melatonin secretion. Consequently, the study proposes that dysfunctional mitochondrial autophagy regulated by the AMPK/FOXO3a pathway can influence melatonin secretion, thereby playing a pivotal role in the pathogenesis of depression combined with insomnia.

Rats which experienced neonatal bladder inflammation (NBI) have been demonstrated to exhibit latent bladder hypersensitivity with a nociceptive component that becomes unmasked by a second inflammatory insult as an adult. Manifested as augmented reflex and neuronal responses to urinary bladder distension (UBD), these NBI-induced changes are revealed by using inflammation of nearby structures as an adult pretreatment. The effect of inflammation in distant structures is not known. These studies examined visceromotor reflex responses and lumbosacral spinal dorsal horn neuronal responses to UBD in rats and compared effects of segmental (hindpaw) versus hetero-segmental (forepaw or face) inflammatory pretreatments in 192 female Sprague-Dawley rats raised from birth. On postnatal days 14-16 these rats underwent either NBI or control procedures. As adults, these rats received control injections or 0.1 ml Complete Freund's Adjuvant (CFA) injections into one of four sites. Three days later they were studied in reflex or spinal single-cell neuronal experiments where responses were evoked by UBD. Visceromotor responses to UBD were more robust in rats which had injections in the hindpaw (either side) but were not significantly affected by forepaw or facial injections. Similar results were identified in L6/S1 neurons with more robust UBD-evoked responses observed in rats receiving hindpaw CFA injections but not forepaw injections. These results indicate that latent bladder hypersensitivity induced by NBI is made manifest by segmental, but not hetero-segmental inflammatory stimuli. This observation correlates with pain in patients with interstitial cystitis who often have flares in symptoms associated with inflammation of nearby structures.

Kisspeptin and galanin-like peptide (GALP) neurons in the hypothalamic arcuate nucleus (ARC) are involved in gonadotropin-releasing hormone (GnRH) neuron-mediated pulsatile luteinizing hormone (LH) secretion. Zucker fatty (ZF) rats display a leptin receptor gene abnormality and suppressed pulsatile LH secretion. ZF rats reportedly exhibit low hypothalamic GALP and kisspeptin expression, and GALP administration induces LH release in ZF rats. Therefore, we performed a histochemical analysis to determine whether GALP-induced LH release is mediated by kisspeptin neurons in ZF rats. All ZF rats were ovariectomized and subcutaneously implanted with an estradiol tube before the central injection of GALP or vehicle. GALP administration increased the plasma LH concentration. However, no significant difference was observed in the number of Kiss1 cells and the proportion of Fos-positive Kiss1 cells. The number of c-Fos-positive GnRH neurons significantly increased after GALP administration. Our results suggest that hypothalamic GALP neurons promote LH release by activating GnRH neurons without the activation of kisspeptin neurons in the ARC.

Purpose: Regarding a wide variety of researches conducted with various therapeutic effect of crocin, the main constituent of saffron, the current study aims to assess the efficacy of crocin to improve learning and memory impairment caused by withdrawal following concurrent usage of ethanol (Eth) and nicotine (Nic) in adolescent male rats.

Methods: In order to test memory fucntion, Morris water maze and passive avoidance methods were applied in male Wistar rats undergone adolescent Nic-Eth withdrawal and the effect of crocin treatment was assessed at both behavioral and biochemical levels. The biochemical parameters included the inflammatory cytokines, indicators of oxidative stress and cholinergic metabolism within the hippocampla tissues. Animals were divided into 7 experimental groups as follows: 1) control (saline + saline), 2) nicotine + ethanol, 3-5) nicotine + ethanol + crocin (three doses), 6) nicotine + ethanol + bupropion + naloxone and 7) saline + crocin.

Results: Results indicated that crocin treatment effectively prevented the Nic-Eth withdrawal induced behavioral manifestations of memory impairment when assessed by Morris water maze and passive avoidance tests. In addition, the biochemical alterations (in inflammatory, oxidative and cholinergic parameters) induced by Nic-Eth withdrawal were also ameliorated in rats treated by crocin. Interestingly, the mentioned ameliorative effect of crocin was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration, when administered at high doses.

Conclusion: We would like to suggest the crocin treatment as an alternative medication for the management of Nic - Eth withdrawal, however, further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.

Loss of oligodendrocytes causes severe neurological damage. Oligodendrogenesis is the production of new oligodendrocytes throughout life and includes several developmental stages starting from oligodendrocyte precursor cells (OPCs). The GPR17-expressing cell population, an important intermediate stage in oligodendrocyte development, acts as a reservoir responding to brain injury and ischemia. GPR17 plays a complex role in oligodendrocyte maturation and response to injury; its activation promotes differentiation into more mature phenotypes. However, our understanding of GPR17-expressing oligodendrocytes in vitro remains limited. No methods have been elucidated for studying these short-lived and changeable cell populations using culture systems. The extracellular matrix (ECM) plays an important role in regulating the proliferation and differentiation of these cells; however, conventional two-dimensional culture systems cannot reproduce the complex structure and environmental conditions of the ECM in vivo. Herein, a culture system with decellularized brain tissue that retains organized ECM scaffolds was introduced to better mimic the in vivo environment. This system enabled the study of interactions between OPCs, ECM, and other cell types. Neurospheres containing progenitor cells that differentiate into oligodendrocyte lineage cells, neurons, and astrocytes were transplanted into decellularized brain slices. The results showed that this method not only promoted stem cell differentiation but also significantly enhanced differentiation into oligodendrocytes when supplemented with oligo buffer. This model system provides a better understanding of the interaction between OPCs and the ECM and a novel approach for studying the differentiation of GPR17-expressing cells, which may be useful for future therapeutic strategies for promoting remyelination and central nervous system repair.

General anesthesia has been widely used in surgical procedures. Propofol and isoflurane are the most commonly used injectable and inhaled anesthetics, respectively. The various adverse effects induced by propofol and isoflurane are highly associated with the anesthetic-dependent change of brain activities. In this work, we aim to delineate a brain-wide neuronal activity landscape of injectable versus inhaled anesthetics to understand the neural basis underlying the different physiological effects induced by these two major types of anesthetics. Through detailed scanning of the whole mouse brain subjected to propofol or isoflurane anesthesia, in total, we identified 17 subcortical regions, 3 of which (anterodorsal preoptic nucleus, ADP; lateral habenular, LHb; inferior olivary nucleus, ION) were specifically activated by propofol, and 3 (ventral part of the lateral septum, LSV; the intermediate part of the lateral septum, LSI; the solitary tract nucleus, Sol) were specifically activated by isoflurane, with the remaining 11 were activated by both two anesthetics. Moreover, within the 17 brain regions, ADP, SubCV (subcoeruleus nucleus, ventral part), PCRtA (parvicellular reticular nucleus, alpba part) and ION were newly identified that activated by propofol or isoflurane, respectively. By using Targeted Recombination in Active Populations (TRAP) technique, we further showed that propofol and isoflurane largely activate the same group of neurons in supraoptic nucleus (SON), but activate different groups of neurons in central amygdala (CeA). Our results reveals the neural ensembles activated by injectable and inhaled anesthetics, and provides detailed anatomical references for future studies on general anesthesia.