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Middle-aged females are resistant to LPS-induced learning deficits: Sex comparison.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-01-10 Epub Date: 2024-12-04 DOI: 10.1016/j.neulet.2024.138072
Lauren G Singleton, Kelsey F Thompson, Jordyn Carroll, Rachel A Kohman
{"title":"Middle-aged females are resistant to LPS-induced learning deficits: Sex comparison.","authors":"Lauren G Singleton, Kelsey F Thompson, Jordyn Carroll, Rachel A Kohman","doi":"10.1016/j.neulet.2024.138072","DOIUrl":"10.1016/j.neulet.2024.138072","url":null,"abstract":"<p><p>Preclinical data have repeatedly shown learning and memory disruption following administration of the bacterial endotoxin lipopolysaccharide (LPS). Normal aging is reported to enhance vulnerability to LPS-induced cognitive impairments. However, a limitation is the primary use of male subjects. Recent evidence indicates sex-related differences in vulnerability to LPS-induced cognitive deficits [1,2], with young females showing resilience. Whether middle-aged females are susceptible to LPS-induced cognitive impairment is unknown. The current experiment compared associative learning in young and middle-aged male and female C57BL/6J mice following a systemic LPS challenge. While LPS impaired acquisition of the two-way active avoidance conditioning task in adult and middle-aged males, females' learning was unaffected. The sex difference in LPS-induced cognitive impairments appears unrelated to responsivity to LPS, as males and females mount a comparable sickness-like response. Additionally, relative to males, females produce higher brain levels of interleukin-6 (IL-6) and comparable splenic IL-6 levels following LPS. These data demonstrate that female resilience to LPS-induced learning deficits persists into middle age, whereas males are vulnerable as both young and middle-aged adults. Our findings confirm the importance of considering sex as a biological variable and extend the existing literature by evaluating sex-related responsivity to LPS in middle-aged males and females.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"138072"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the antinociceptive effect of taraxasterol in mice: Possible mechanisms.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-01-10 Epub Date: 2024-12-03 DOI: 10.1016/j.neulet.2024.138075
Cagil Onal Sis, Yagmur Okcay, Kemal Gokhan Ulusoy, Ismail Mert Vural, Oguzhan Yıldız
{"title":"Exploring the antinociceptive effect of taraxasterol in mice: Possible mechanisms.","authors":"Cagil Onal Sis, Yagmur Okcay, Kemal Gokhan Ulusoy, Ismail Mert Vural, Oguzhan Yıldız","doi":"10.1016/j.neulet.2024.138075","DOIUrl":"10.1016/j.neulet.2024.138075","url":null,"abstract":"<p><strong>Objectives: </strong>Taraxasterol is the active ingredient of Taraxacum officinale which has been used in traditional medicine for its several therapeutic effects. This study aims first to evaluate the potential spinal/supraspinal and peripheral/visceral antinociceptive effect of taraxasterol and then to investigate the contribution of GABAergic, opioidergic systems, and K<sub>ATP</sub> channels to its antinociceptive effect.</p><p><strong>Methods: </strong>The antinociceptive activity of taraxasterol (2.5, 5, and 10 mg/kg i.p.) was investigated with hot-plate, tail-immersion, and acetic acid-induced abdominal writhing tests (for supraspinal, spinal, peripheral/visceral pain evaluation, respectively) in BALB/c male mice, and percentage of possible maximum effect (MPE%) values were calculated. Mechanism of action studies were performed by pre-administering bicuculline, naloxone, and glibenclamide.</p><p><strong>Results: </strong>Taraxasterol increased the MPE% values in hot-plate and tail-immersion tests at 2.5, 5, and 10 mg/kg doses (P < 0.001) and decreased the mean number of writhes at 10 mg/kg in the abdominal writhing test (P < 0.05). Naloxone and bicuculline pre-administration reversed the antinociceptive effect of taraxasterol in hot-plate and tail-immersion tests and it had no effect in the abdominal writhing test. Pre-administration of glibenclamide reversed the antinociceptive effect of taraxasterol in all tests.</p><p><strong>Conclusion: </strong>Our study is the first to show the involvement of GABAergic and opioidergic systems in the antinociceptive effect of taraxasterol in supraspinal and spinal pain tests, and K<sub>ATP</sub> channels in tests evaluating supraspinal, spinal, and peripheral pain pathways. Taraxasterol is a potential new herbal medicine that can be used for pain control.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138075"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-panic effect of fluoxetine during late diestrus in female rats is mediated through GABAergic mechanisms in the dorsal periaqueductal gray.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-01-10 Epub Date: 2024-12-05 DOI: 10.1016/j.neulet.2024.138078
Matheus F Batistela, Paloma M Hernandes, Alana T Frias, Thelma A Lovick, Helio Zangrossi
{"title":"Anti-panic effect of fluoxetine during late diestrus in female rats is mediated through GABAergic mechanisms in the dorsal periaqueductal gray.","authors":"Matheus F Batistela, Paloma M Hernandes, Alana T Frias, Thelma A Lovick, Helio Zangrossi","doi":"10.1016/j.neulet.2024.138078","DOIUrl":"10.1016/j.neulet.2024.138078","url":null,"abstract":"<p><p>Panic disorder is more frequent in women than in men. In women, vulnerability to panic is enhanced during the late luteal phase of the menstrual cycle. At this time secretion of progesterone and its neuroactive metabolite allopregnanolone (ALLO), which acts as a positive allosteric modulator of the actions of GABA at GABA<sub>A</sub> receptors, decline sharply. In female rats, responsiveness to a hypoxic panicogenic challenge increases during the late diestrus (LD) phase as ALLO concentration in the brain falls. During LD, short-term treatment with fluoxetine at a low dose (1.75 mg/kg i.p.) blocked panic-related escape behavior in response to hypoxia. At this dose fluoxetine increases brain concentration of ALLO without affecting 5-HT levels, thereby stabilizing brain ALLO concentration. We here report that the panicolytic-like effect of fluoxetine during LD is prevented by microinjection of the GABA<sub>A</sub> receptor antagonist bicuculline (5 pmol) into the dorsal periaqueductal gray (dPAG), a key panic-related area. This result suggests that fluoxetine's effect is indirectly mediated via a GABAergic mechanism in the dPAG and highlights the important role of changes in GABAergic tone in regulating neuronal excitability in the panic circuitry during the estrous cycle. It also points to the potential for using short-term, low dose fluoxetine as an anti-panic medication in women.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138078"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Agmatine diminishes behavioral and endocrine alterations in a rat model of post-traumatic stress disorder.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-01-10 Epub Date: 2024-12-05 DOI: 10.1016/j.neulet.2024.138074
Mayur B Kale, Sandip R Rahangdale, Trupti A Banarase, Mohd Shahnavaj Siddiqui, Brijesh G Taksande, Manish M Aglawe, Aman B Upaganlawar, Spandana Rajendra Kopalli, Sushruta Koppula, Milind J Umekar, Nitu L Wankhede
{"title":"Agmatine diminishes behavioral and endocrine alterations in a rat model of post-traumatic stress disorder.","authors":"Mayur B Kale, Sandip R Rahangdale, Trupti A Banarase, Mohd Shahnavaj Siddiqui, Brijesh G Taksande, Manish M Aglawe, Aman B Upaganlawar, Spandana Rajendra Kopalli, Sushruta Koppula, Milind J Umekar, Nitu L Wankhede","doi":"10.1016/j.neulet.2024.138074","DOIUrl":"10.1016/j.neulet.2024.138074","url":null,"abstract":"<p><p>Post-traumatic stress disorder (PTSD), is a severe anxiety disorder characterized by associative fear conditioning. Single prolonged stress (SPS) is a widely accepted reliable animal model to stimulate PTSD. Agmatine is an endogenous neuromodulator of stress; however, its effect on PTSD remains to be investigated. This study explored the role of agmatine in conditioned fear response (CFR) in PTSD and highlighted the role of imidazoline receptors in the effect of agmatine. Intra-cerebroventricular (icv) surgery was done in order to facilitate drug administration. Animals were subjected to SPS. Agmatine and the involvement of imidazoline receptors (I<sub>1</sub> and I<sub>2</sub>) were assessed for their effect in fear conditioning apparatus. During weeks 1, 2, and 3, in CFR, agmatine (40 µg/rat, icv) showed significantly decreased freezing time whereas other doses of agmatine (10 and 20 µg/rat, icv). Imidazoline (I<sub>1</sub> and I<sub>2</sub>) receptor agonists Moxonidine (25 µg/rat, icv) and 2-BFI, (10 µg/rat, icv) respectively, at their sub-effective doses, with a submaximal dose of agmatine (20 µg/rat, icv) significantly decreased the altered freezing time during weeks 1, 2 and 3 compared to SPS animals. Moreover, the effective dose of agmatine (40 µg/rat, icv) with imidazoline (I<sub>1</sub> and I<sub>2</sub>) receptor antagonists Efaroxan (10 µg/rat, icv) and Idazoxan (4 µg/rat, icv) respectively does not reversed the effect of agmatine on freezing. Agmatine and its combination with I<sub>1</sub> and I<sub>2</sub> agonists, normalized the altered freezing behavior, corticosterone level, organ coefficient of adrenal gland, neuroinflammatory and neurotrophic factor due to SPS during CFR projecting its strong therapeutic effect in SPS induced PTSD.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138074"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preventive and therapeutic effects of genistein and daidzein on anxiety-like behaviors in ovariectomized rats.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-01-10 Epub Date: 2024-12-06 DOI: 10.1016/j.neulet.2024.138073
Sarinee Kalandakanond-Thongsong, Suwaporn Daendee, Sushawadee Tongta, Boonrit Thongsong, Anan Srikiatkhachorn
{"title":"Preventive and therapeutic effects of genistein and daidzein on anxiety-like behaviors in ovariectomized rats.","authors":"Sarinee Kalandakanond-Thongsong, Suwaporn Daendee, Sushawadee Tongta, Boonrit Thongsong, Anan Srikiatkhachorn","doi":"10.1016/j.neulet.2024.138073","DOIUrl":"10.1016/j.neulet.2024.138073","url":null,"abstract":"<p><p>Estrogen has demonstrated beneficial effects; however, it can also have unfavorable effects. Phytoestrogens are present in many consumable products and commonly used as supplements. These are of interest as they may have beneficial effects on mood with fewer undesirable effects on reproductive tissues. This study investigated the anxiolytic-like effects of the phytoestrogens genistein and daidzein on ovariectomized (Ovx) rats and their effects on the expression of uterine estrogen receptors (ER) and brain monoamines. In experiment 1, Ovx rats received either vehicle, 17β-estradiol, or 0.25 - 1 mg/kg of genistein or daidzein for 4 weeks before behavioral tests of anxiety. In experiment 2, we assessed the therapeutic effects of genistein and daidzein. The ovariectomies were used to induce anxiety, so the treatments were started 3 weeks post-ovariectomy. The Ovx rats received vehicle, 17β-estradiol, or 0.25 mg/kg of genistein or daidzein daily for 4 weeks before behavioral tests. We found daidzein and genistein comparable to 17β-estradiol in their anxiolytic-like effects. Further, while 17β-estradiol decreased body weight gain, increased uterine weight, and increased the uterine ERα/ERβ ratio, neither genistein nor daidzein had these undesirable effects. The alterations in brain monoamines following genistein or daidzein treatments were somewhat different from those seen after 17β-estradiol treatment. In conclusion, daily daidzein or genistein administration for 4 weeks did not negatively affect body weight, food intake, uterine tissue, uterine ER expressions, or ERα/ERβ ratio but demonstrated anxiolytic-like effects on Ovx rats. We conclude that low-dose (0.25 mg/kg) genistein or daidzein can alleviate anxiety in a female anxious rat model.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138073"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex related differences in cognitive deficits: Disrupted Arc/Arg3.1 signaling in an HIV model.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-01-10 Epub Date: 2024-11-29 DOI: 10.1016/j.neulet.2024.138071
Yun-Kyung Hahn, Sara R Nass, William D Marks, Jason J Paris, Kurt F Hauser, Pamela E Knapp
{"title":"Sex related differences in cognitive deficits: Disrupted Arc/Arg3.1 signaling in an HIV model.","authors":"Yun-Kyung Hahn, Sara R Nass, William D Marks, Jason J Paris, Kurt F Hauser, Pamela E Knapp","doi":"10.1016/j.neulet.2024.138071","DOIUrl":"10.1016/j.neulet.2024.138071","url":null,"abstract":"<p><p>Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased. We utilized a transgenic mouse model of HIV that conditionally expresses HIV-1 Tat<sub>1-86</sub> in the CNS to examine cognitive behaviors and the expression of biomarkers related to learning and memory in both sexes. Tat+ males exhibited deficits in spatial learning/memory and object recognition, while Tat+ females showed enhanced fear memory. We investigated the involvement of activity-regulated cytoskeleton-associated protein (Arc), which is induced by novel experience related to learning/memory. We observed hippocampal Arc induction following foot shock in Tat+ females but not Tat+ males. Hippocampal levels of Arc, amyloid β (Aβ) monomers/oligomers and pCREB were altered in a sex-specific manner. CREB activity, which is highly associated with Arc induction, was reduced only in Tat+ males. Tat exposure also decreased Arc expression in cultured human neurons. Thus, HIV-1 Tat effects on CREB/Arc signaling may differ between sexes, contributing to differences in cognitive deficits observed here and in PLWH.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138071"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute astrocytic and neuronal regulation of glutamatergic protein expression following blast.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2024-12-27 DOI: 10.1016/j.neulet.2024.138108
Carly Norris, Susan F Murphy, Pamela J VandeVord
{"title":"Acute astrocytic and neuronal regulation of glutamatergic protein expression following blast.","authors":"Carly Norris, Susan F Murphy, Pamela J VandeVord","doi":"10.1016/j.neulet.2024.138108","DOIUrl":"https://doi.org/10.1016/j.neulet.2024.138108","url":null,"abstract":"<p><p>Regulation of glutamate through glutamate-glutamine cycling is critical for mediating nervous system plasticity. Blast-induced traumatic brain injury (bTBI) has been linked to glutamate-dependent excitotoxicity, which may be potentiating chronic disorders such as post-traumatic epilepsy. The purpose of this study was to measure changes in the expression of astrocytic and neuronal proteins responsible for glutamatergic regulation at 4-, 12-, and 24 h in the cortex and hippocampus following single blast exposure in a rat model for bTBI. Animals were exposed to a blast with magnitudes ranging from 16 to 20 psi using an Advanced Blast Simulator, and western blotting was performed to compare changes in protein expression between blast and sham groups. Glial fibrillary acidic protein (GFAP) was increased at 24 h, consistent with astrocyte reactivity, yet no other proteins showed significant changes in expression at acute time points following blast (GS, GLT-1, GluN1, GluN2A, GluN2B). Therefore, these glutamate regulators likely do not play a major role in contributing to acute excitotoxicity or glial reactivity when analyzed by whole brain region. Investigation of substructural and subregional effects in future studies, particularly within the hippocampus (e.g., dentate gyrus, CA1, CA2, CA3), may reveal localized changes in expression and/or NMDAR subunit composition capable of potentiating bTBI molecular cascades. Nevertheless, alternative regulators are likely to demonstrate greater sensitivity as acute therapeutic targets contributing to bTBI pathophysiology following single blast exposure.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138108"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ondansetron blocks fluoxetine effects in immature neurons in the adult rat piriform cortex layer II.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2024-12-26 DOI: 10.1016/j.neulet.2024.138099
Marina Recatalá, Pablo Hidalgo, Juan Nàcher, José Miguel Blasco-Ibáñez, Carlos Crespo, Emilio Varea
{"title":"Ondansetron blocks fluoxetine effects in immature neurons in the adult rat piriform cortex layer II.","authors":"Marina Recatalá, Pablo Hidalgo, Juan Nàcher, José Miguel Blasco-Ibáñez, Carlos Crespo, Emilio Varea","doi":"10.1016/j.neulet.2024.138099","DOIUrl":"https://doi.org/10.1016/j.neulet.2024.138099","url":null,"abstract":"<p><p>Neuronal structural plasticity gives the adult brain the capacity to adapt to internal or external factors by structural and molecular changes. These plastic processes seem to be mediated, among others, by the action of the neurotransmitter serotonin through specific receptors (5-HTRs). Previous studies have shown that the maturation of granule cells in the hippocampus is mediated by 5-HT3. In the present study, we wanted to check if the neural maturation in layer II piriform cortex is also mediated by 5-HT3. In the piriform cortex, in contrast to the hippocampus, there is no postnatal neurogenesis. All immature neurons (PSA-NCAM immunoreactive) were originated prenatally. Immature cells in this area begin as small cells (type I cells) that then mature to larger cells (type II cells), and finally, mature to principal cells (PSA-NCAM immunonegative). To study the role of 5HT3 in this population, we first demonstrated the presence of 5HT3 receptors on both type I and II cells. Then we increased serotonin concentration using chronic fluoxetine administration, producing a reduction in the number of type I cells and an increment of type II cells but not an induction in the final stage of maturation to principal cells, as shown by the higher number of immature cells than in controls. This effect was blocked by ondansetron (a 5 HT3 antagonist). In conclusion, serotonin induces the progression from type I cells to type II cells but not from the later to mature PSA-NCAM immunonegative neurons. This effect is mediated by 5-HT3 receptors present in the immature cells.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138099"},"PeriodicalIF":2.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Remimazolam alleviates sleep deprivation induced anxiety-like behaviors via regulating the STING pathway.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2024-12-25 DOI: 10.1016/j.neulet.2024.138095
Jun Fan, Jumian Feng, Lin Yang, Qin Zhang, Huaqiu Li
{"title":"Remimazolam alleviates sleep deprivation induced anxiety-like behaviors via regulating the STING pathway.","authors":"Jun Fan, Jumian Feng, Lin Yang, Qin Zhang, Huaqiu Li","doi":"10.1016/j.neulet.2024.138095","DOIUrl":"10.1016/j.neulet.2024.138095","url":null,"abstract":"<p><p>Sleep loss becomes a major problem in modern life and increases the incidence of anxiety disorders. Benzodiazepines are the most commonly used anxiolytic medications. Remimazolam is an ultra-short-acting benzodiazepine, which has been shown to reduce the preoperative anxiety levels in patients. However, the effects on anxiety-like behaviors caused by chronic sleep deprivation (CSD) and the underlying molecular mechanisms remain unclear. Here, we found that administration of remimazolam can effectively alleviate anxiety-like behaviors induced by CSD. Furthermore, remimazolam can significantly preserve the sleep deprivation-induced deficits in neuronal calcium activity in CA1 of the hippocampus. In addition, stimulator of interferon genes (STING) was activated in CA1 after CSD, while remimazolam was sufficient to block the activation of the STING pathway. Further study showed that inhibiting the activation of STING also effectively alleviates the anxiety symptoms induced by CSD. Overall, our research offers new insight and a promising therapeutic agent for the anxiety disorders caused by sleep deprivation.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138095"},"PeriodicalIF":2.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The diagnostic value and molecular mechanisms of LncRNA ZFAS1 in neuropathic pain.
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2024-12-22 DOI: 10.1016/j.neulet.2024.138097
Yunchao Chu, Jing Chen, Huaqing Cui, Qiuyi Xie, Shasha Mei
{"title":"The diagnostic value and molecular mechanisms of LncRNA ZFAS1 in neuropathic pain.","authors":"Yunchao Chu, Jing Chen, Huaqing Cui, Qiuyi Xie, Shasha Mei","doi":"10.1016/j.neulet.2024.138097","DOIUrl":"10.1016/j.neulet.2024.138097","url":null,"abstract":"<p><strong>Objective: </strong>Long non-coding RNA (lncRNA) has been playing an increasingly significant role in neuropathic pain (NP). This study aimed to investigate the clinical significance and mechanism of LncRNA ZNFX1 antisense RNA 1 (ZFAS1) in NP.</p><p><strong>Methods: </strong>92 patients with NP and 85 healthy controls were enrolled, and a rat NP model was constructed by chronic constrictive injury (CCI). LPS-induced microglia BV2 cells were used to construct an in vitro cellular model. RT-qPCR analysis of the mRNA levels of ZFAS1, miR-421, and Iba-1 (markers of microglia activation). Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess mechanosensitive and thermal nociceptive allergic responses. ELISA assay for pro-inflammatory factors and anti-inflammatory factors expression. ROC assay for the diagnostic value of ZFAS1. Validation of the targeting between ZFAS1 and miR-421 by dual luciferase reporter assay.</p><p><strong>Results: </strong>ZFAS1 significantly increased while miR-421 significantly decreased in individuals with NP, in a rat model of CCI, and in LPS-induced microglial cells. Functionally, miR-421 directly targeted ZFAS1. ZFAS1 levels could significantly differentiate between NP patients and control (AUC = 0.910). Low expression of ZFAS1 significantly alleviated PWL and PWT in CCI rats. Elevated neuro-proinflammatory factors and decreased anti-inflammatory factors in CCI rats were significantly reversed by low expression of ZFAS1, but this is partially weakened by low expression of miR-421. Moreover, silencing ZFAS1 hindered the upregulation of Iba-1 expression induced by LPS, which was rescued significantly by miR-421.</p><p><strong>Conclusion: </strong>Elevated ZFAS1 is a potential bio-diagnostic marker for NP. Inhibition of ZFAS1 may alleviate NP progression by inhibiting microglia activation and neuro-inflammatory responses.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138097"},"PeriodicalIF":2.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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