Hinata Nishimura , Aurelien Kerever , Kana Kato , Tatsuki Ono , Shiomi Nakayama , Takahiro Tanaka , Ryusei Abe , Eri Arikawa-Hirasawa
{"title":"Oligodendrocyte differentiation on murine decellularized brain tissue","authors":"Hinata Nishimura , Aurelien Kerever , Kana Kato , Tatsuki Ono , Shiomi Nakayama , Takahiro Tanaka , Ryusei Abe , Eri Arikawa-Hirasawa","doi":"10.1016/j.neulet.2024.138079","DOIUrl":"10.1016/j.neulet.2024.138079","url":null,"abstract":"<div><div>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).</div><div>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 <em>in vitro</em> remains limited.</div><div>No methods have been elucidated for studying these short-lived and changeable cell populations using culture systems.</div><div>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 <em>in vivo</em>.</div><div>Herein, a culture system with decellularized brain tissue that retains organized ECM scaffolds was introduced to better mimic the <em>in vivo</em> 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.</div><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138079"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813840","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}
Samaneh Kakhki , Ali Abbaszade-Cheragheali , Seyyed Pouria Tafti , Atefeh Shirinzadeh Feizabadi , S. Mohammad Ahmadi-Soleimani , Farimah Beheshti
{"title":"Oral administration of crocin reverses memory loss induced by ethanol and nicotine abstinence in adolescent male rats","authors":"Samaneh Kakhki , Ali Abbaszade-Cheragheali , Seyyed Pouria Tafti , Atefeh Shirinzadeh Feizabadi , S. Mohammad Ahmadi-Soleimani , Farimah Beheshti","doi":"10.1016/j.neulet.2024.138077","DOIUrl":"10.1016/j.neulet.2024.138077","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138077"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812959","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}
Aidán Ortega , Antonio Laville , Montserrat Padilla-Orozco , Yohana Parrado , Dagoberto Tapia , Miguel Serrano-Reyes , Janintzitzic López-Niño , Héctor A. Vázquez-Vázquez , Elvira Galarraga , José Bargas
{"title":"Cortical beta oscillation in brain slices of hemi parkinsonian mice","authors":"Aidán Ortega , Antonio Laville , Montserrat Padilla-Orozco , Yohana Parrado , Dagoberto Tapia , Miguel Serrano-Reyes , Janintzitzic López-Niño , Héctor A. Vázquez-Vázquez , Elvira Galarraga , José Bargas","doi":"10.1016/j.neulet.2025.138128","DOIUrl":"10.1016/j.neulet.2025.138128","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor and non-motor symptoms. Beta oscillations in cortical areas are a pathognomonic sign. Here we ask whether these oscillations can be recorded in <em>in vitro</em> cortical tissue despite severing the cortico-basal ganglia-thalamo-cortical loop. M1/M2 cortex of hemi parkinsonian mice (6-OHDA) was recorded with multielectrode arrays (MEAs). Spectral decomposition analysis shows a significantly augmented beta band power with respect to controls. The administration of L-DOPA diminished this exacerbated beta rhythm. This result suggests that plastic changes induced by dopamine (DA) depletion remain in isolated cortical tissue even when the complete circuit is no longer present. This finding brings the opportunity to test anti-parkinsonian drugs <em>in vitro</em> by quantifying cortical beta band power.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138128"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008925","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}
Jesús Fernandez-Felipe , Lucía L. López , Victoria Cano , Enrique Sánchez-Hita , A. Belén Sanz , Julie A. Chowen , Nuria Del Olmo , Mariano Ruiz-Gayo , Beatriz Merino
{"title":"Corrigendum to “Regional specific effect of saturated vs unsaturated fat on leptin receptor signalling in mice brain areas regulating feeding” [Neurosci. Lett. 793 (2023) 136996, 1–5 doi.org/10.1016/j.neulet.2022.136996]","authors":"Jesús Fernandez-Felipe , Lucía L. López , Victoria Cano , Enrique Sánchez-Hita , A. Belén Sanz , Julie A. Chowen , Nuria Del Olmo , Mariano Ruiz-Gayo , Beatriz Merino","doi":"10.1016/j.neulet.2024.138076","DOIUrl":"10.1016/j.neulet.2024.138076","url":null,"abstract":"","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138076"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824456","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}
Qian Zhang , Jin Ke , Guangfu Cui , Shen Qian , Weixin Qian , Sun-Wook Moon , Yanyan Sun , Tianwen Huang , Zaisheng Qin
{"title":"The neural ensembles activated by propofol and isoflurane anesthesia across the whole mouse brain","authors":"Qian Zhang , Jin Ke , Guangfu Cui , Shen Qian , Weixin Qian , Sun-Wook Moon , Yanyan Sun , Tianwen Huang , Zaisheng Qin","doi":"10.1016/j.neulet.2024.138080","DOIUrl":"10.1016/j.neulet.2024.138080","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138080"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of galanin-like peptide on hypothalamic kisspeptin expression in female Zucker fatty rats","authors":"Akiko Sakata , Kinuyo Iwata , Kimihiko Nakao , Yuyu Kunimura , Shunji Suzuki , Hitoshi Ozawa , Hirotaka Ishii","doi":"10.1016/j.neulet.2024.138081","DOIUrl":"10.1016/j.neulet.2024.138081","url":null,"abstract":"<div><div>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 <em>Kiss1</em> cells and the proportion of <em>Fos</em>-positive <em>Kiss1</em> 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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138081"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138097"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","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}
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":"<div><div>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 <span><span>[1]</span></span>, <span><span>[2]</span></span>, 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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 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}
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":"<div><h3>Objectives</h3><div>Taraxasterol is the active ingredient of <em>Taraxacum officinale</em> 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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Taraxasterol increased the MPE% values in hot-plate and tail-immersion tests at 2.5, 5, and 10 mg/kg doses (<em>P</em> < 0.001) and decreased the mean number of writhes at 10 mg/kg in the abdominal writhing test (<em>P</em> < 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 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}
Matheus F. Batistela , Paloma M. Hernandes , Alana T. Frias , Thelma A. Lovick , Helio Zangrossi Jr
{"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 Jr","doi":"10.1016/j.neulet.2024.138078","DOIUrl":"10.1016/j.neulet.2024.138078","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 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}