Pub Date : 2024-11-01DOI: 10.1016/j.neulet.2024.138033
Effat Ramshini , Mohammad Shabani
Addiction can be viewed as a state of compulsive engagement in drug use. It is believed that drug-associated memories maintain compulsive drug-seeking behavior. Therefore, disrupting drug-associated memories may reduce drug-seeking behavior. In the present study, a conditioned place preference (CPP) apparatus was conducted to evaluate the effect of cannabinoid receptor type 1 (CB1R) agonist and antagonist on the acquisition of CPP induced by methamphetamine (METH). Anxiety behaviors and memory retrieval were assessed using elevated plus maze (EPM) and step-through passive avoidance tasks. In this study using a 5-day schedule of CPP, exposure to METH increased the time spent in the drug-paired compartment, and CB1Rs agonist (WIN 55,212–2, WIN) disrupted the METH-induced CPP. In the EPM experiment, METH significantly decreased the ratio of times spent in the open arms to total times spent in any arms (OAT) and the ratio of entries into open arms to total entries (OAE), indicating that METH increases anxiety-like behaviors. However, the CB1Rs antagonist (SR141716A, SR) reversed METH-induced anxiety behaviors. The results obtained in the passive avoidance experiment showed that blockade of brain CB1Rs by SR improves METH-induced amnesia. In summary, CB1Rs appear to modulate METH-associated memories, and antagonists of CB1Rs may serve as a therapeutic target for METH-induced anxiety behaviors.
{"title":"Cannabinoid receptor type 1 agonist disrupts methamphetamine-induced conditioned place preference in adolescent male rats","authors":"Effat Ramshini , Mohammad Shabani","doi":"10.1016/j.neulet.2024.138033","DOIUrl":"10.1016/j.neulet.2024.138033","url":null,"abstract":"<div><div>Addiction can be viewed as a state of compulsive engagement in drug use. It is believed that drug-associated memories maintain compulsive drug-seeking behavior. Therefore, disrupting drug-associated memories may reduce drug-seeking behavior. In the present study, a conditioned place preference (CPP) apparatus was conducted to evaluate the effect of cannabinoid receptor type 1 (CB1R) agonist and antagonist on the acquisition of CPP induced by methamphetamine (METH). Anxiety behaviors and memory retrieval were assessed using elevated plus maze (EPM) and step-through passive avoidance tasks. In this study using a 5-day schedule of CPP, exposure to METH increased the time spent in the drug-paired compartment, and CB1Rs agonist (WIN 55,212–2, WIN) disrupted the METH-induced CPP. In the EPM experiment, METH significantly decreased the ratio of times spent in the open arms to total times spent in any arms (OAT) and the ratio of entries into open arms to total entries (OAE), indicating that METH increases anxiety-like behaviors. However, the CB1Rs antagonist (SR141716A, SR) reversed METH-induced anxiety behaviors. The results obtained in the passive avoidance experiment showed that blockade of brain CB1Rs by SR improves METH-induced amnesia. In summary, CB1Rs appear to modulate METH-associated memories, and antagonists of CB1Rs may serve as a therapeutic target for METH-induced anxiety behaviors.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138033"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568627","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}
Diabetes mellitus is associated with cognitive deficits in humans and animal models. These deficits are paralleled by neurophysiological and structural changes in the central nervous system, particularly in the hippocampus, which plays an important role in memory formation. We previously reported that the magnitude of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses was significantly impaired in streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats). The present study investigated the mechanisms underlying morphological changes in the hippocampus of STZ rats. We performed a proteomic analysis of the hippocampus of STZ rats using two-dimensional gel electrophoresis followed by mass spectrometry. The distribution of 14–3-3 proteins identified by the proteomic analysis was then examined using immunohistochemistry. The results obtained revealed that 14–3-3 η immunoreactivity in the dorsal hippocampus was weaker in STZ rats than in age-matched control rats. Moreover, the density of glial fibrillary acidic protein-immunoreactive astrocytes in the dorsal hippocampus of STZ rats was increased, whereas 14–3-3 η immunoreactivity in astrocytes and neurons in the dentate gyrus was significantly decreased. These results suggest that changes in 14–3-3 η expression are involved in hippocampal astrogliosis or/and neurogenesis in STZ rats.
糖尿病与人类和动物模型的认知缺陷有关。这些缺陷与中枢神经系统，尤其是在记忆形成过程中起重要作用的海马体的神经生理学和结构变化同时发生。我们以前曾报道过，在链脲佐菌素（STZ）诱导的 1 型糖尿病大鼠（STZ 大鼠）中，海马沙弗侧索-CA1 突触的长期电位显著减弱。本研究探讨了 STZ 大鼠海马形态学变化的机制。我们采用二维凝胶电泳法和质谱法对 STZ 大鼠的海马进行了蛋白质组分析。然后使用免疫组织化学方法检测了蛋白质组分析所确定的 14-3-3 蛋白的分布。结果显示，STZ 大鼠海马背侧的 14-3-3 η 免疫反应弱于年龄匹配的对照组大鼠。此外，STZ 大鼠海马背侧神经胶质纤维酸性蛋白免疫反应性星形胶质细胞的密度增加，而齿状回中星形胶质细胞和神经元的 14-3-3 η 免疫反应性显著降低。这些结果表明，14-3-3 η表达的变化参与了STZ大鼠海马星形胶质细胞或/和神经发生。
{"title":"Isoform-specific distribution of 14–3-3 proteins in the hippocampus of streptozotocin-induced diabetic rats","authors":"Sachie Sasaki-Hamada , Arisa Hara , Yume Tainaka , Sho Satoh , Jun-Ichiro Oka , Hitoshi Ishibashi","doi":"10.1016/j.neulet.2024.138027","DOIUrl":"10.1016/j.neulet.2024.138027","url":null,"abstract":"<div><div>Diabetes mellitus is associated with cognitive deficits in humans and animal models. These deficits are paralleled by neurophysiological and structural changes in the central nervous system, particularly in the hippocampus, which plays an important role in memory formation. We previously reported that the magnitude of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses was significantly impaired in streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats). The present study investigated the mechanisms underlying morphological changes in the hippocampus of STZ rats. We performed a proteomic analysis of the hippocampus of STZ rats using two-dimensional gel electrophoresis followed by mass spectrometry. The distribution of 14–3-3 proteins identified by the proteomic analysis was then examined using immunohistochemistry. The results obtained revealed that 14–3-3 η immunoreactivity in the dorsal hippocampus was weaker in STZ rats than in age-matched control rats. Moreover, the density of glial fibrillary acidic protein-immunoreactive astrocytes in the dorsal hippocampus of STZ rats was increased, whereas 14–3-3 η immunoreactivity in astrocytes and neurons in the dentate gyrus was significantly decreased. These results suggest that changes in 14–3-3 η expression are involved in hippocampal astrogliosis or/and neurogenesis in STZ rats.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138027"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546567","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}
Pub Date : 2024-10-28DOI: 10.1016/j.neulet.2024.138030
Mark Baron , Marshall Devor
Neurosteroids are endogenous molecules with anxiolytic, anticonvulsant, sleep-promoting and sedative effects. They are biosynthesized de novo within the brain, among other tissues, and are thought to act primarily as positive allosteric modulators of high-affinity extrasynaptic GABAAδ-receptors. The location of action of neurosteroids in the brain, however, remains unknown. We have demonstrated that GABAergic anesthetics act within the brainstem mesopontine tegmental anesthesia area (MPTA) to induce and maintain anesthetic loss-of-consciousness. Here we asked whether endogenous and synthetic neurosteroids might also act in the MPTA to induce their suppressive effects. Direct exposure of the MPTA to the endogenous neurosteroids pregnenolone and progesterone, their metabolites testosterone, allopregnanolone and 3α5α-THDOC, and the synthetic neurosteroids ganaxolone and alphaxalone, was found to be pro-anesthetic. Although we cannot rule out additional sites of action, results of this study suggest that the suppressive effects of neurosteroids are due, at least in part, to actions within the MPTA, presumably by recruitment of dedicated neuronal circuitry. This undermines the usual presumption that neurosteroids, like other sedatives, endogenous somnogens and anesthetics, act by nonspecific global distribution.
{"title":"Neurosteroids foster sedation by engaging tonic GABAA-Rs within the mesopontine tegmental anesthesia area (MPTA)","authors":"Mark Baron , Marshall Devor","doi":"10.1016/j.neulet.2024.138030","DOIUrl":"10.1016/j.neulet.2024.138030","url":null,"abstract":"<div><div>Neurosteroids are endogenous molecules with anxiolytic, anticonvulsant, sleep-promoting and sedative effects. They are biosynthesized <em>de novo</em> within the brain, among other tissues, and are thought to act primarily as positive allosteric modulators of high-affinity extrasynaptic GABA<sub>A</sub>δ-receptors. The location of action of neurosteroids in the brain, however, remains unknown. We have demonstrated that GABAergic anesthetics act within the brainstem mesopontine tegmental anesthesia area (MPTA) to induce and maintain anesthetic loss-of-consciousness. Here we asked whether endogenous and synthetic neurosteroids might also act in the MPTA to induce their suppressive effects. Direct exposure of the MPTA to the endogenous neurosteroids pregnenolone and progesterone, their metabolites testosterone, allopregnanolone and 3α5α-THDOC, and the synthetic neurosteroids ganaxolone and alphaxalone, was found to be pro-anesthetic. Although we cannot rule out additional sites of action, results of this study suggest that the suppressive effects of neurosteroids are due, at least in part, to actions within the MPTA, presumably by recruitment of dedicated neuronal circuitry. This undermines the usual presumption that neurosteroids, like other sedatives, endogenous somnogens and anesthetics, act by nonspecific global distribution.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138030"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568820","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}
Neurometabolic homeostasis in the brain depends on the coordinated transport of glucose and other essential substrates across brain barriers, primarily the blood-brain barrier and the blood-cerebrospinal fluid barrier. In type 2 diabetes mellitus (T2DM), persistent hyperglycemia disrupts these processes, leading to neurovascular dysfunction and cognitive impairment. This review examines how T2DM alters glucose and neurometabolite transport, emphasizing the role of glucose transporters and the astrocyte-neuron lactate shuttle in maintaining cerebral energy balance. Reduced expression of glucose transporters and impaired neurovascular coupling are key contributors to cognitive decline in T2DM. Additionally, the review highlights insulin’s pivotal role in the hippocampus, where it enhances neuro-glial coupling and modulates astrocyte glucose uptake to support neuronal energy demands. Synthesizing current findings, we underscore the importance of therapeutic strategies aimed at correcting glucose transport dysregulation to alleviate diabetes-associated cognitive decline.
{"title":"Neurometabolic substrate transport across brain barriers in diabetes mellitus: Implications for cognitive function and neurovascular health","authors":"Ritwick Mondal , Shramana Deb , Dipanjan Chowdhury , Shramana Sarkar , Aakash Guha Roy , Gourav Shome , Vramanti Sarkar , Durjoy Lahiri , Julián Benito-León","doi":"10.1016/j.neulet.2024.138028","DOIUrl":"10.1016/j.neulet.2024.138028","url":null,"abstract":"<div><div>Neurometabolic homeostasis in the brain depends on the coordinated transport of glucose and other essential substrates across brain barriers, primarily the blood-brain barrier and the blood-cerebrospinal fluid barrier. In type 2 diabetes mellitus (T2DM), persistent hyperglycemia disrupts these processes, leading to neurovascular dysfunction and cognitive impairment. This review examines how T2DM alters glucose and neurometabolite transport, emphasizing the role of glucose transporters and the astrocyte-neuron lactate shuttle in maintaining cerebral energy balance. Reduced expression of glucose transporters and impaired neurovascular coupling are key contributors to cognitive decline in T2DM. Additionally, the review highlights insulin’s pivotal role in the hippocampus, where it enhances neuro-glial coupling and modulates astrocyte glucose uptake to support neuronal energy demands. Synthesizing current findings, we underscore the importance of therapeutic strategies aimed at correcting glucose transport dysregulation to alleviate diabetes-associated cognitive decline.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138028"},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504938","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}
Pub Date : 2024-10-24DOI: 10.1016/j.neulet.2024.138025
Joanne Jingwen Li , Ayoub Daliri , Kwang S. Kim , Ludo Max
Previous studies have revealed that auditory processing is modulated during the planning phase immediately prior to speech onset. To date, the functional relevance of this pre-speech auditory modulation (PSAM) remains unknown. Here, we investigated whether PSAM reflects neuronal processes that are associated with preparing auditory cortex for optimized feedback monitoring as reflected in online speech corrections. Combining electroencephalographic PSAM data from a previous data set with new acoustic measures of the same participants’ speech, we asked whether individual speakers’ extent of PSAM is correlated with the implementation of within-vowel articulatory adjustments during /b/-vowel-/d/ word productions. Online articulatory adjustments were quantified as the extent of change in inter-trial formant variability from vowel onset to vowel midpoint (a phenomenon known as centering). This approach allowed us to also consider inter-trial variability in formant production, and its possible relation to PSAM, at vowel onset and midpoint separately. Results showed that inter-trial formant variability was significantly smaller at vowel midpoint than at vowel onset. PSAM was not significantly correlated with this amount of change in variability as an index of within-vowel adjustments. Surprisingly, PSAM was negatively correlated with inter-trial formant variability not only in the middle but also at the very onset of the vowels. Thus, speakers with more PSAM produced formants that were already less variable at vowel onset. Findings suggest that PSAM may reflect processes that influence speech acoustics as early as vowel onset and, thus, that are directly involved in motor command preparation (feedforward control) rather than output monitoring (feedback control).
{"title":"Does pre-speech auditory modulation reflect processes related to feedback monitoring or speech movement planning?","authors":"Joanne Jingwen Li , Ayoub Daliri , Kwang S. Kim , Ludo Max","doi":"10.1016/j.neulet.2024.138025","DOIUrl":"10.1016/j.neulet.2024.138025","url":null,"abstract":"<div><div>Previous studies have revealed that auditory processing is modulated during the planning phase immediately prior to speech onset. To date, the functional relevance of this pre-speech auditory modulation (PSAM) remains unknown. Here, we investigated whether PSAM reflects neuronal processes that are associated with preparing auditory cortex for optimized feedback monitoring as reflected in online speech corrections. Combining electroencephalographic PSAM data from a previous data set with new acoustic measures of the same participants’ speech, we asked whether individual speakers’ extent of PSAM is correlated with the implementation of within-vowel articulatory adjustments during /b/-vowel-/d/ word productions. Online articulatory adjustments were quantified as the extent of change in inter-trial formant variability from vowel onset to vowel midpoint (a phenomenon known as <em>centering</em>). This approach allowed us to also consider inter-trial variability in formant production, and its possible relation to PSAM, at vowel onset and midpoint separately. Results showed that inter-trial formant variability was significantly smaller at vowel midpoint than at vowel onset. PSAM was not significantly correlated with this amount of change in variability as an index of within-vowel adjustments. Surprisingly, PSAM was negatively correlated with inter-trial formant variability not only in the middle but also at the very onset of the vowels. Thus, speakers with more PSAM produced formants that were already less variable at vowel onset. Findings suggest that PSAM may reflect processes that influence speech acoustics as early as vowel onset and, thus, that are directly involved in motor command preparation (feedforward control) rather than output monitoring (feedback control).</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138025"},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504936","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}
Pub Date : 2024-10-24DOI: 10.1016/j.neulet.2024.138026
Angeliki Metaxia Styla, Nikolaos Pitsikas
Alzheimer’s Disease (AD) is a serious progressive neurodegenerative illness conducting to the decay of cognitive functions. A few drugs have been approved for the therapy of AD, including the acetylcholinesterase inhibitors (AChEIs) like donepezil. Their efficiency, however, is modest and their application is associated with toxicity. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, a rapidly acting antidepressant, has been proposed as a potential agent for the treatment of AD. The present study was designed to investigate the effects exerted by the combination of sub-threshold doses of donepezil with those of ketamine on rats’ recognition memory abilities. For these experiments, the object recognition task (ORT) and the object location task (OLT), two procedures assessing non-spatial and spatial recognition memory respectively in rodents were used. Post-training acute administration of inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) counteracted non-spatial and spatial recognition memory impairments. The present findings, although preliminary, propose that the combined administration of ketamine and donepezil could represent a new strategy for the therapy of memory disorders, a common feature of AD patients.
{"title":"Joint administration of sub-threshold doses of the acetylcholinesterase inhibitor donepezil with those of the NMDA receptor antagonist ketamine improved rats’ recognition memory abilities","authors":"Angeliki Metaxia Styla, Nikolaos Pitsikas","doi":"10.1016/j.neulet.2024.138026","DOIUrl":"10.1016/j.neulet.2024.138026","url":null,"abstract":"<div><div>Alzheimer’s Disease (AD) is a serious progressive neurodegenerative illness conducting to the decay of cognitive functions. A few drugs have been approved for the therapy of AD, including the acetylcholinesterase inhibitors (AChEIs) like donepezil. Their efficiency, however, is modest and their application is associated with toxicity. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, a rapidly acting antidepressant, has been proposed as a potential agent for the treatment of AD. The present study was designed to investigate the effects exerted by the combination of sub-threshold doses of donepezil with those of ketamine on rats’ recognition memory abilities. For these experiments, the object recognition task (ORT) and the object location task (OLT), two procedures assessing non-spatial and spatial recognition memory respectively in rodents were used. Post-training acute administration of inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) counteracted non-spatial and spatial recognition memory impairments. The present findings, although preliminary, propose that the combined administration of ketamine and donepezil could represent a new strategy for the therapy of memory disorders, a common feature of AD patients.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138026"},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504937","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}
Pub Date : 2024-10-22DOI: 10.1016/j.neulet.2024.138029
Bernard A.J. Jap , Yu-Yin Hsu , Stephen Politzer-Ahles
This study compares the processing of cleft structures against that of monoclausal sentences using event-related potential (ERP). We aim to understand how syntactic complexity is processed by comparing the neural response to cleft and single-clause sentences with identical verb phrases, controlling for verb bias frequency effects. Sixty participants were tested, and we presented 100 cleft and 100 monoclausal sentences, balanced for active and passive verb usage. We examined the P600 component, an ERP associated with syntactic complexity, to assess the processing of cleft structures. Results showed that cleft structures incur a greater processing load, as indicated by a larger P600, compared to monoclausal sentences. The P600 response indicates that processing cleft sentences requires additional syntactic operations, consistent with behavioral studies showing that clinical populations have difficulty comprehending complex sentences.
{"title":"Are cleft sentence structures more difficult to process?","authors":"Bernard A.J. Jap , Yu-Yin Hsu , Stephen Politzer-Ahles","doi":"10.1016/j.neulet.2024.138029","DOIUrl":"10.1016/j.neulet.2024.138029","url":null,"abstract":"<div><div>This study compares the processing of cleft structures against that of monoclausal sentences using event-related potential (ERP). We aim to understand how syntactic complexity is processed by comparing the neural response to cleft and single-clause sentences with identical verb phrases, controlling for verb bias frequency effects. Sixty participants were tested, and we presented 100 cleft and 100 monoclausal sentences, balanced for active and passive verb usage. We examined the P600 component, an ERP associated with syntactic complexity, to assess the processing of cleft structures. Results showed that cleft structures incur a greater processing load, as indicated by a larger P600, compared to monoclausal sentences. The P600 response indicates that processing cleft sentences requires additional syntactic operations, consistent with behavioral studies showing that clinical populations have difficulty comprehending complex sentences.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138029"},"PeriodicalIF":2.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504935","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}
The distribution of Fos expression in catecholaminergic neurons with immunoreactivity for dopamine β-hydroxylase (DBH) of the ventrolateral medulla was compared between rats exposed to hypoxia (10 % O2), hypercapnia (8 % CO2), and hypercapnic hypoxia (8 % CO2 and 10 % O2) for 2 h. Among the experimental groups, hypoxia-exposed rats had more Fos/DBH double-immunoreactive neurons than the control group (20 % O2) in the rostral area of the ventrolateral medulla, specifically in the range of + 150 μm to + 2,400 μm from the caudal end of the facial nerve nucleus. On the other hand, Fos/DBH double-immunoreactive neurons were scarcely observed in the ventrolateral medullary region of hypercapnia-exposed rats. The number of double-immunoreactive neurons in hypercapnic hypoxia-exposed rats was comparable to that in the control group. The present results suggest that adrenergic C1 neurons are specifically activated by hypoxia and are involved in the regulation of respiratory and circulatory functions.
{"title":"Fos expression in A1/C1 neurons of rats exposed to hypoxia, hypercapnia, or hypercapnic hypoxia","authors":"Kouki Kato , Risa Serizawa , Takuya Yokoyama , Nobuaki Nakamuta , Yoshio Yamamoto","doi":"10.1016/j.neulet.2024.138024","DOIUrl":"10.1016/j.neulet.2024.138024","url":null,"abstract":"<div><div>The distribution of Fos expression in catecholaminergic neurons with immunoreactivity for dopamine β-hydroxylase (DBH) of the ventrolateral medulla was compared between rats exposed to hypoxia (10 % O<sub>2</sub>), hypercapnia (8 % CO<sub>2</sub>), and hypercapnic hypoxia (8 % CO<sub>2</sub> and 10 % O<sub>2</sub>) for 2 h. Among the experimental groups, hypoxia-exposed rats had more Fos/DBH double-immunoreactive neurons than the control group (20 % O<sub>2</sub>) in the rostral area of the ventrolateral medulla, specifically in the range of + 150 μm to + 2,400 μm from the caudal end of the facial nerve nucleus. On the other hand, Fos/DBH double-immunoreactive neurons were scarcely observed in the ventrolateral medullary region of hypercapnia-exposed rats. The number of double-immunoreactive neurons in hypercapnic hypoxia-exposed rats was comparable to that in the control group. The present results suggest that adrenergic C1 neurons are specifically activated by hypoxia and are involved in the regulation of respiratory and circulatory functions.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138024"},"PeriodicalIF":2.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504939","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}
Pub Date : 2024-10-22DOI: 10.1016/j.neulet.2024.138014
Yihao Sun , Bin Tian , Jiali Liang , Meiru Bu , Xi Deng , Kemei Deng , Muliang Jiang , Bihong T. Chen
Background
Brain iron overload may induce neuronal death and lead to cognitive impairment. The hippocampus is a critical limbic structure involved in memory. This study aimed to investigate iron overload and its role in hippocampal damage and memory impairment using a rat model.
Methods
Young rats (2 weeks old) received intraperitoneal injections of high-dose iron solution (Group H, n = 10), low-dose iron solution (Group L, n = 10) and normal saline as control (Group D, n = 5). The Morris water maze (MWM) test was performed on all rats to evaluate their spatial reference memory by assessing their escape latency time and number of platform crossing. The iron content and neuronal damage in hippocampal tissue sections of the rats were assessed semi-quantitatively using diaminobenzidine (DAB)-enhanced Perl’s Prussian blue (PPB) staining, and their correlation with spatial reference memory performance was evaluated.
Results
The escape latency in Group H was significantly longer compared to Groups L and D (P < 0.05). The number of platform crossings was significantly lower in Group H than in Group L or D (P < 0.001). The neuronal cells in Group H had more brown iron deposits than those of Groups L and D. There were significant correlations between the severity of structural damage in the hippocampal tissue and the number of platform crossings (P1 = 0.001 for Group H; P2 = 0.043 for Group L).
Conclusion
This study showed an association between hippocampal iron-induced structural damage and spatial reference memory impairment in a rat model. This work should advance our understanding of hippocampal iron overload on cognitive functioning.
{"title":"Hippocampal iron overload and spatial reference memory impairment: Insights from a rat model","authors":"Yihao Sun , Bin Tian , Jiali Liang , Meiru Bu , Xi Deng , Kemei Deng , Muliang Jiang , Bihong T. Chen","doi":"10.1016/j.neulet.2024.138014","DOIUrl":"10.1016/j.neulet.2024.138014","url":null,"abstract":"<div><h3>Background</h3><div>Brain iron overload may induce neuronal death and lead to cognitive impairment. The hippocampus is a critical limbic structure involved in memory. This study aimed to investigate iron overload and its role in hippocampal damage and memory impairment using a rat model.</div></div><div><h3>Methods</h3><div>Young rats (2 weeks old) received intraperitoneal injections of high-dose iron solution (Group H, n = 10), low-dose iron solution (Group L, n = 10) and normal saline as control (Group D, n = 5). The Morris water maze (MWM) test was performed on all rats to evaluate their spatial reference memory by assessing their escape latency time and number of platform crossing. The iron content and neuronal damage in hippocampal tissue sections of the rats were assessed semi-quantitatively using diaminobenzidine (DAB)-enhanced Perl’s Prussian blue (PPB) staining, and their correlation with spatial reference memory performance was evaluated.</div></div><div><h3>Results</h3><div>The escape latency in Group H was significantly longer compared to Groups L and D (<em>P</em> < 0.05). The number of platform crossings was significantly lower in Group H than in Group L or D (<em>P</em> < 0.001). The neuronal cells in Group H had more brown iron deposits than those of Groups L and D. There were significant correlations between the severity of structural damage in the hippocampal tissue and the number of platform crossings (<em>P<sub>1</sub></em> = 0.001 for Group H; <em>P<sub>2</sub></em> = 0.043 for Group L).</div></div><div><h3>Conclusion</h3><div>This study showed an association between hippocampal iron-induced structural damage and spatial reference memory impairment in a rat model. This work should advance our understanding of hippocampal iron overload on cognitive functioning.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138014"},"PeriodicalIF":2.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504940","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}
Pub Date : 2024-10-18DOI: 10.1016/j.neulet.2024.138013
Marco Anzalone , Sarmad A. Karam , Sanne R.R. Briting , Sussanne Petersen , Majken B. Thomsen , Alicia A. Babcock , Anne M. Landau , Bente Finsen , Athanasios Metaxas
Despite well-documented dysregulation in central serotonergic signaling in Alzheimer’s disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HT2BR) subtype remains sparse. Here, we assessed the levels of 5-HT2BRs in brain tissue from APPswe/PS1dE9 transgenic (TG) mice, AD patients, and adult microglial cells. 5-HT2BR mRNA was measured by RT-qPCR in ageing TG and wild-type (WT) mice, in samples from the middle frontal gyrus of female, AD and control subjects, and in microglia from the cerebral cortex of WT mice. The density of 5-HT2BRs was measured by autoradiography using [3H]RS 127445. Both mouse and human brains had low levels of 5-HT2BR mRNA. In whole-brain mouse samples, mRNA expression was significantly lower in TG mice compared to WT at > 18 months of age. In the Aβ-plaque-burdened neocortex and hippocampus of old TG mice, however, levels of 5-HT2BR mRNA were two-fold higher over control, with similar elevations observed in the Aβ-plaque-burdened frontal cortex of human AD patients. 5-HT2BR mRNA expression varied widely in adult microglia and was higher compared to other cortical cell subtypes. In mice, specific [3H]RS-127445 binding in the cortex was first detected after 3 months of age. The density of 5-HT2BRs was low and overall reduced in TG, compared to WT mice. Binding was detectable but too low to be reliably quantified in the human cortex. Our results document Aβ-associated increases in 5-HT2BR mRNA expression and suggest reduced receptor binding in the context of AD. Studies investigating the functional involvement of microglial 5-HT2BRs in AD are considered relevant.
{"title":"Serotonin-2B receptor (5-HT2BR) expression and binding in the brain of APPswe/PS1dE9 transgenic mice and in Alzheimer’s disease brain tissue","authors":"Marco Anzalone , Sarmad A. Karam , Sanne R.R. Briting , Sussanne Petersen , Majken B. Thomsen , Alicia A. Babcock , Anne M. Landau , Bente Finsen , Athanasios Metaxas","doi":"10.1016/j.neulet.2024.138013","DOIUrl":"10.1016/j.neulet.2024.138013","url":null,"abstract":"<div><div>Despite well-documented dysregulation in central serotonergic signaling in Alzheimer’s disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HT<sub>2B</sub>R) subtype remains sparse. Here, we assessed the levels of 5-HT<sub>2B</sub>Rs in brain tissue from <em>APP<sub>swe</sub>/PS1<sub>dE9</sub></em> transgenic (TG) mice, AD patients, and adult microglial cells. 5-HT<sub>2B</sub>R mRNA was measured by RT-qPCR in ageing TG and wild-type (WT) mice, in samples from the middle frontal gyrus of female, AD and control subjects, and in microglia from the cerebral cortex of WT mice. The density of 5-HT<sub>2B</sub>Rs was measured by autoradiography using [<sup>3</sup>H]RS 127445. Both mouse and human brains had low levels of 5-HT<sub>2B</sub>R mRNA. In whole-brain mouse samples, mRNA expression was significantly lower in TG mice compared to WT at > 18 months of age. In the Aβ-plaque-burdened neocortex and hippocampus of old TG mice, however, levels of 5-HT<sub>2B</sub>R mRNA were two-fold higher over control, with similar elevations observed in the Aβ-plaque-burdened frontal cortex of human AD patients. 5-HT<sub>2B</sub>R mRNA expression varied widely in adult microglia and was higher compared to other cortical cell subtypes. In mice, specific [<sup>3</sup>H]RS-127445 binding in the cortex was first detected after 3 months of age. The density of 5-HT<sub>2B</sub>Rs was low and overall reduced in TG, compared to WT mice. Binding was detectable but too low to be reliably quantified in the human cortex. Our results document Aβ-associated increases in 5-HT<sub>2B</sub>R mRNA expression and suggest reduced receptor binding in the context of AD. Studies investigating the functional involvement of microglial 5-HT<sub>2B</sub>Rs in AD are considered relevant.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138013"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471065","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}
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