Progress in Neurobiology最新文献_第6页

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-06-13 DOI: 10.1016/j.pneurobio.2024.102637

Ying Huang , Michael Brosch

引用次数: 0

TRPV1 channel in the pathophysiology of epilepsy and its potential as a molecular target for the development of new antiseizure drug candidates 癫痫病理生理学中的 TRPV1 通道及其作为候选抗癫痫新药开发分子靶点的潜力

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-06-02 DOI: 10.1016/j.pneurobio.2024.102634

Katarzyna Socała , Marcin Jakubiec , Michał Abram , Jakub Mlost , Katarzyna Starowicz , Rafał M. Kamiński , Katarzyna Ciepiela , Marta Andres-Mach , Mirosław Zagaja , Cameron S. Metcalf , Przemysław Zawadzki , Piotr Wlaź , Krzysztof Kamiński

{"title":"TRPV1 channel in the pathophysiology of epilepsy and its potential as a molecular target for the development of new antiseizure drug candidates","authors":"Katarzyna Socała , Marcin Jakubiec , Michał Abram , Jakub Mlost , Katarzyna Starowicz , Rafał M. Kamiński , Katarzyna Ciepiela , Marta Andres-Mach , Mirosław Zagaja , Cameron S. Metcalf , Przemysław Zawadzki , Piotr Wlaź , Krzysztof Kamiński","doi":"10.1016/j.pneurobio.2024.102634","DOIUrl":"10.1016/j.pneurobio.2024.102634","url":null,"abstract":"<div><p>Identification of transient receptor potential cation channel, subfamily V member 1 (TRPV1), also known as capsaicin receptor, in 1997 was a milestone achievement in the research on temperature sensation and pain signalling. Very soon after it became evident that TRPV1 is implicated in a wide array of physiological processes in different peripheral tissues, as well as in the central nervous system, and thereby could be involved in the pathophysiology of numerous diseases. Increasing evidence suggests that modulation of TRPV1 may also affect seizure susceptibility and epilepsy. This channel is localized in brain regions associated with seizures and epilepsy, and its overexpression was found both in animal models of seizures and in brain samples from epileptic patients. Moreover, modulation of TRPV1 on non-neuronal cells (microglia, astrocytes, and/or peripheral immune cells) may have an impact on the neuroinflammatory processes that play a role in epilepsy and epileptogenesis. In this paper, we provide a comprehensive and critical overview of currently available data on TRPV1 as a possible molecular target for epilepsy management, trying to identify research gaps and future directions. Overall, several converging lines of evidence implicate TRPV1 channel as a potentially attractive target in epilepsy research but more studies are needed to exploit the possible role of TRPV1 in seizures/epilepsy and to evaluate the value of TRPV1 ligands as candidates for new antiseizure drugs.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102634"},"PeriodicalIF":6.7,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141228952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Experience-dependent regulation of dopaminergic signaling in the somatosensory cortex 体感皮层多巴胺能信号传导的经验依赖性调节

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-06-02 DOI: 10.1016/j.pneurobio.2024.102630

Tousif Jamal , Xuan Yan , Angelica da Silva Lantyer , Judith G. ter Horst , Tansu Celikel

{"title":"Experience-dependent regulation of dopaminergic signaling in the somatosensory cortex","authors":"Tousif Jamal , Xuan Yan , Angelica da Silva Lantyer , Judith G. ter Horst , Tansu Celikel","doi":"10.1016/j.pneurobio.2024.102630","DOIUrl":"10.1016/j.pneurobio.2024.102630","url":null,"abstract":"<div><p>Dopamine critically influences reward processing, sensory perception, and motor control. Yet, the modulation of dopaminergic signaling by sensory experiences is not fully delineated. Here, by manipulating sensory experience using bilateral single-row whisker deprivation, we demonstrated that gene transcription in the dopaminergic signaling pathway (<em>DSP</em>) undergoes experience-dependent plasticity in both granular and supragranular layers of the primary somatosensory (barrel) cortex (<em>S</em>1). Sensory experience and deprivation compete for the regulation of <em>DSP</em> transcription across neighboring cortical columns, and sensory deprivation-induced changes in <em>DSP</em> are topographically constrained. These changes in <em>DSP</em> extend beyond cortical map plasticity and influence neuronal information processing. Pharmacological regulation of D2 receptors, a key component of <em>DSP</em>, revealed that D2 receptor activation suppresses excitatory neuronal excitability, hyperpolarizes the action potential threshold, and reduces the instantaneous firing rate. These findings suggest that the dopaminergic drive originating from midbrain dopaminergic neurons, targeting the sensory cortex, is subject to experience-dependent regulation and might create a regulatory feedback loop for modulating sensory processing. Finally, using topological gene network analysis and mutual information, we identify the molecular hubs of experience-dependent plasticity of <em>DSP</em>. These findings provide new insights into the mechanisms by which sensory experience shapes dopaminergic signaling in the brain and might help unravel the sensory deficits observed after dopamine depletion.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"239 ","pages":"Article 102630"},"PeriodicalIF":6.7,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141228839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A theory of hippocampal function: New developments 海马功能理论：新进展

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-06-02 DOI: 10.1016/j.pneurobio.2024.102636

Edmund T. Rolls , Alessandro Treves

{"title":"A theory of hippocampal function: New developments","authors":"Edmund T. Rolls , Alessandro Treves","doi":"10.1016/j.pneurobio.2024.102636","DOIUrl":"10.1016/j.pneurobio.2024.102636","url":null,"abstract":"<div><p>We develop further here the only quantitative theory of the storage of information in the hippocampal episodic memory system and its recall back to the neocortex. The theory is upgraded to account for a revolution in understanding of spatial representations in the primate, including human, hippocampus, that go beyond the place where the individual is located, to the location being viewed in a scene. This is fundamental to much primate episodic memory and navigation: functions supported in humans by pathways that build ‘where’ spatial view representations by feature combinations in a ventromedial visual cortical stream, separate from those for ‘what’ object and face information to the inferior temporal visual cortex, and for reward information from the orbitofrontal cortex. Key new computational developments include the capacity of the CA3 attractor network for storing whole charts of space; how the correlations inherent in self-organizing continuous spatial representations impact the storage capacity; how the CA3 network can combine continuous spatial and discrete object and reward representations; the roles of the rewards that reach the hippocampus in the later consolidation into long-term memory in part via cholinergic pathways from the orbitofrontal cortex; and new ways of analysing neocortical information storage using Potts networks.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"238 ","pages":"Article 102636"},"PeriodicalIF":6.7,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000728/pdfft?md5=e792602997e8ebff53c4e95af5dbc3e9&pid=1-s2.0-S0301008224000728-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141228908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multimodal mapping of macaque monkey somatosensory cortex 猕猴躯体感觉皮层的多模式绘图

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-06-01 DOI: 10.1016/j.pneurobio.2024.102633

Meiqi Niu , Lucija Rapan , Seán Froudist-Walsh , Ling Zhao , Thomas Funck , Katrin Amunts , Nicola Palomero-Gallagher

{"title":"Multimodal mapping of macaque monkey somatosensory cortex","authors":"Meiqi Niu , Lucija Rapan , Seán Froudist-Walsh , Ling Zhao , Thomas Funck , Katrin Amunts , Nicola Palomero-Gallagher","doi":"10.1016/j.pneurobio.2024.102633","DOIUrl":"10.1016/j.pneurobio.2024.102633","url":null,"abstract":"<div><p>The somatosensory cortex is a brain region responsible for receiving and processing sensory information from across the body and is structurally and functionally heterogeneous. Since the chemoarchitectonic segregation of the cerebral cortex can be revealed by transmitter receptor distribution patterns, by using a quantitative multireceptor architectonical analysis, we determined the number and extent of distinct areas of the macaque somatosensory cortex. We identified three architectonically distinct cortical entities within the primary somatosensory cortex (i.e., 3bm, 3bli, 3ble), four within the anterior parietal cortex (i.e., 3am, 3al, 1 and 2) and six subdivisions (i.e., S2l, S2m, PVl, PVm, PRl and PRm) within the lateral fissure. We provide an ultra-high resolution 3D atlas of macaque somatosensory areas in stereotaxic space, which integrates cyto- and receptor architectonic features of identified areas. Multivariate analyses of the receptor fingerprints revealed four clusters of identified areas based on the degree of (dis)similarity of their receptor architecture. Each of these clusters can be associated with distinct levels of somatosensory processing, further demonstrating that the functional segregation of cortical areas is underpinned by differences in their molecular organization.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"239 ","pages":"Article 102633"},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000698/pdfft?md5=520ea428ca44bd90fb9aa8023a2674e4&pid=1-s2.0-S0301008224000698-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141233268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calcium plays an essential role in early-stage dendrite injury detection and regeneration 钙在早期树突损伤检测和再生中发挥着至关重要的作用。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-05-31 DOI: 10.1016/j.pneurobio.2024.102635

Vinicius N. Duarte , Vicky T. Lam , Dario S. Rimicci , Katherine L. Thompson-Peer

{"title":"Calcium plays an essential role in early-stage dendrite injury detection and regeneration","authors":"Vinicius N. Duarte , Vicky T. Lam , Dario S. Rimicci , Katherine L. Thompson-Peer","doi":"10.1016/j.pneurobio.2024.102635","DOIUrl":"10.1016/j.pneurobio.2024.102635","url":null,"abstract":"<div><p>Dendrites are injured in a variety of clinical conditions such as traumatic brain and spinal cord injuries and stroke. How neurons detect injury directly to their dendrites to initiate a pro-regenerative response has not yet been thoroughly investigated. Calcium plays a critical role in the early stages of axonal injury detection and is also indispensable for regeneration of the severed axon. Here, we report cell and neurite type-specific differences in laser injury-induced elevations of intracellular calcium levels. Using a human KCNJ2 transgene, we demonstrate that hyperpolarizing neurons only at the time of injury dampens dendrite regeneration, suggesting that inhibition of injury-induced membrane depolarization (and thus early calcium influx) plays a role in detecting and responding to dendrite injury. In exploring potential downstream calcium-regulated effectors, we identify L-type voltage-gated calcium channels, inositol triphosphate signaling, and protein kinase D activity as drivers of dendrite regeneration. In conclusion, we demonstrate that dendrite injury-induced calcium elevations play a key role in the regenerative response of dendrites and begin to delineate the molecular mechanisms governing dendrite repair.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"239 ","pages":"Article 102635"},"PeriodicalIF":6.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000716/pdfft?md5=a0adc6d1c7949f6dab645403af92ebc7&pid=1-s2.0-S0301008224000716-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A molecularly defined orbitofrontal cortical neuron population controls compulsive-like behavior, but not inflexible choice or habit 一个分子定义的眶额叶皮层神经元群控制着类似强迫症的行为，但不控制不灵活的选择或习惯。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-05-29 DOI: 10.1016/j.pneurobio.2024.102632

Sophie T. Yount , Silu Wang , Aylet T. Allen , Lauren P. Shapiro , Laura M. Butkovich , Shannon L. Gourley

{"title":"A molecularly defined orbitofrontal cortical neuron population controls compulsive-like behavior, but not inflexible choice or habit","authors":"Sophie T. Yount , Silu Wang , Aylet T. Allen , Lauren P. Shapiro , Laura M. Butkovich , Shannon L. Gourley","doi":"10.1016/j.pneurobio.2024.102632","DOIUrl":"10.1016/j.pneurobio.2024.102632","url":null,"abstract":"<div><p>Habits are familiar behaviors triggered by cues, not outcome predictability, and are insensitive to changes in the environment. They are adaptive under many circumstances but can be considered antecedent to compulsions and intrusive thoughts that drive persistent, potentially maladaptive behavior. Whether compulsive-like and habit-like behaviors share neural substrates is still being determined. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences. We found that these mice demonstrate habitual response biases and compulsive-like grooming behavior that was reversible by fluoxetine and ketamine. They also suffer dendritic spine attrition on excitatory neurons in the orbitofrontal cortex (OFC). Nevertheless, synaptic melanocortin 4 receptor (MC4R), a factor implicated in compulsive behavior, is preserved, leading to the hypothesis that <em>Mc4r</em>+ OFC neurons may drive aberrant behaviors. Repeated chemogenetic stimulation of <em>Mc4r+</em> OFC neurons triggered compulsive and not inflexible or habitual response biases in otherwise typical mice. Thus, <em>Mc4r</em>+ neurons within the OFC appear to drive compulsive-like behavior that is dissociable from habitual behavior. Understanding which neuron populations trigger distinct behaviors may advance efforts to mitigate harmful compulsions.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"238 ","pages":"Article 102632"},"PeriodicalIF":6.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Control of goal-directed and inflexible actions by dorsal striatal melanocortin systems, in coordination with the central nucleus of the amygdala 背侧纹状体黑皮质素系统与杏仁核中枢核协调控制目标定向和不灵活的行动

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-05-17 DOI: 10.1016/j.pneurobio.2024.102629

Elizabeth C. Heaton , Esther H. Seo , Laura M. Butkovich , Sophie T. Yount , Shannon L. Gourley

{"title":"Control of goal-directed and inflexible actions by dorsal striatal melanocortin systems, in coordination with the central nucleus of the amygdala","authors":"Elizabeth C. Heaton , Esther H. Seo , Laura M. Butkovich , Sophie T. Yount , Shannon L. Gourley","doi":"10.1016/j.pneurobio.2024.102629","DOIUrl":"10.1016/j.pneurobio.2024.102629","url":null,"abstract":"<div><p>The dorsomedial striatum (DMS) is associated with flexible goal seeking, as opposed to routinized habits. Whether local mechanisms brake this function, for instance when habits may be adaptive, is incompletely understood. We find that a sub-population of dopamine D1 receptor-containing striatal neurons express the melanocortin-4 receptor (MC4R) for α-melanocyte stimulating hormone. These neurons within the DMS are necessary and sufficient for controlling the capacity of mice to flexibly adjust actions based on the likelihood that they will be rewarded. In investigating MC4R function, we found that it suppresses immediate-early gene levels in the DMS and concurrently, flexible goal seeking. MC4R+ neurons receive input from the central nucleus of the amygdala, and behavioral experiments indicate that they are functionally integrated into an amygdalo-striatal circuit that suppresses action flexibility in favor of routine. Publicly available spatial transcriptomics datasets were analyzed for gene transcript correlates of <em>Mc4r</em> expression across the striatal subregions, revealing considerable co-variation in dorsal structures. This insight led to the discovery that the function of MC4R in the dorsolateral striatum complements that in the DMS, in this case suppressing habit-like behavior. Altogether, our findings suggest that striatal MC4R controls the capacity for goal-directed and inflexible actions alike.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"238 ","pages":"Article 102629"},"PeriodicalIF":6.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141028527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model 阿尔茨海默氏症小鼠模型中凹凸核甘氨酸受体的缺失与乙醇奖赏

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-05-07 DOI: 10.1016/j.pneurobio.2024.102616

Lorena Armijo-Weingart , Loreto San Martin , Scarlet Gallegos , Anibal Araya , Macarena Konar-Nie , Eduardo Fernandez-Pérez , Luis G. Aguayo

{"title":"Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model","authors":"Lorena Armijo-Weingart , Loreto San Martin , Scarlet Gallegos , Anibal Araya , Macarena Konar-Nie , Eduardo Fernandez-Pérez , Luis G. Aguayo","doi":"10.1016/j.pneurobio.2024.102616","DOIUrl":"10.1016/j.pneurobio.2024.102616","url":null,"abstract":"<div><p>Alterations in cognitive and non-cognitive cerebral functions characterize Alzheimer's disease (AD). Cortical and hippocampal impairments related to extracellular accumulation of Aβ in AD animal models have been extensively investigated. However, recent reports have also implicated intracellular Aβ in limbic regions, such as the nucleus accumbens (nAc). Accumbal neurons express high levels of inhibitory glycine receptors (GlyRs) that are allosterically modulated by ethanol and have a role in controlling its intake. In the present study, we investigated how GlyRs in the 2xTg mice (AD model) affect nAc functions and ethanol intake behavior. Using transgenic and control aged-matched litter mates, we found that the GlyRα2 subunit was significantly decreased in AD mice (6-month-old). We also examined intracellular calcium dynamics using the fluorescent calcium protein reporter GCaMP in slice photometry. We also found that the calcium signal mediated by GlyRs, but not GABA<sub>A</sub>R, was also reduced in AD neurons. Additionally, ethanol potentiation was significantly decreased in accumbal neurons in the AD mice. Finally, we performed drinking in the dark (DID) experiments and found that 2xTg mice consumed less ethanol on the last day of DID, in agreement with a lower blood ethanol concentration. 2xTg mice also showed lower sucrose consumption, indicating that overall food reward was altered. In conclusion, the data support the role of GlyRs in nAc neuron excitability and a decreased glycinergic activity in the 2xTg mice that might lead to impairment in reward processing at an early stage of the disease.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"237 ","pages":"Article 102616"},"PeriodicalIF":6.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice 持续的 ∆FosB 表达限制了 APP 小鼠齿状回的复发性癫痫发作活动并提供神经保护

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-04-19 DOI: 10.1016/j.pneurobio.2024.102612

Gabriel S. Stephens , Jin Park , Andrew Eagle , Jason You , Manuel Silva-Pérez , Chia-Hsuan Fu , Sumin Choi , Corey P. St. Romain , Chiho Sugimoto , Shelly A. Buffington , Yi Zheng , Mauro Costa-Mattioli , Yin Liu , A.J. Robison , Jeannie Chin

{"title":"Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice","authors":"Gabriel S. Stephens , Jin Park , Andrew Eagle , Jason You , Manuel Silva-Pérez , Chia-Hsuan Fu , Sumin Choi , Corey P. St. Romain , Chiho Sugimoto , Shelly A. Buffington , Yi Zheng , Mauro Costa-Mattioli , Yin Liu , A.J. Robison , Jeannie Chin","doi":"10.1016/j.pneurobio.2024.102612","DOIUrl":"10.1016/j.pneurobio.2024.102612","url":null,"abstract":"<div><p>Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer’s disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"237 ","pages":"Article 102612"},"PeriodicalIF":6.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140794335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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