Progress in Neurobiology最新文献

{"title":"Current amyloid inhibitors: Therapeutic applications and nanomaterial-based innovations","authors":"Paula López-García ,&nbsp;María M. Tejero-Ojeda ,&nbsp;María Eugenia Vaquero,&nbsp;Mariano Carrión-Vázquez","doi":"10.1016/j.pneurobio.2025.102734","DOIUrl":"10.1016/j.pneurobio.2025.102734","url":null,"abstract":"<div><div>Amyloid proteins have long been in the spotlight for being involved in many degenerative diseases including Alzheimer´s, Parkinson´s or type 2 diabetes, which currently cannot be prevented and for which there is no effective treatment or cure. Here we provide a comprehensive review of inhibitors that act directly on the amyloidogenic pathway (at the monomer, oligomer or fibril level) of key pathological amyloids, focusing on the most representative amyloid-related diseases. We discuss the latest advances in preclinical and clinical trials, focusing on cutting-edge developments, particularly on nanomaterials-based inhibitors, which offer unprecedented opportunities to address the complexity of protein misfolding disorders and are revolutionizing the landscape of anti-amyloid therapeutics. Notably, nanomaterials are impacting critical areas such as bioavailability, penetrability and functionality of compounds currently used in biomedicine, paving the way for more specific therapeutic solutions tailored to various amyloid-related diseases. Finally, we highlight the window of opportunity opened by comparative analysis with so-called functional amyloids for the development of innovative therapeutic approaches for these devastating diseases.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102734"},"PeriodicalIF":6.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537670","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}

{"title":"Dynamics of hippocampal reactivation for temporal association memory in mice","authors":"Hui Chen ,&nbsp;Bin Wang ,&nbsp;Yue Zhan ,&nbsp;Junqi Liu ,&nbsp;Sicheng Yang ,&nbsp;Xuan Tan ,&nbsp;Weiwei Zhang ,&nbsp;Jie Zhang ,&nbsp;Ye Yang ,&nbsp;Yanji Liu ,&nbsp;Meilin Wang ,&nbsp;Haibo Zhang ,&nbsp;Xuan Li ,&nbsp;Zhongxiang Yao ,&nbsp;Drolma Pema ,&nbsp;Hongli Li ,&nbsp;Hao Chen ,&nbsp;Bo Hu","doi":"10.1016/j.pneurobio.2025.102729","DOIUrl":"10.1016/j.pneurobio.2025.102729","url":null,"abstract":"<div><div>Reactivation refers to the re-emergence of activity in neuronal ensembles that were active during information encoding. Hippocampal CA1 neuronal ensembles generate firing activities that encode the temporal association among time-separated events. However, whether and how temporal association memory-related CA1 neuronal ensembles reactivate during sleep and their role in temporal association memory consolidation remain unclear. We utilized multiple unit recordings to monitor CA1 neuronal activity in mice learning a trace eyeblink conditioning (tEBC) task, in which presentation of the conditioned stimulus (CS, a light flash) was paired with presentation of the unconditioned stimulus (US, corneal puff) by a time-separated interval. We found that the CS-US paired training mice exhibited few conditioned eyeblink responses (CRs) at the initial-learning stage (ILS) and an asymptotic level of CRs at the well-learning stage (WLS). More than one third of CA1 pyramidal cells (PYR) in the CS-US paired training mice manifested a CS-evoked firing activity that was sustained from the CS to time-separated interval. The CS-evoked PYR firing activity was required for the tEBC acquisition and was greater when the CRs occurred. Intriguingly, the CS-evoked firing PYR ensembles reactivated, which coincided with increased hippocampal ripples during post-training sleep. The reactivation of CS-evoked firing PYR ensembles diminished across learning stages, with greater strength in the ILS. Disrupting the ripple-associated PYR activity impaired both the reactivation of CS-evoked firing PYR ensembles and tEBC consolidation. Our findings highlight the features of hippocampal CA1 neuronal ensemble reactivation during sleep, which support the consolidation of temporal association memory.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102729"},"PeriodicalIF":6.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537673","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}

{"title":"The role of TREM2 in myelin sheath dynamics: A comprehensive perspective from physiology to pathology","authors":"Xinwei Que ,&nbsp;Tongtong Zhang ,&nbsp;Xueyu Liu ,&nbsp;Yunsi Yin ,&nbsp;Xinyi Xia ,&nbsp;Ping Gong ,&nbsp;Weiyi Song ,&nbsp;Qi Qin ,&nbsp;Zhi-Qing David Xu ,&nbsp;Yi Tang","doi":"10.1016/j.pneurobio.2025.102732","DOIUrl":"10.1016/j.pneurobio.2025.102732","url":null,"abstract":"<div><div>Demyelinating disorders, characterizing by the loss of myelin integrity, present significant challenges due to their impact on neurological function and lack of effective treatments. Understanding the mechanisms underlying myelin damage is crucial for developing therapeutic strategies. Triggering receptor expressed on myeloid cells 2 (TREM2), a pivotal immune receptor predominantly found on microglial cells, plays essential roles in phagocytosis and lipid metabolism, vital processes in neuroinflammation and immune regulation. Emerging evidence indicates a close relationship between TREM2 and various aspects of myelin sheath dynamics, including maintenance, response to damage, and regeneration. This review provides a comprehensive discussion of TREM2's influence on myelin physiology and pathology, highlighting its therapeutic potential and putative mechanisms in the progression of demyelinating disorders.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102732"},"PeriodicalIF":6.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531862","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}

{"title":"Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease","authors":"Alejandro Antón-Fernández ,&nbsp;Álvaro Ruiz de Alegría ,&nbsp;Ana Mariscal-Casero ,&nbsp;Marta Roldán-Lázaro ,&nbsp;Rocío Peinado-Cauchola ,&nbsp;Jesús Ávila ,&nbsp;Félix Hernández","doi":"10.1016/j.pneurobio.2025.102743","DOIUrl":"10.1016/j.pneurobio.2025.102743","url":null,"abstract":"<div><div>Partial reprogramming induced by the controlled and cyclical overexpression of Yamanaka factors in the nervous system has so far succeeded in reversing some aging-associated phenotypes, such as improving memory function. These promising results suggest that partial reprogramming could be a potential strategy to prevent or mitigate aging-related pathologies like tauopathies, including Alzheimer’s disease. Here, we explore the potential of this strategy in addressing tauopathy development in the P301S mouse model. To achieve this, a new transgenic animal was created that can inducibly overexpress Yamanaka factors upon doxycycline administration and carries the Tau-P301S mutation, which leads to tauopathy development. The results of this study show a significant improvement in key pathological features of tauopathies in the hippocampus, including reversed tauopathy, alleviated reactive astrogliosis, age-related reduction of the H3K9me3 epigenetic marker, along with improved spatial memory, which has been described as deteriorated in this model. These findings reinforce the potential of partial reprogramming as a therapeutic strategy to combat brain pathologies associated with aging.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102743"},"PeriodicalIF":6.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531861","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}

{"title":"Reactivated thalamocortical plasticity alters neural activity in sensory-motor cortex during post-critical period","authors":"Hyesoo Jie ,&nbsp;Emily Petrus ,&nbsp;Nikorn Pothayee ,&nbsp;Alan P. Koretsky","doi":"10.1016/j.pneurobio.2025.102735","DOIUrl":"10.1016/j.pneurobio.2025.102735","url":null,"abstract":"<div><div>Neuroplasticity in sensory brain areas supports adaptation after nerve injury and fundamentally impacts sensation and movement. However, limited neuroplasticity in somatosensory areas due to the early critical period makes determining the role of thalamocortical (TC) inputs in sensorimotor signal processing challenging. Here, we demonstrated that reactivation of TC neuroplasticity was associated with an increase in the number of neurons in layer IV (L4) of the whisker primary somatosensory cortex (wS1) with a stable excitation-inhibition ratio. Highly synchronized neural activity in L4 propagated throughout the wS1 column and to the downstream areas, including whisker secondary somatosensory, primary motor cortices, and contralateral wS1. These results provide crucial evidence that TC inputs can alter the neural activity of sensory-motor pathways even after the critical period. Altogether, these enormous changes in sensorimotor circuit activity are important for adaptation following an injury such as limb loss, stroke, or other forms of neural injury.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102735"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511880","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}

{"title":"Single-cell RNA sequencing reveals ECM remodeling-tumor stiffness-FAK as a key driver of vestibular schwannoma progression","authors":"Yu Zhang ,&nbsp;Jianfei Long ,&nbsp;Jian Xu ,&nbsp;Ping Zhong ,&nbsp;Bin Wang","doi":"10.1016/j.pneurobio.2025.102730","DOIUrl":"10.1016/j.pneurobio.2025.102730","url":null,"abstract":"<div><div>Vestibular schwannoma (VS), characterized by the absence of merlin expression, is the most prevalent benign tumor located at the cerebellopontine angle, lacking approved pharmaceutical interventions except for off-label utilization of bevacizumab. The role of Tumor stiffness-Focal adhesion kinase (FAK) activation in fueling tumor progression is well-established, with merlin deficiency serving as a biomarker for tumor sensitivity to FAK inhibitors. In this context, we investigated whether Tumor stiffness-FAK contributes to VS progression. Single-cell RNA sequencing revealed associations between VS progression and gene sets related to “Response to mechanical stimulus” and “Neurotrophin signaling pathway”. Histological studies indicated a potential involvement of neurotrophins in early stages of VS tumorigenesis, while enhanced Extracellular matrix (ECM) remodeling-Tumor stiffness-FAK signaling accompanies later stages of VS progression. <em>In vitro</em> experiments demonstrated that elevated matrix stiffness induces cytoskeletal remodeling, cell proliferation, and metalloproteinase expression in VS cells by activating FAK. Conversely, FAK inhibition diminishes these effects. Collectively, this study suggests that ECM remodeling-Tumor stiffness contributes to VS progression via FAK activation, positioning FAK as a promising therapeutic target in treating VS.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102730"},"PeriodicalIF":6.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479472","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}

{"title":"Increased seizure susceptibility in thyroid hormone transporter Mct8/Oatp1c1 knockout mice is associated with altered neurotransmitter systems development","authors":"Andrea Alcaide Martin ,&nbsp;Reinhard Bauer ,&nbsp;Dagmar Führer-Sakel ,&nbsp;Heike Heuer ,&nbsp;Steffen Mayerl","doi":"10.1016/j.pneurobio.2025.102731","DOIUrl":"10.1016/j.pneurobio.2025.102731","url":null,"abstract":"<div><div>Thyroid hormone (TH) transporters such as the monocarboxylate transporter Mct8 and the organic anion transporting protein Oatp1c1 facilitate TH transport into target cells. In humans, inactivating mutations in MCT8 result in Allan-Herndon-Dudley syndrome (AHDS), a severe psychomotor retardation with hallmarks of a central TH deficit and frequently observed seizures of unknown etiology. Here, we aimed to investigate seizure susceptibility in AHDS by using Mct8/Oatp1c1 double-knockout (Dko) mice, a well-established AHDS model. We tested seizure susceptibility using the pilocarpine model and observed a significantly faster occurrence of status epilepticus (SE) and more severe responses to seizure induction in Dko animals. We analyzed neuronal alterations in the hippocampus, an area central in seizure pathology, 12 h after SE by immuno-fluorescence and in situ hybridization (ISH). Dko mice presented increased cFos immunoreactivity, and ectopic expression of somatostatin in CA3 neurons. To unravel underlying mechanisms, we studied neurotransmitter systems in murine hippocampi during development at P12 and in adulthood. Employing immuno-fluorescence, ISH and qPCR analyses, we revealed an abnormal development of the inhibitory GABAergic, excitatory glutamatergic and cholinergic systems in Dko mice. Together, our data point to an altered inhibition/excitation balance in the Dko hippocampus that may explain the increased seizure susceptibility.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102731"},"PeriodicalIF":6.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477095","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}

{"title":"The correct connectivity of the DG-CA3 circuits involved in declarative memory processes depends on Vangl2-dependent planar cell polarity signaling","authors":"Noémie Depret ,&nbsp;Marie Gleizes ,&nbsp;Maïté Marie Moreau ,&nbsp;Sonia Poirault-Chassac ,&nbsp;Anne Quiedeville ,&nbsp;Steve Dos Santos Carvalho ,&nbsp;Vasika Venugopal ,&nbsp;Alice Shaam Al Abed ,&nbsp;Jérôme Ezan ,&nbsp;Gael Barthet ,&nbsp;Christophe Mulle ,&nbsp;Aline Desmedt ,&nbsp;Aline Marighetto ,&nbsp;Claudia Racca ,&nbsp;Mireille Montcouquiol ,&nbsp;Nathalie Sans","doi":"10.1016/j.pneurobio.2025.102728","DOIUrl":"10.1016/j.pneurobio.2025.102728","url":null,"abstract":"<div><div>In the hippocampus, dentate gyrus granule cells connect to CA3 pyramidal cells via their axons, the mossy fibers (Mf). The synaptic terminals of Mfs (Mf boutons, MfBs) form large and complex synapses with thorny excrescences (TE) on the proximal dendrites of CA3 pyramidal cells (PCs). MfB/TE synapses have distinctive “detonator” properties due to low initial release probability and large presynaptic facilitation. The molecular mechanisms shaping the morpho-functional properties of MfB/TE synapses are still poorly understood, though alterations in their morphology are associated with Down syndrome, intellectual disabilities, and Alzheimer’s disease. Here, we identify the core PCP gene <em>Vangl2</em> as essential to the morphogenesis and function of MfB/TE synapses. Vangl2 colocalises with the presynaptic heparan sulfate proteoglycan glypican 4 (GPC4) to stabilise the postsynaptic orphan receptor GPR158. Embryonic loss of Vangl2 disrupts the morphology of MfBs and TEs, impairs ultrastructural and molecular organisation, resulting in defective synaptic transmission and plasticity. In adult, the early loss of Vangl2 results in a number of hippocampus-dependent memory deficits including characteristic flexibility of declarative memory, organisation and retention of working / everyday-like memory. These deficits also lead to abnormal generalisation of memories to salient cues and diminished ability to form detailed contextual memories. Together, these results establish Vangl2 as a key regulator of DG-CA3 connectivity and functions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"246 ","pages":"Article 102728"},"PeriodicalIF":6.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433567","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}

{"title":"Cyto-, gene, and multireceptor architecture of the early postnatal mouse hippocampal complex","authors":"Ling Zhao ,&nbsp;Menno P. Witter ,&nbsp;Nicola Palomero-Gallagher","doi":"10.1016/j.pneurobio.2024.102704","DOIUrl":"10.1016/j.pneurobio.2024.102704","url":null,"abstract":"<div><div>Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative <em>in vivo</em> receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes. We provide a novel and comprehensive characterization of the cyto-, gene, and multireceptor architecture of the developing mouse hippocampal and subicular regions during the developmental period, which typically differs from that in the adult brain. High-density receptor expressions with distinct regional and laminar distributions were observed for AMPA, Kainate, mGluR2/3, GABA_A, GABA_A/BZ, α₂, and A₁ receptors during this specific period, whereas NMDA, GABA_B, α₁, M₁, M₂, M₃, nicotinic α₄β₂, 5-HT_1A, 5-HT₂, D₁ and D₂/D₃ receptors exhibited relatively low and homogeneous expressions. This specific balance of multiple receptors aligns with regional cytoarchitecture, neurotransmitter distributions, and gene expressions. Moreover, contrasting with previous findings, we detected a high α₂ receptor density, with distinct regional and laminar distribution patterns. A non-covariation differentiation phenomenon between α₂ receptor distributions and corresponding gene expressions is also demonstrated in this early developmental period. The multimodal data provides new insights into understanding the hippocampal development from the perspective of cell, gene, and multireceptor levels, and contributes important resources for further interdisciplinary analyses.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"245 ","pages":"Article 102704"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872814","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}

{"title":"Social odors drive hippocampal CA2 place cell responses to social stimuli","authors":"Emma Robson ,&nbsp;Margaret M. Donahue ,&nbsp;Alexandra J. Mably ,&nbsp;Peyton G. Demetrovich ,&nbsp;Lauren T. Hewitt ,&nbsp;Laura Lee Colgin","doi":"10.1016/j.pneurobio.2024.102708","DOIUrl":"10.1016/j.pneurobio.2024.102708","url":null,"abstract":"<div><div>Hippocampal region CA2 is essential for social memory processing. Interaction with social stimuli induces changes in CA2 place cell firing during active exploration and sharp wave-ripples during rest following a social interaction. However, it is unknown whether these changes in firing patterns are caused by integration of multimodal social stimuli or by a specific sensory modality associated with a social interaction. Rodents rely heavily on chemosensory cues in the form of olfactory signals for social recognition processes. To determine the extent to which social olfactory signals contribute to CA2 place cell responses to social stimuli, we recorded CA2 place cells in rats freely exploring environments containing stimuli that included or lacked olfactory content. We found that CA2 place cell firing patterns significantly changed only when social odors were prominent. Also, place cells that increased their firing in the presence of social odors alone preferentially increased their firing during subsequent sharp wave-ripples. Our results suggest that social olfactory cues are essential for changing CA2 place cell firing patterns during and after social interactions. These results support prior work suggesting CA2 performs social functions and shed light on processes underlying CA2 responses to social stimuli.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"245 ","pages":"Article 102708"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915351","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}