Molecular Neurobiology最新文献

{"title":"Association of GRM7 Polymorphisms with Bilateral Auditory Regions Glutamate and Coupling with Glutathione in ARHL Patients.","authors":"Jing Wang, Fuyan Li, Fuxin Ren, Wen Ma, Yuxi Liu, Wenjing Zhang, Xi Li, Yanfei Bi, Qian Xin, Fei Gao","doi":"10.1007/s12035-025-05011-3","DOIUrl":"https://doi.org/10.1007/s12035-025-05011-3","url":null,"abstract":"<p><p>This study aimed to investigate the relationship between GRM7 polymorphisms and the levels of glutamate (Glu) and glutathione (GSH) in bilateral auditory regions (ARs) of ARHL patients. Seventy-eight ARHL patients (mean age, 65.94 years ± 3.37 [SD]; 44 men) and 46 normal hearing (NH) controls (mean age, 65.72 years ± 2.32 [SD]; 28 men) were enrolled. Glu and GSH levels in bilateral ARs of all participants were measured and estimated by using magnetic resonance spectroscopy (MRS) and LCModel. In addition, we collected peripheral venous blood samples from all participants for DNA extraction and investigated polymorphisms in the GRM7 gene using TaqMan SNP genotyping. The results showed that Glu and GSH levels in bilateral ARs were significantly lower in GRM7 high-risk group compared with GRM7 low-risk group, regardless of disease status (all p_glu < 0.001; all p_gsh = 0.001). Furthermore, GRM7 low-risk ARHL group had lower Glu levels in bilateral ARs than GRM7 low-risk NH group, whereas no difference was observed between NH and ARHL groups in high-risk (all p_glu < 0.05; all p_glu > 0.05). Finally, we found that Glu and GSH levels were positively correlated only in the low-risk NH group (r_left = 0.536 p = 0.007; r_right = 0.545 p = 0.006). The glutamatergic dysfunction in ARs may be associated with GRM7 polymorphisms, and redox reactions are involved in regulating the glutamatergic abnormalities. The TT genotype of GRM7 rs11928865 SNP is more vulnerable to damage from the antioxidant and the glutamatergic system.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010095","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":"Assessing the Implications of Morphine-Induced Dysregulation of Autophagy on Brain Health.","authors":"Jonaid Ahmad Malik, Javed N Agrewala","doi":"10.1007/s12035-025-05039-5","DOIUrl":"https://doi.org/10.1007/s12035-025-05039-5","url":null,"abstract":"<p><p>Morphine has been a widely used drug for pain management and anesthesia in clinical settings for centuries and is also a drug of abuse. Its illicit use by individuals with substance use disorders has resulted in numerous brain-related complications. The immunopharmacology of morphine is highly complex, necessitating a deeper understanding of its interactions with brain regions involved in learning and memory. Autophagy is a conserved physiological recycling process that degrades cytoplasmic organelles and proteins, repurposing their components for cellular function. However, recent studies indicate that morphine exposure disrupts autophagic processes, contributing to many morphine-associated complications. This article highlights recent advancements in understanding the interplay between morphine and autophagy. By exploring this intricate relationship, we aim to enhance our knowledge of morphine-associated complications and autophagy dysregulation, potentially improving the management of morphine use disorder and related conditions, thereby promoting healthier outcomes.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032989","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":"Regulatory Mechanism of CRTC1 on Autophagy and GluA2 Expression in Epilepsy.","authors":"Xueying Wang, Liqian Zhou, Lin Yang, Shaoping Huang, Yuying Wang, Dan Li","doi":"10.1007/s12035-025-04971-w","DOIUrl":"https://doi.org/10.1007/s12035-025-04971-w","url":null,"abstract":"<p><p>The objective of this study was to elucidate the molecular mechanisms by which cAMP-regulated transcription coactivator1 (CRTC1) regulates autophagy and GluA2 expression in patients with epilepsy.</p><p><strong>Methods: </strong>We initially established a magnesium-free epilepsy cell model and recorded cellular discharges using the whole-cell patch clamp technique. Next, we experimentally activated autophagy and identified effective methods for silencing the CRTC1 gene using RNA interference technology. Furthermore, we developed an animal models of status epilepticus and employed immunofluorescence and Western Blot to elucidate CRTC1's role in regulating autophagy-related genes and GluA2 expression in epilepsy.</p><p><strong>Results: </strong>We observed mouse hippocampal neurons under magnesium-free extracellular conditions. Treatment with an autophagy activator decreased GluA2 expression; however, CRTC1 was not dephosphorylated. CRTC1 siRNA suppressed LC3 and PSD95 expression, whereas CRTC1 siRNA intervention restored GluA2 expression.</p><p><strong>Conclusion: </strong>CRTC1 indirectly influences the expression of synaptic-related proteins and GluA2 by directly modulating autophagy during the pathological process of epilepsy. The findings of this study reveal novel molecular targets for the treatment of epilepsy.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003885","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":"Lacosamide Is a Novel Drug That Improves AGTPBP1 Knockout-Mediated Impairment of Neuronal and Dopaminergic Function.","authors":"Hsin-Pei Wang, Shekhar Singh, Lee-Chin Wong, Chia-Jui Hsu, Shih-Chi Li, Shyh-Jye Lee, Chia-Hwa Lee, Wang-Tso Lee","doi":"10.1007/s12035-025-05016-y","DOIUrl":"https://doi.org/10.1007/s12035-025-05016-y","url":null,"abstract":"<p><p>AGTPBP1 regulates microtubule stabilization through post-translational modification of alpha-tubulin. Mutations in the AGTPBP1 gene are associated with clinical phenotypes such as early postnatal cerebellar atrophy, ataxia, spasticity, and dystonia, highlighting its critical roles in both neurodevelopment and neurodegeneration. However, how AGTPBP1 affects neurite development and its function in dopaminergic neurons remains unclear. To investigate the role of AGTPBP1, we utilized both in vitro AGTPBP1 knockout (KO) cell models and zebrafish models. Our findings reveal that AGTPBP1 KO in cells leads to excessive neurite outgrowth and significantly increases expression of collapsin response mediator protein 2 (CRMP2). Additionally, AGTPBP1 KO results in mitochondrial dysfunction and a hyperdopaminergic state in differentiated neurons. In zebrafish, knockdown of AGTPBP1 caused reduced brain volume and impaired swimming behavior, indicating disrupted neurodevelopment and motor function. Given CRMP2's involvement in both cytoskeletal dynamics and mitochondrial activity, we tested lacosamide, a drug known to modulate CRMP2 expression and phosphorylation. Lacosamide treatment in vitro improved cell morphology and restored mitochondrial function, while in vivo, it rescued brain volume deficits and enhanced swimming performance in AGTPBP1-deficient zebrafish. In conclusion, AGTPBP1 knockout impairs neuronal differentiation, induces mitochondrial dysfunction, increases oxidative stress, and promotes a hyperdopaminergic state. Our study suggests that elevated CRMP2 expression may underlie the pathophysiology of cerebellar degeneration in AGTPBP1-related disorders. Targeting CRMP2 with lacosamide represents a promising therapeutic strategy for mitigating AGTPBP1-mediated neurodegeneration.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001909","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":"Exploring Exosome-Based Approaches for Early Diagnosis and Treatment of Neurodegenerative Diseases.","authors":"Vibhav Varshney, Baneen C Gabble, Ashok Kumar Bishoyi, Pooja Varma, Sarraa Ahmad Qahtan, Aditya Kashyap, Rajashree Panigrahi, Deepak Nathiya, Ashish Singh Chauhan","doi":"10.1007/s12035-025-05026-w","DOIUrl":"https://doi.org/10.1007/s12035-025-05026-w","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs), like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), present an increasingly significant global health burden, primarily due to the lack of effective early diagnostic tools and treatments. Exosomes-nano-sized extracellular vesicles secreted by nearly all cell types-have emerged as promising candidates for both biomarkers and therapeutic agents in NDs. This review examines the biogenesis, molecular composition, and diverse functions of exosomes in NDs. Exosomes play a crucial role in mediating intercellular communication. They are capable of reflecting the biochemical state of their parent cells and have the ability to cross the blood-brain barrier (BBB). In doing so, they facilitate the propagation of pathological proteins, such as amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn), while also enabling the targeted delivery of neuroprotective compounds. Recent advancements in exosome isolation and engineering have opened up new possibilities for diagnostic and therapeutic strategies. These range from the discovery of non-invasive biomarkers to innovative approaches in gene therapy and drug delivery systems. However, challenges related to standardization, safety, and long-term effects must be addressed before exosomes can be translated into clinical applications. This review highlights both the promising potential and the obstacles that must be overcome to leverage exosomes in the treatment of NDs and the transformation of personalized medicine.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971912","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":"Roles for Exosomes from Various Cellular Sources in Spinal Cord Injury.","authors":"Wangnan Mao, Xinghao Liu, Chen Chen, Tongfu Luo, Zheng Yan, Lianguo Wu, Zhongcheng An","doi":"10.1007/s12035-025-05040-y","DOIUrl":"https://doi.org/10.1007/s12035-025-05040-y","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a severe disorder characterized by regeneration challenges in the central nervous system (CNS), resulting in permanent paralysis, loss of sensation, and abnormal autonomic functions. The complex pathophysiology of SCI poses challenges to traditional treatments, highlighting the urgent need for novel treatment approaches. Exosomes have emerged as promising candidates for SCI therapy because of their ability to deliver a wide range of bioactive molecules, such as RNAs, proteins, and lipids, to target cells with minimal immunogenicity, which contribute to anti-inflammatory, anti-apoptotic, autophagic, angiogenic, neurogenic, and axon remodeling activities. In this study, we classified exosomes from different sources into four categories based on the characteristics of the donor cells (mesenchymal stem cells, neurogenic cells, immune cells, vascular-associated cells) and provided a detailed summary and discussion of the current research progress and future directions for each source. We also conducted an in-depth investigation into the applications of engineered exosomes in SCI therapy, focusing on their roles in drug delivery and combination with surface engineering technologies and tissue engineering strategies. Finally, the challenges and prospects of exosomal clinical applications in SCI repair are described.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004588","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":"SG06, a Chalcone Derivative Targets PI3K/AKT1 Pathway for Neuroprotection and Cognitive Enhancement in an Alzheimer's Disease-Like Zebrafish Model.","authors":"Santhanam Sanjai Dharshan, Meghana R, Shreya Madhankumar Rao, B Aswinanand, Karthikeyan Ramamurthy, Muthumareeswaran Muthuramamoorthy, M Valan Arasu, Kathiravan Muthu Kumaradoss, Ajay Guru, Senthilkumar Palaniappan, Jesu Arockiaraj","doi":"10.1007/s12035-025-05023-z","DOIUrl":"https://doi.org/10.1007/s12035-025-05023-z","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and Alzheimer's dementia (ADM) are common neurodegenerative disorders marked by progressive cognitive decline, memory impairment, and behavioral deficits, which impose a significant burden on individuals and healthcare systems worldwide. Due to the complex nature of AD pathophysiology, effective treatment strategies may require targeting multiple pathways. This study explored the neuroprotective effects of the chalcone derivative SG06 in a scopolamine-induced AD-like zebrafish model using network pharmacology and molecular docking. SG06 showed strong binding to key targets such as AKT serine/threonine kinase 1 (AKT1), which are involved in processes like tau phosphorylation, amyloid-beta (Aβ) production, and inflammation. Behavioral assays indicated that SG06 improved cognitive function, reduced anxiety-like behavior, and restored social interactions. Additionally, sensory recovery was observed through better light/dark transitions and recovered olfactory function, likely due to improved neuronal communication and reduced oxidative stress. Mechanistically, SG06 appeared to activate the PI3K/AKT1 pathway, inhibiting Glycogen Synthase Kinase 3 beta (GSK3β) activity, which may help reduce tau hyperphosphorylation and amyloid processing. SG06 also restored antioxidant markers (CAT, GSH, GPx) and improved acetylcholinesterase (AChE) activity, reducing oxidative damage and cholinergic dysfunction. Histological analysis revealed improved cellular morphology and decreased Aβ plaque accumulation, while gene expression studies showed downregulation of pro-inflammatory markers and upregulation of neuroprotective genes. Additionally, SG06 helped improving neurotransmitter balance, particularly in Gamma-Aminobutyric Acid (GABA) and Dopamine (DPAN), contributing to improved synaptic plasticity and cognitive function. These findings suggest that SG06 may have potential as a multi-target therapeutic agent in addressing the complex pathology of AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028202","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":"Oral Supplementation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Can Prevent TBI-Induced Visual, Motor, and Emotional Deficits in Mice.","authors":"Koushik Mondal, Ashlyn A Gary, Anisha Dash, Nobel A Del Mar, Daniel J Stephenson, Charles E Chalfant, Anton Reiner, Barry Sears, Nawajes Mandal","doi":"10.1007/s12035-025-05019-9","DOIUrl":"https://doi.org/10.1007/s12035-025-05019-9","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) causes neuroinflammation and can generate long-term pathological consequences, including motor and visual impairments, cognitive deficits, and depression. In our previous study, we found that Fat1⁺-transgenic mice with higher endogenous n-3 polyunsaturated fatty acids (n-3 PUFA) were protected from post-TBI behavioral deficits and exhibited reduced levels of TBI-induced microglial activation, inflammatory factors, and sphingolipid ceramide, a lipid mediator of inflammation and cell death. This study's objective was to evaluate if feeding n-3 PUFA (EPA and docosahexaenoic acid, DHA 2:1) could restrict the elevation of ceramide in brain tissue and prevent TBI-mediated sensory-motor and behavioral deficits. Wildtype C57/BL6 mice were gavage pre-fed with PUFA (EPA: DHA = 2:1) at 500 mg/kg body weight/week for 2 weeks before and 4 weeks after exposure to left side focal cranial air-blast (50 psi) TBI or sham-blast (0-psi). Saline-gavaged mice served as controls. Following blast injury, various motor, visual, and behavioral tests were conducted, and brain tissues were collected for histological and biochemical assays. Lipidomics analysis confirmed a significant elevation of EPA in the plasma and brain tissue of PUFA-fed mice. TBI-Blast brain tissues were found to have elevated ceramide levels in control mice but not in PUFA-fed mice. Moreover, PUFA-fed mice demonstrated protection against motor impairment, photoreceptor dysfunction, depression, oculomotor nerve degeneration, and microglia activation in the optic tract. Our results demonstrate that EPA-mediated suppression of ceramide biosynthesis and neuroinflammatory factors in PUFA-fed mice is associated with significant protection against the visual, motor, and emotional deficits caused by TBI.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028087","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":"Exploring the Connection Between BDNF/TrkB and AC/cAMP/PKA/CREB Signaling Pathways: Potential for Neuroprotection and Therapeutic Targets for Neurological Disorders.","authors":"Abhishek Kumar Gupta, Sumedha Gupta, Sidharth Mehan, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula","doi":"10.1007/s12035-025-05001-5","DOIUrl":"https://doi.org/10.1007/s12035-025-05001-5","url":null,"abstract":"<p><p>The BDNF/TrkB and AC/cAMP/PKA/CREB signaling pathways play a vital role in neuroplasticity, neuronal survival, and cognitive functions. This review explores its physiological and pathological implications in neurological disorders, with a focus on neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs). Neurological conditions increasingly burden public health, making understanding the biochemical mechanisms that underpin these diseases critical. BDNF, a neurotrophic factor, binds to the TrkB receptor, activating multiple intracellular signaling cascades that regulate cellular responses essential for neurogenesis, memory, and learning. Dysregulation within this pathway has been linked to various NDDs, as well as NPDs. Key components of the path, including adenylyl cyclase and cyclic AMP, mediate the effects of neurotransmitters and growth factors, influencing downstream targets like PKA and CREB, which are crucial for gene expression and synaptic changes. Furthermore, the review discusses the challenges of targeting this pathway for therapeutic interventions, including receptor isoform diversity, blood-brain barrier penetration, and potential side effects. Future strategies may include the development of selective TrkB modulators, nanoparticle carriers for drug delivery, and innovative gene therapy techniques. Advancing the understanding of this complex signaling network holds promise for effective interventions in treating neurological and psychiatric disorders, ultimately enhancing neuroprotection and cognitive resilience.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031983","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":"A novel Dual GLP-1/CCK Receptor Agonist Improves Cognitive Performance and Synaptogenesis in the 5 × FAD Alzheimer Mouse Model.","authors":"He Ma, Zhenghui Chang, Hongyu Sun, Dongrui Ma, Zhonghua Li, Li Hao, Zhenqiang Zhang, Christian Hölscher, Zijuan Zhang","doi":"10.1007/s12035-025-05037-7","DOIUrl":"https://doi.org/10.1007/s12035-025-05037-7","url":null,"abstract":"<p><p>Glucagon-like peptide 1 (GLP-1) is a peptide hormone and growth factor. Cholecystokinin (CCK) is another peptide hormone, growth factor and neurotransmitter. Both peptide hormones have shown good neuroprotective effects in animal models of Alzheimer's disease (AD). In this study, we tested the effects of a dual GLP-1/CCK (25 nmol/kg ip. for 14 days) receptor agonist that had previously shown good effects in animal models of diabetes. The GLP-1 analogue Liraglutide (50 nmol/kg ip.) was used as a positive control. Memory was improved in the water maze and the Y-maze, spontaneous activity was increased, the chronic inflammation response had been reduced and levels of NLRP3, IL-10 and TNFα were brought back to physiological levels. Levels of amyloid aggregates in the brain were reduced by the drugs. The expression of proteins SIRPα and CD47 which is related to reduced inflammation levels was reduced. Importantly, growth factor signalling was much improved and growth levels of BDNF, TrkB receptor, p-CREB, and an upregulation of the PI3K-AKT signalling pathway had been observed. Post-synaptic density protein (PSD) and synaptophysin levels were reduced, too. In transmission electron microscope analysis, the synaptic cleft was found to be wider in 5xFAD mice. In Golgi stain evaluations, synapse numbers were brought back to normal levels by the drugs. In a direct comparison with Liraglutide, the dual GLP-1/CCK receptor agonist was superior in the water maze tests and in the upregulation of BDNF and TrkB levels in the brain. In other parameters, the dual agonist and Liraglutide showed comparable effects. In conclusion, the combination of GLP-1 and CCK receptor activation did not show overall improvements over single GLP-1 receptor activation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019780","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}