Sex-specific hypothalamic neuropathology and glucose metabolism in an amyloidosis transgenic mouse model of Alzheimer’s disease DOI Creative Commons
Guibo Qi, Han Tang,

Pifang Gong

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 13, 2024

Abstract Background Amyloid toxicity and glucose metabolic disorders are key pathological features during the progression of Alzheimer’s disease (AD). While hypothalamus plays a crucial role in regulating systemic energy balance, distribution amyloid plaques preoptic, anterior, tuberal, mammillary regions AD mice, particularly across both sexes, remains largely unclear. Our ongoing research aims to explore hypothalamic neuropathology disturbances well-described APP/PS1 mouse model AD. Results Immunocytochemical staining revealed that Old-AD-Female mice exhibited greater β (Aβ) burden than their Old-AD-Male counterparts, with bodies showing most severe accumulation. Analysis ionized calcium binding adaptor molecule 1 (IBA1) immunoreactivity Iba1 mRNA indicated differential microgliosis based on sex, while tanycytic territory ZO-1 tight junction protein expression remained stable mice. Moreover, sex-specific peripheral parameters (random fasting blood glucose) seemed be exacerbated by age. Old sexes limited activation (c-Fos + cells) response fluctuations. Hypothalamic Glut decreased young but increased old female compared age-matched male Pearson correlation analysis further supported negative between Aβ load random groups genders, shedding light mechanisms underlying this amyloidosis model. Conclusion Aged exhibit metabolism, highlighting distinct within each gender.

Language: Английский

Depletion of MGO or Its Derivatives Ameliorate CUMS-Induced Neuroinflammation DOI Creative Commons
Bing Liu,

Ke Dong,

Yun Zhao

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 397 - 397

Published: March 8, 2025

Advanced glycation end products (AGEs) are a series of structurally complex and harmful compounds formed through the reaction between carbonyl group reducing sugars (such as glucose fructose) free amino groups proteins, lipids, or nucleic acids. Excessive accumulation AGEs in body can trigger oxidative stress, induce inflammatory responses, contribute to development diabetes, atherosclerosis, neurological disorders. Within category dicarbonyl compounds, methylglyoxal (MGO)—a byproduct resulting from degradation—serves pivotal precursor formation induction neurotoxicity. Specifically, generated MGO display significant cytotoxicity toward cells central nervous system. Therefore, we aimed investigate role MGO-AGEs neuroinflammation mediated by CUMS. Interestingly, found that overexpression glyoxalase 1 (GLO1) reduced levels corticosterone-treated microglia, thereby alleviating response. Furthermore, GLO1 hippocampus chronically stressed mice levels, mitigating CUMS-induced cognitive impairment. Additionally, when using receptor for advanced (RAGE) inhibitor FPS-ZM1 primary microglia cells, observed despite corticosterone-induced elevation MGO, no response occurred. This suggests RAGE clearance reduce MGO-AGE-mediated Subsequently, used treat it significantly ameliorated dysfunction. These results suggest targeting metabolism could serve therapeutic approach manage stress-related mental

Language: Английский

Citations

1
Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research DOI Creative Commons
Eun Sun Jung, Hayoung Choi, Inhee Mook‐Jung

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 27, 2025

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.

Language: Английский

Citations

1
The impact of neuroinflammation on neuronal integrity DOI Open Access
Bora Tastan, Michael T. Heneka

Immunological Reviews, Journal Year: 2024, Volume and Issue: 327(1), P. 8 - 32

Published: Oct. 1, 2024

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, disease pathologies. However, dysregulation of neuroinflammatory response could significantly affect neurons terms function structure, leading profound health implications. Although tremendous progress has been made understanding relationship between processes alterations neuronal integrity, specific implications concerning both structure have not extensively covered, with exception perspectives on glial activation neurodegeneration. Thus, this review aims provide comprehensive overview multifaceted interactions key inflammatory players, exploring mechanisms through which inflammation influences functionality structural integrity CNS. Further, it will discuss how these lead impairment functions architecture highlight consequences caused dysregulated functions, such as cognitive dysfunction mood disorders. By integrating insights from recent research findings, enhance our landscape set stage for future interventions that transform current approaches preserve CNS-related conditions.

Language: Английский

Citations

5
AMPK as a Therapeutic Target: Advancing Epilepsy Management Through Metabolic Modulation DOI
Maanvi Dhureja, Anjana Munshi, Puneet Kumar

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
Exploring the Therapeutic Mechanism of Jianpi Zhidong Decoction on Tourette Syndrome Based on Proteomics and Network Pharmacology DOI Creative Commons
Ning Zhang, Hongxian Zhang, Jianning Guo

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 3139 - 3158

Published: April 1, 2025

To explore the pharmacological effects of Jianpi Zhidong Decoction (JPZDD) on Tourette Syndrome (TS) using proteomics and network pharmacology. Chemical components JPZDD were identified via UPLC-MS/MS. Chronic restraint stress TS model was established by intraperitoneal injection iminodipropionitrile (IDPN) for 1 week with 3 weeks. Sixty male SD rats divided into control, model, Tiapride (Tia), groups. After intervention 28 days, behavioral tests, Nissl staining, Western blot, immunofluorescence, colorimetry, ELISA performed to evaluate JPZDD. Proteomics pharmacology predicted targets, validated blot. alleviated stereotypic behaviors, hippocampal pathology, modulated glucose metabolites (GLU, pyruvate, lactate, ATP). It downregulated GLUT1, GLUT3, HK2, LDHA levels while upregulating PDHA level. Besides, balanced M1/M2 microglial phenotypes, reducing IL-1β IL-6 increasing IL-4 IL-10. UPLC-MS/MS 44 active ingredients 123 targets; revealed differentially expressed proteins. GO/KEGG analysis implicated that PI3K/AKT/mTOR pathway may be molecular target. inhibited PI3K, AKT, mTOR phosphorylation. (16 g·kg⁻¹·d⁻¹) alleviates motor tics, modulates activation metabolism, downregulates pathway, providing a mechanistic basis its therapeutic role in TS.

Language: Английский

Citations

0
Inhibition of Glycolysis Alleviates Chronic Unpredictable Mild Stress-Induced Neuroinflammation and Depression-like Behavior DOI Creative Commons
Bing Liu,

Ke Dong,

Xiaobing Chen

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(11), P. 1098 - 1098

Published: Oct. 30, 2024

Growing evidence suggests that glucose metabolism plays a crucial role in activated immune cells, significantly contributing to the occurrence and development of neuroinflammation depression-like behaviors. Chronic stress has been reported induce microglia activation disturbances hippocampus.

Language: Английский

Citations

2
Chronic stress disturbed the metabolism of homocysteine in mouse hippocampus and prefrontal cortex DOI
Cong Xue, Bing Liu, Yun Zhao

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 563, P. 63 - 73

Published: Nov. 7, 2024

Language: Английский

Citations

2
Penetratin and Mannose-Functionalized Cannabidiol Lipid Nanoparticles Encapsulating the BDNF Gene Reduce Amyloid-Induced Inflammation DOI
Bivek Chaulagain, Jagdish Singh

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 22(1), P. 154 - 167

Published: Nov. 26, 2024

Inflammation is emerging as a critical player in the disease progression of Alzheimer's (AD) by its interaction with amyloid beta plaques feed-forward loop. There also decline nourishment and enriching neurotrophic factor, brain-derived factor (BDNF), brain. Therefore, supplementing brain BDNF gene delivery delivering anti-inflammatory agent, cannabidiol (CBD) this case, to mitigate inflammation-induced cascade offers an attractive treatment strategy. To achieve localization CBD pBDNF, lipid nanoparticles (LNPs) functionalized mannose penetratin were utilized. pBDNF successfully encapsulated LNPs (more than 80%) size less 180 nm, polydispersity index 0.25, zeta potential 23 mV. was released from formulation over period week. The dual-functionalized demonstrated higher cellular uptake expressed significantly amount (

Language: Английский

Citations

2
Sex-specific hypothalamic neuropathology and glucose metabolism in an amyloidosis transgenic mouse model of Alzheimer’s disease DOI Creative Commons
Guibo Qi, Han Tang,

Pifang Gong

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 13, 2024

Abstract Background Amyloid toxicity and glucose metabolic disorders are key pathological features during the progression of Alzheimer’s disease (AD). While hypothalamus plays a crucial role in regulating systemic energy balance, distribution amyloid plaques preoptic, anterior, tuberal, mammillary regions AD mice, particularly across both sexes, remains largely unclear. Our ongoing research aims to explore hypothalamic neuropathology disturbances well-described APP/PS1 mouse model AD. Results Immunocytochemical staining revealed that Old-AD-Female mice exhibited greater β (Aβ) burden than their Old-AD-Male counterparts, with bodies showing most severe accumulation. Analysis ionized calcium binding adaptor molecule 1 (IBA1) immunoreactivity Iba1 mRNA indicated differential microgliosis based on sex, while tanycytic territory ZO-1 tight junction protein expression remained stable mice. Moreover, sex-specific peripheral parameters (random fasting blood glucose) seemed be exacerbated by age. Old sexes limited activation (c-Fos + cells) response fluctuations. Hypothalamic Glut decreased young but increased old female compared age-matched male Pearson correlation analysis further supported negative between Aβ load random groups genders, shedding light mechanisms underlying this amyloidosis model. Conclusion Aged exhibit metabolism, highlighting distinct within each gender.

Language: Английский

Citations

1