FTO (fat-mass and obesity-associated protein) deficiency aggravates age-dependent depression-like behaviors and cognitive impairment DOI Open Access
Mengdie Li, Yating Yang, Tangcong Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Abstract Background The demethylase fat mass and obesity-related protein (FTO) is strongly associated with depression. Aging a risk factor for synaptic plasticity damage in the brain leads to neurocognitive dysfunctions. However, whether FTO susceptibility depression different age groups remains unknown. Methods We subjected 3-and 12-month-old C57BL/6J male mice 6 weeks of chronic unpredictable mild stress (CUMS) 3 hippocampal injection knockdown adeno-associated virus 9 shRNA (FTO-KD AAV9). Finally, 36 each 3-month-old were divided into three (n=12): Sham, CUMS, FTO-KD. After weeks, we assessed behavioral deficits (depressive anxiety-like behaviors cognitive impairment) by tests neuronal (dendritic spine density, atrophy, expression proteins plasticity) molecular biochemical experiments. Results results showed that more likely develop depression-like behavior spatial learning memory impairment induced CUMS than mice. Chronic stress-induced worsened after FTO-KD intervention. In hippocampus mice, downregulation FTO, nerve growth (NGF), reelin, plasticity-related proteins. It also caused abnormal BDNF-TrkB signaling, reduced density dendritic spines, an increased number pyknotic nuclei, leading disarray, which was significant animals. deficiency accelerated Conclusions This study provides rodent evidence may increase older adults impairing function age-dependent manner. suggests development activators be effective treatment adults.

Language: Английский

Schaftoside Reduces Depression- and Anxiogenic-like Behaviors in Mice Depression Models DOI Creative Commons

Hu Yue,

Yaoxue Gan,

Lei Jia

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 238 - 238

Published: Feb. 24, 2025

Background: Major depressive disorder is a common mental health issue characterized by persistently low mood and high morbidity mortality. The major pathophysiology neuroinflammation, as evidenced elevated cytokine levels. Patients often fail to achieve full remission with the use of currently available antidepressants, prompting search for new treatment options. Schaftoside (SS), flavonoid found in traditional Chinese herbs, has both antioxidant anti-inflammatory properties. However, its antidepressant effects are poorly understood. Methods: Male C57BL/6 mice underwent chronic unpredictable mild stress (CUMS) lipopolysaccharide (LPS) induce depression- anxiety-like behaviors. SS was administered at 40, 80, 160 mg/kg 28 days. effect on depression-like behaviors assessed using behavioral assays, ELISA used measure pro-inflammatory cytokines serum hippocampus. Results: significantly decreased immobility forced swim tail suspension tests, increased sucrose preference test, reduced feeding latency novelty-suppressed test. These findings indicate improved depression showed that lowered interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha levels hippocampus CUMS mice. Conclusions: Our study indicates anxiolytic effects, possibly through neuroinflammatory processes, making it promising therapeutic candidate depression, thus deserves further investigation into mechanisms clinical efficacy.

Language: Английский

Citations

0

Effects of Black Rice Anthocyanin Extract on Depression-Like Behavior in Chronic Unpredictable Mild Stress Model Mice DOI Creative Commons

Aoran Yuan,

Jianjun Chen, Ying Zhai

et al.

Scientific Journal of Technology, Journal Year: 2024, Volume and Issue: 6(11), P. 63 - 67

Published: Nov. 21, 2024

Objective: To investigate the effects of black rice anthocyanins extract (BSE) on depression-like behavior in mice with chronic unpredictable mild stress (CUMS). Methods: A total 30 male Kunming were randomly divided into Control group, model group (CUMS) and anthocyanin (300 mg/kg). Except blank all treated CUMS to induce depression. After 21 days intragastric administration, behavioral changes analyzed by body weight, sucrose preference test, open field water maze test. Enzyme-linked immunosorbent assay (ELISA) was used detect levels corticotropin-releasing hormone (CRH), adrenocorticotropic (ACTH) corticosterone (CORT). Hematoxylin-eosin staining (HE) observe pathological neurons hippocampal CA1 CA3 regions. Cell apoptosis hippocampus detected terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling (TUNEL) staining. Results: Compared brown-rice treatment showed significantly increased preference, horizontal movement distance vertical standing times decreased escape latency residence time target quadrant number crossing platform, alleviated damage neurons. Plasma ACTH, CORT, CRH decreased, rates decreased. Conclusion: Black have a significant antidepressant effect possibly regulating function HPA axis.

Language: Английский

Citations

0

FTO (fat-mass and obesity-associated protein) deficiency aggravates age-dependent depression-like behaviors and cognitive impairment DOI Open Access
Mengdie Li, Yating Yang, Tangcong Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Abstract Background The demethylase fat mass and obesity-related protein (FTO) is strongly associated with depression. Aging a risk factor for synaptic plasticity damage in the brain leads to neurocognitive dysfunctions. However, whether FTO susceptibility depression different age groups remains unknown. Methods We subjected 3-and 12-month-old C57BL/6J male mice 6 weeks of chronic unpredictable mild stress (CUMS) 3 hippocampal injection knockdown adeno-associated virus 9 shRNA (FTO-KD AAV9). Finally, 36 each 3-month-old were divided into three (n=12): Sham, CUMS, FTO-KD. After weeks, we assessed behavioral deficits (depressive anxiety-like behaviors cognitive impairment) by tests neuronal (dendritic spine density, atrophy, expression proteins plasticity) molecular biochemical experiments. Results results showed that more likely develop depression-like behavior spatial learning memory impairment induced CUMS than mice. Chronic stress-induced worsened after FTO-KD intervention. In hippocampus mice, downregulation FTO, nerve growth (NGF), reelin, plasticity-related proteins. It also caused abnormal BDNF-TrkB signaling, reduced density dendritic spines, an increased number pyknotic nuclei, leading disarray, which was significant animals. deficiency accelerated Conclusions This study provides rodent evidence may increase older adults impairing function age-dependent manner. suggests development activators be effective treatment adults.

Language: Английский

Citations

0