scholarly journals Sex differences in chronic social stress models in mice

2019 ◽  
Author(s):  
Orit Furman ◽  
Michael Tsoory ◽  
Alon Chen
Keyword(s):  
Sex Differences ◽  
Animal Models ◽  
Mouse Model ◽  
Treatment Response ◽  
Chronic Stress ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Body Weight Loss ◽  
Chronic Social Stress

AbstractChronic stress creates an allostatic overload that may lead to mood disorders such as anxiety and depression. Modern causes of chronic stress in humans are mostly social in nature, relating to work and relationship stress. Research into neural and molecular mechanisms of vulnerability and resilience following chronic social stress (CSS) is ongoing and uses animal models to discover efficient prevention strategies and treatments. To date, most CSS studies have neglected the female sex and used male-focused aggression-based animal models such as chronic social defeat stress (CSDS). Accumulating evidence on sex differences suggests differences in the stress response, the prevalence of stress-related illness and the treatment response, indicating that researchers should expand CSS investigation to include female-focused protocols alongside the popular CSDS protocols. Here, we describe a novel female mouse model of CSS and a parallel modified male mouse model of CSDS in C57BL/6 mice. These new models enable the investigation of vulnerability, coping and downstream effectors mediating long-term consequences of CSS in both sexes. Our data demonstrate sex differences during CSS and for many weeks following CSS. Female mice are more prone to body weight loss during CSS and hyperactive anxious behavior following CSS. Both sexes show disturbances in social interaction, but only stressed male mice show long-term changes in neuroendocrine function and memory performance after fear conditioning. We discuss future avenues of research using these models to investigate mechanisms pertaining to sensitivity to CSS as well as treatment response profiles, in a sex-suitable manner.

scholarly journals miR-98-5p plays a critical role in depression and antidepressant effect of ketamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaoli Huang ◽  
Yuanyuan Wang ◽  
Zifeng Wu ◽  
Jiali Xu ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Rapid Onset ◽  
Therapeutic Strategies ◽  
Antidepressant Effect ◽  
Depression Treatment ◽  
Chronic Social Stress ◽  
Beneficial Effects

AbstractKetamine has been demonstrated to be a rapid-onset and long-lasting antidepressant, but its underlying molecular mechanisms remain unclear. Recent studies have emerged microRNAs as important modulators for depression treatment. In this study, we report that miR-98-5p is downregulated in the prefrontal cortex and hippocampus of mice subjected to chronic social stress, while overexpressing it by its agonist alleviates depression-like behaviors. More importantly, we demonstrate that miR-98-5p is upregulated by ketamine administration, while inhibition of it by its antagonist blocks the antidepressant effect of ketamine. Our data implicate a novel molecular mechanism underlying the antidepressant effect of ketamine, and that therapeutic strategies targeting miR-98-5p could exert beneficial effects for depression treatment.

scholarly journals Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Gonzalo Ruiz-Pérez ◽  
Samuel Ruiz de Martín Esteban ◽  
Sharai Marqués ◽  
Noelia Aparicio ◽  
M. Teresa Grande ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Synaptic Transmission ◽  
Amyloid Beta ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Genetic Inactivation ◽  
5Xfad Mouse

Abstract Background The complex pathophysiology of Alzheimer’s disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. Methods In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse− model. Results We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3–CA1 synapse, both basal synaptic transmission and long-term potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron–glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH−/− animals. Conclusion In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer’s disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the disease.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence

2015 ◽  
Vol 76 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Fábio C. Cruz ◽  
Josiane O. Duarte ◽  
Rodrigo M. Leão ◽  
Luiz F.V. Hummel ◽  
Cleopatra S. Planeta ◽  
...  
Keyword(s):  
Social Isolation ◽  
Social Stress ◽  
Long Term Effects ◽  
Chronic Social Stress

Behavioral and hormonal effects of prolonged Sildenafil treatment in a mouse model of chronic social stress

2020 ◽  
Vol 392 ◽  
pp. 112707
Author(s):  
H. Dadomo ◽  
D. Ponzi ◽  
Y. Nicolini ◽  
A. Vignali ◽  
F. Ablondi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Social Stress ◽  
Chronic Social Stress ◽  
Hormonal Effects

scholarly journals Androgenic Influences on Behavior, Body Weight, and Body Composition in a Model of Chronic Social Stress

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 6145-6156 ◽  
Author(s):  
Mary M. N. Nguyen ◽  
Kellie L. K. Tamashiro ◽  
Susan J. Melhorn ◽  
Li Y. Ma ◽  
Stacy R. Gardner ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Composition ◽  
Body Weight ◽  
Adipose Tissue ◽  
Social Stress ◽  
Body Weight Loss ◽  
Oral Glucose ◽  
Lean Tissue ◽  
Chronic Social Stress ◽  
And Control

The visible burrow system (VBS) is a model used to study chronic social stress in colony-housed rats. A hierarchy develops among the males resulting in dominant (DOM) and subordinate (SUB) animals. Hierarchy-associated changes in body weight, body composition, behavior, and neuroendocrine measures have been observed. After 14 d of VBS housing, SUB animals have decreased body weight, elevated corticosterone, and decreased testosterone (T), compared with DOM animals and controls, placing SUB animals in an ideal endocrine state to regain lost body weight as adipose tissue. It is hypothesized that maintaining constant androgen concentrations in SUB males during stress will prevent body weight loss by maintaining more lean body mass. To test this, animals were gonadectomized and implanted with SILASTIC implants containing T, 5α-dihydrotestosterone (DHT), or cholesterol. Implants maintained constant physiological levels of T. Standard intact, T, and DHT implant colonies formed hierarchies, whereas cholesterol colonies did not. Androgen manipulations significantly altered offensive and defensive behaviors only on the first day of VBS housing. After VBS stress, intact, T, and DHT SUB animals weighed less and lost more adipose and lean tissue than DOM and control males, whereas DOM animals primarily lost adipose tissue. However, on recovery, DHT SUB animals maintained more lean tissue than intact SUB animals. Oral glucose tolerance tests revealed that glucose clears faster in stressed T-implanted males that have increased adipose tissue. Overall, these data suggest that constant androgen concentrations in SUB animals do not prevent weight loss and changes in body composition during stress but do so during recovery.

Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: Implications for stress-related disorders

2008 ◽  
Vol 53 (2) ◽  
pp. 386-394 ◽  
Author(s):  
Vera Sterlemann ◽  
Karin Ganea ◽  
Claudia Liebl ◽  
Daniela Harbich ◽  
Stephanie Alam ◽  
...  
Keyword(s):  
Social Stress ◽  
Chronic Social Stress

scholarly journals Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction

2021 ◽  
Vol 22 (22) ◽  
pp. 12366
Author(s):  
Francesca Chiara Pignalosa ◽  
Antonella Desiderio ◽  
Paola Mirra ◽  
Cecilia Nigro ◽  
Giuseppe Perruolo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Dopaminergic System ◽  
Diabetic Patients ◽  
Comprehensive Overview ◽  
Dopaminergic Dysfunction ◽  
Glycation End Products

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA’s role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.

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