scholarly journals Effects of Long-term Social Isolation on Central, Behavioural and Metabolic Parameters in Middle-Aged Mice

2021 ◽  
pp. 113630
Author(s):  
Izabelle Dias Benfato ◽  
Ana Carolina Silvares Quintanilha ◽  
Jessica Salles Henrique ◽  
Melyssa Alves Souza ◽  
Barbara dos Anjos Rosário ◽  
...  
Keyword(s):  
Social Isolation ◽  
Metabolic Parameters ◽  
Middle Aged ◽  
Aged Mice

scholarly journals Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice

2019 ◽  
Author(s):  
Rand S. Eid ◽  
Stephanie E. Lieblich ◽  
Sarah J. Wong ◽  
Liisa A.M. Galea
Keyword(s):  
Frontal Cortex ◽  
Chronic Stress ◽  
Ovarian Hormones ◽  
Stress Exposure ◽  
Middle Aged ◽  
Aged Mice ◽  
Ovariectomized Mice ◽  
Ovarian Status ◽  
Immunomodulatory Properties

AbstractOvarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones have immunomodulatory properties. However, how ovarian hormones can influence the inflammatory outcomes of stress exposure is poorly understood. Here, we examined the effects of long-term ovariectomy on the behavioral and neuroinflammatory outcomes of sub-chronic stress exposure in middle-aged mice. Briefly, sham-operated and ovariectomized mice were assigned to non-stress groups or exposed to 6 days of variable stress. Mice were assessed on a battery of behavioral tests, and cytokine concentrations were quantified in the frontal cortex and hippocampus. In the frontal cortex, postsynaptic density protein-95 expression was examined as an index of excitatory synapse number and/or stability, and phosphorylated mitogen-activated protein kinases (MAPKs) were measured to explore potential cell signaling pathways elicited by stress exposure and/or ovarian hormones. Long-term ovariectomy modified the central cytokine profile by robustly reducing cytokine concentrations in the frontal cortex and modestly increasing concentrations in the hippocampus. Under non-stress conditions, long-term ovariectomy also reduced extracellular signal-regulated kinase (ERK) phosphoprotein expression in the frontal cortex and increased some measures of depressive-like behavior. The effects of sub-chronic stress exposure were however more pronounced in sham-operated mice. Notably, in sham-operated mice only, sub-chronic stress exposure increased IL-1β and IL-6:IL-10 ratio in the frontal cortex and hippocampus and reduced pERK1/2 expression in the frontal cortex. Further, although sub-chronic stress exposure increased anhedonia-like behavior regardless of ovarian status, it increased passive-coping behavior in sham-operated mice only. These data indicate that long-term ovariectomy has potent effects on the central cytokine milieu and dictates the neuroinflammatory and behavioral effects of sub-chronic stress exposure in middle-aged mice. These findings therefore suggest that the immunomodulatory properties of ovarian hormones are of relevance in the context of stress and possibly depression.

scholarly journals Impaired Cognitive Function and Hippocampal Changes Following Chronic Diazepam Treatment in Middle-Aged Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Tomonori Furukawa ◽  
Yoshikazu Nikaido ◽  
Shuji Shimoyama ◽  
Nozomu Masuyama ◽  
Ayaka Notoya ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Adverse Effects ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Density ◽  
Middle Aged ◽  
Aged Mice ◽  
Dendritic Spine Density ◽  
Young Mice

Background: Gamma-aminobutyric acid (GABA) type A receptors are positively allosterically modulated by benzodiazepine binding, leading to a potentiated response to GABA. Diazepam (DZP, a benzodiazepine) is widely prescribed for anxiety, epileptic discharge, and insomnia, and is also used as a muscle relaxant and anti-convulsant. However, some adverse effects – such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning – are elicited by the long-term use of DZP. Clinical studies have reported that chronic DZP treatment increases the risk of dementia in older adults. Furthermore, several studies have reported that chronic DZP administration may affect neuronal activity in the hippocampus, dendritic spine structure, and cognitive performance. However, the effects of chronic DZP administration on cognitive function in aged mice is not yet completely understood.Methods: A behavioral test, immunohistochemical analysis of neurogenic and apoptotic markers, dendritic spine density analysis, and long-term potentiation (LTP) assay of the hippocampal CA1 and CA3 were performed in both young (8 weeks old) and middle-aged (12 months old) mice to investigate the effects of chronic DZP administration on cognitive function. The chronic intraperitoneal administration of DZP was performed by implanting an osmotic minipump. To assess spatial learning and memory ability, the Morris water maze test was performed. Dendritic spines were visualized using Lucifer yellow injection into the soma of hippocampal neurons, and spine density was analyzed. Moreover, the effects of exercise on DZP-induced changes in spine density and LTP in the hippocampus were assessed.Results: Learning performance was impaired by chronic DZP administration in middle-aged mice but not in young mice. LTP was attenuated by DZP administration in the CA1 of young mice and the CA3 of middle-aged mice. The spine density of hippocampal neurons was decreased by chronic DZP administration in the CA1 of both young and middle-aged mice as well as in the CA3 of middle-aged mice. Neither neurogenesis nor apoptosis in the hippocampus was affected by chronic DZP administration.Conclusion: The results of this study suggest that the effects of chronic DZP are different between young and middle-aged mice. The chronic DZP-induced memory retrieval performance impairment in middle-aged mice can likely be attributed to decreased LTP and dendritic spine density in hippocampal neurons in the CA3. Notably, prophylactic exercise suppressed the adverse effects of chronic DZP on LTP and spine maintenance in middle-aged mice.

Sign in / Sign up

Export Citation Format

Share Document