Abstract W MP50: Pair Housing Reverses the Detrimental Effect of Social Isolation and Restores BDNF and MBP in Aged Mice after Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rajkumar Verma ◽  
Nia Harris ◽  
Brett Friedler ◽  
Joshua Crapser ◽  
Anita Patel ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Western Blot ◽  
Social Isolation ◽  
Enhanced Recovery ◽  
Infarct Volume ◽  
Recognition Task ◽  
Aged Mice ◽  
Post Stroke ◽  
Beneficial Effects ◽  
Novel Object Recognition Task

Background: Age is an important non-modifiable risk factor for stroke. Stroke rates double every decade after age 55. Social isolation (SI) exacerbates behavioural deficits, slows functional recovery and worsens histological injury after stroke in young animals, primarily by increasing the inflammatory response. However, the inflammatory response differs in aging, and whether the detrimental effects of SI are seen in aged animals is unknown. We hypothesize that acute and chronic post stroke SI will worsen stroke pathology and recovery in aged mice and pair housing (PH) will reverse these effects. Methods: Eighteen-month-old male C57BL/6 mice were pair housed (PH) for two weeks prior to stroke and randomly assigned to various housing conditions immediately after stroke. Behavioral analysis was done weekly starting at day 7. Mice were sacrificed either at 72 hours or 4 weeks after 60-minute right MCAO or sham surgery (n=9-10/group). Results: Mice isolated after stroke (ST-ISO) mice had significantly greater hemispheric infarct volume and neurological deficit scores (p<.05. n=13/group) than pair-housed (PH) stroke mice at 72 hours. SI mice that were isolated immediately after stroke showed significantly higher plasma IL-6 levels compared to PH sham (P<.001, n=13/group ) or PH stroke mice (P<.05) after 72 hour, but levels were similar by 4 weeks post-stroke (n=9-14/group). No change in tissue atrophy was seen after 4 weeks, however a significant interaction [F (1, 28) = 259.6, P<0.001] between housing and stroke was found in the Novel Object Recognition Task (NORT) at day 14. PH led to increased expression of Brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP) by IHC and western blot (n=5/group for IHC and n= 4/ western blot). Conclusions: Social isolation immediately after stroke led to enhanced injury acutely. Despite similar infarcts at 4 weeks, SI mice had delayed behavioral recovery. Pair housing led to increased expression of BDNF and myelin protein expression. Therefore, the beneficial effects of pair housing may be related to BDNF and MBP expression and enhanced recovery after injury in aged animals.

scholarly journals Reversal of the Detrimental Effects of Post-Stroke Social Isolation by Pair-Housing is Mediated by Activation of BDNF-MAPK/ERK in Aged Mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Rajkumar Verma ◽  
Nia M. Harris ◽  
Brett D. Friedler ◽  
Joshua Crapser ◽  
Anita R. Patel ◽  
...  
Keyword(s):  
Social Isolation ◽  
Aged Mice ◽  
Post Stroke

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals Mice deficient in the NAAG synthetase II gene Rimkla are impaired in a novel object recognition task

2021 ◽  
Author(s):  
Ivonne Becker ◽  
Lihua Wang‐Eckhardt ◽  
Julia Lodder‐Gadaczek ◽  
Yong Wang ◽  
Agathe Grünewald ◽  
...  
Keyword(s):  
Object Recognition ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Object Recognition Task ◽  
Novel Object Recognition Task

scholarly journals Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain

2020 ◽  
Vol 22 (1) ◽  
pp. 99
Author(s):  
Aleah Holmes ◽  
Yan Xu ◽  
Juneyoung Lee ◽  
Michael E. Maniskas ◽  
Liang Zhu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dentate Gyrus ◽  
Social Isolation ◽  
Census Data ◽  
Elderly Women ◽  
Stroke Recovery ◽  
Tissue Loss ◽  
Female Mice ◽  
Post Stroke ◽  
The Brain

Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.

scholarly journals P013 The JAK-3 and TYK-2 / STAT pathways are activated in moderate to severe ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S136-S137
Author(s):  
M Loza ◽  
J M Brea ◽  
C Calviño-Suarez ◽  
I Baston-Rey ◽  
R Ferreiro-Iglesias ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Animal Models ◽  
Inflammatory Response ◽  
Western Blot ◽  
Signalling Pathways ◽  
Target Engagement ◽  
Inclusion Criteria ◽  
Phosphorylated Proteins ◽  
Single Centre Study ◽  
Stat Pathway

Abstract Background Ulcerative colitis (UC) is a chronic, progressive and disabling disease with a complex pathology of unknown aetiology influenced by genetic, environmental and microbiota factors that lead to an immunological and inflammatory response in the colon. Janus Activated Kinase (JAK) family plays a key role in modulating the adaptive and innate inflammatory response. The JAK/STAT pathway involvement in UC has been demonstrated in both animal models and human studies. Thus, overexpressed JAK-3 has been detected in the intestine of patients with UC, suggesting a key role in their pathophysiology and the inhibition of TYK-2 in animal models resulted in an improvement of the disease, which would explain its implication in the inflammatory process. We hypothesise here that there could be an activation of JAK-3 and TYK-2 signalling pathways in UC patients. Thus, we aimed to detect the activation of both signalling pathways by means of western-blot studies in UC patient samples Methods A prospective, observational single-centre study was designed. Inclusion criteria were adult patients with endoscopic active UC (more than Mayo-0) confirmed in a programmed colonoscopy. All patients signed informed consent. Samples were obtained from overstock of routine biopsies in the more severe segment affected of the large bowel. Tissues were homogenised and processed in order to obtain cell lysates by employing RIPA buffer and ultrasounds. The degree of activation of the JAK-3 and TYK-2 pathways was measured by detecting the phosphorylation of both targets as well as of STAT1, STAT3, STAT4, STAT5 and STAT6 through western blot by employing specific antibodies for total and phosphorylated proteins. Results 19 UC patients were consecutively included. Mean age was 46 years old. 53% were female, 47% were extensive colitis (E3) and 53% left-side colitis (E2). Regarding endoscopic activity, 26% had Mayo-1, 53% Mayo-2, and 21% Mayo-3. Immunoreactive bands for both phosphorylated JAK-3 and TYK-2 were detected in the biopsies from UC patients, evidencing that colonic inflammation leads to an activation of both targets. The study of STATs phosphorylation showed immunoreactive bands for phosphorylated forms of STAT1, STAT3, STAT4, STAT5 and STAT6 confirming the activation of both signalling-pathways in these patients (Figure 1). Conclusion The developed translational workflows involving basic/clinical research confirm the activation of both JAK-3 and TYK-2-dependent signalling pathways in UC patients, validating both kinases as targets for treating UC. The developed methodology allows studying the target engagement for future JAK-3/ TYK-2 inhibitors employed in clinical trials.

Abstract P757: Social Isolation After Stroke Reduces Cell Proliferation and Alters Brain MiRNA Profiles in the Aged Female Mice

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Aleah Holmes ◽  
Yan Xu ◽  
Juneyoung Lee ◽  
Liang Zhu ◽  
Venugopal Reddy Venna ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Social Isolation ◽  
Elderly Women ◽  
Epidemiological Studies ◽  
Stroke Recovery ◽  
Tissue Loss ◽  
Adhesive Tape ◽  
Female Mice ◽  
Post Stroke ◽  
Hippocampal Cell

Background: Social isolation (SI) and loneliness are risk factors for stroke. Epidemiological studies have shown that women tend to have a higher risk of stroke at later age and elderly women are more likely to be isolated. The mechanisms underlying the detrimental effects of SI have not been well studied in older females. We hypothesized that SI in aged female mice would lead to impaired post-stroke recovery and could lead to differential regulation of microRNAs (miRNAs). Methods: In this study, aged C57BL/6N female mice were subjected to a 60-minute middle cerebral artery occlusion (MCAO) and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. Infarct size, mortality and recovery was assessed using open field, the adhesive-tape removal task and the Y-maze test. MiRNAs were comprehensively analyzed by miRNAome analysis on stroke brain, and changes in hippocampal cell proliferation was assessed from perfused brain sections. Results: Importantly, SI immediately after stroke led to significantly larger tissue loss and higher mortality in aged females, it also significantly delayed motor/sensory recovery in the adhesive removal test and impaired overall locomotor activity. In addition, these mice also demonstrated worse post-stroke cognitive function. In parallel, brains of these mice showed reduced miR-297a-3p expression and increased miR-18a-3p and miR-200c-3p expression with SI compared to PH cohort and reduced hippocampal cell proliferation. Conclusion: The results from this study suggest that SI after stroke can increase mortality and significantly impair post-stroke recovery in aged female mice. These worse outcomes are in parallel to the significant changes in several miRNAs and reduced hippocampal cell proliferation.

scholarly journals Estradiol and luteinizing hormone reverse memory loss in phencyclidine model of schizophrenia: Evidence for hippocampal GABA action

2017 ◽  
Author(s):  
Alexander J. Riordan ◽  
Ari W. Schaler ◽  
Jackson B. Fried ◽  
Tracie A. Paine ◽  
Janice E. Thornton
Keyword(s):  
Object Recognition ◽  
Luteinizing Hormone ◽  
Declarative Memory ◽  
Memory Loss ◽  
Recognition Task ◽  
Female Rats ◽  
The Novel ◽  
Amnesic Effect ◽  
Brain Expression ◽  
Novel Object Recognition Task

ABSTRACTThe cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could rescue declarative memory in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP. To modulate E and LH, animals received hormone capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task. Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABAA agonist, GABAA antagonist, or GAD inhibitor before behavioral testing. We found that PCP reduced hippocampal GAD67 and abolished object recognition. Antide restored hippocampal GAD67 and rescued recognition memory in PCP-treated animals. Estradiol reversed PCP’s amnesic effect but failed to restore hippocampal GAD67. PCP did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABAA agonist restored memory in PCP-treated rats. Blocking hippocampal GAD or GABAA receptors in ovx animals reproduced memory loss similar to PCP and inhibited estradiol’s memory rescue in PCP-treated animals. In summary, decreasing LH or increasing E can reverse memory loss in a PCP model of schizophrenia. Alterations in hippocampal GABA may contribute to both PCP’s effects on declarative memory and the hormones’ ability to reverse them.

scholarly journals Inhibition of PDE4 by Roflumilast ameliorates sleep deprivation-induced cognitive dysfunction in C57BL/6J mice

2021 ◽  
Author(s):  
Abid Bhat ◽  
Muhammed Bishir ◽  
SR. Pandi-Perumal ◽  
Sulie Chang ◽  
Saravana Babu Chidambaram
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Dysfunction ◽  
Amyloid Beta ◽  
Recognition Task ◽  
Synaptic Proteins ◽  
Pde4 Inhibitor ◽  
Long Term Memory ◽  
Synapsin I ◽  
Memory Assessment ◽  
Novel Object Recognition Task

Sleep deprivation interferes with long-term memory and cognitive functions by over-activation of phosphodiesterase (PDE) enzymes. PDE4 is a non-redundant regulator of the cyclic nucleotides (cAMP), is densely expressed in the hippocampus, and is involved in learning and memory processes. In the present study, we investigated the effects of Roflumilast (ROF), a PDE4 inhibitor, on sleep deprivation induced cognitive dysfunction in a mouse model. Memory assessment was performed using a novel object recognition task and the cAMP level was estimated by ELISA. The alterations in the expressions of PDE4B, amyloid beta, CREB, BDNF, and synaptic proteins (Synapsin I, SAP 97, PSD 95) were assessed to gain insights on the possible mechanisms of action of ROF using the western blot technique. Results show that ROF reverse SD induced cognitive decline in mice. ROF down-regulated PDE4B and amyloid beta expressions. Additionally, ROF improved cAMP levels and the expressions of synapsin I, SAP 97, and PSD 95 in the hippocampal region of SD mice. Taken together, these results suggest that ROF can suppress the deleterious effects of SD-induced cognitive dysfunction via PDE4-mediated cAMP/CREB/BDNF cascade.

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