scholarly journals Prophylactic Ketamine Treatment Promotes Resilience to Chronic Stress and Accelerates Recovery: Correlation with Changes in Synaptic Plasticity in the CA3 Subregion of the Hippocampus

2019 ◽  
Vol 20 (7) ◽  
pp. 1726 ◽  
Author(s):  
Adam Krzystyniak ◽  
Ewa Baczynska ◽  
Marta Magnowska ◽  
Svitlana Antoniuk ◽  
Matylda Roszkowska ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Recovery Period ◽  
Structural Plasticity ◽  
Brain Regions ◽  
Spine Density ◽  
Depression And Anxiety ◽  
Stress Exposure ◽  
Animal Models Of Depression ◽  
Dendritic Spine Morphology ◽  
The Brain

Ketamine is an N-methyl-d-aspartate receptor antagonist that has gained wide attention as a potent antidepressant. It has also been recently reported to have prophylactic effects in animal models of depression and anxiety. Alterations of neuroplasticity in different brain regions; such as the hippocampus; prefrontal cortex; and amygdala; are a hallmark of stress-related disorders; and such changes may endure beyond the treatment of symptoms. The present study investigated whether a prophylactic injection of ketamine has effects on structural plasticity in the brain in mice that are subjected to chronic unpredictable stress followed by an 8-day recovery period. Ketamine administration (3 mg/kg body weight) 1 h before stress exposure increased the number of resilient animals immediately after the cessation of stress exposure and positively influenced the recovery of susceptible animals to hedonic deficits. At the end of the recovery period; ketamine-treated animals exhibited significant differences in dendritic spine density and dendritic spine morphology in brain regions associated with depression compared with saline-treated animals. These results confirm previous findings of the prophylactic effects of ketamine and provide further evidence of an association between the antidepressant-like effect of ketamine and alterations of structural plasticity in the brain

Regional differences in dendritic spine density confer resilience to chronic social defeat stress

2017 ◽  
Vol 30 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Youge Qu ◽  
Chun Yang ◽  
Qian Ren ◽  
Min Ma ◽  
Chao Dong ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Regional Differences ◽  
Social Defeat ◽  
Brain Regions ◽  
Control Group ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Chronic Social Defeat Stress ◽  
The Brain ◽  
Susceptible Group

ObjectiveAlthough alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS).MethodsWe examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS.ResultsSpine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group.ConclusionsThe results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.

Pretreatment with metformin reduced dendritic spine loss following cardiac ischaemia/reperfusion injury by preventing amyloid beta aggregation, brain inflammation and mitochondrial dysfunction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.C Chattipakorn ◽  
T Leech ◽  
N Apaijai ◽  
L Higgins ◽  
K Jinawong ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Amyloid Beta ◽  
Dendritic Spine ◽  
Saline Solution ◽  
Brain Inflammation ◽  
Funding Source ◽  
Spine Density ◽  
Ischaemia Reperfusion ◽  
Dendritic Spine Density ◽  
The Brain

Abstract Background Cognitive impairment is a major complication following acute myocardial infarction (AMI). Although reperfusion therapy is a standard treatment for AMI, it leads to additional damage to the heart, known as cardiac ischaemia/reperfusion (I/R) injury. In addition to cardiac damage, brain damage was observed following cardiac I/R including brain mitochondrial dysfunction, brain inflammation, amyloid beta aggregation, resulting in dendritic spine loss. Metformin has been reported as an effective neuroprotective agent in several brain pathologies such as stroke, diabetes-related cognitive decline, and cerebral I/R injury. However, the effects of metformin on the brain pathology after cardiac I/R have not been investigated. Purpose We hypothesized that metformin attenuates brain damages and increases dendritic spine density by preventing brain mitochondrial dysfunction, brain inflammation, and amyloid beta aggregation in non-diabetic rats. Methods Male Wistar rats (n=30) were received either sham operation (n=6) or cardiac I/R operation (n=24). Cardiac I/R was done by left anterior descending coronary artery ligation for 30 min followed by a reperfusion for 120 min. In cardiac I/R group, rats were randomly divided into 4 interventions (n=6/group) as follows; 1) vehicle (a normal saline solution), 2) 100 mg/kg of metformin (Met 100), 3) 200 mg/kg of metformin (Met 200), and 4) 400 mg/kg of metformin (Met 400). Sham operated rats were received normal saline solution. Metformin or vehicle was given to the rats at 15 min prior to cardiac ischemia via intravenous injection. At the end of reperfusion, rats were sacrificed, and the brain was rapidly removed to determine brain mitochondrial function, microglial morphology, Alzheimer's related protein, and dendritic spine density. Results Cardiac I/R led to brain mitochondrial dysfunction as indicated by increasing reactive oxygen species (ROS) levels, mitochondrial membrane depolarization, and mitochondrial swelling, compared with sham. Moreover, microglial hyperactivity was observed, together with tau hyperphosphorylation and amyloid beta aggregation, compared with sham (Fig. 1). All dosages of metformin successfully activated AMPK at the similar levels, compared with vehicle group. Mitochondrial ROS and membrane potential changes were equally improved in all groups of metformin, compared with vehicle. Although mitochondrial swelling was reduced in all groups of metformin, it was markedly reduced in Met 400 group (Fig. 1). Furthermore, microglial hyperactivity, amyloid beta aggregation, and tau hyperphosphorylation were equally reduced in all groups of metformin. For dendritic spine density, metformin significantly increased dendritic spine density, and the density was highest in Met400 group, compared with other groups (Fig. 1). Conclusion Pretreatment with metformin offers neuroprotection against the brain damages following cardiac I/R injury in a dose-dependent manner. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Thailand Research Fund (SCC), and National Science and Technology Development Agency Thailand (NC)

scholarly journals Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Audrey J. Weber ◽  
Ashley B. Adamson ◽  
Kelsey M. Greathouse ◽  
Julia P. Andrade ◽  
Cameron D. Freeman ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Spine Density ◽  
Control Of Gene Expression ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
Morphometry Analysis ◽  
Apical Dendrites

AbstractRho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.

scholarly journals The immunology of stress and the impact of inflammation on the brain and behaviour

2021 ◽  
pp. 1-8
Author(s):  
Meghna Ravi ◽  
Andrew H. Miller ◽  
Vasiliki Michopoulos
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Depression And Anxiety ◽  
Stress Exposure ◽  
Acute And Chronic Stress ◽  
Chronic Stressors ◽  
Psychiatric Conditions ◽  
Chronic Activation ◽  
The Impact ◽  
The Brain

SUMMARY Exposure to acute versus chronic stressors and threats activates the immune system in adaptive and maladaptive manners respectively. Chronic activation arising from persistent stress exposure can contribute to an inflammatory response in the periphery and in the brain that has been implicated in stress-related psychopathology, including depression and anxiety. We review the immunology of acute and chronic stress exposure, integrate this discussion with the emerging literature linking heightened immune activation and inflammation to mood and anxiety disorders, and consider the translational implications of the immune system's role in these psychiatric conditions, with a brief overview of potential interventions.

Prenatal Cocaine Increases Dendritic Spine Density in Cortical and Subcortical Brain Regions of the Rat

2009 ◽  
Vol 31 (1-2) ◽  
pp. 71-75 ◽  
Author(s):  
Maya Frankfurt ◽  
Hoau-Yan Wang ◽  
Naydu Marmolejo ◽  
Kalindi Bakshi ◽  
Eitan Friedman
Keyword(s):  
Dendritic Spine ◽  
Brain Regions ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Subcortical Brain ◽  
Prenatal Cocaine

scholarly journals Sex differences in dendritic spine density and morphology in auditory and visual cortices in adolescence and adulthood

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Emily M. Parker ◽  
Nathan L. Kindja ◽  
Claire E. J. Cheetham ◽  
Robert A. Sweet
Keyword(s):  
Sex Differences ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Brain Regions ◽  
Spine Density ◽  
Female Mice ◽  
Dendritic Spine Density ◽  
Layer 4 ◽  
Visual Cortices ◽  
Mushroom Spines

AbstractDendritic spines are small protrusions on dendrites that endow neurons with the ability to receive and transform synaptic input. Dendritic spine number and morphology are altered as a consequence of synaptic plasticity and circuit refinement during adolescence. Dendritic spine density (DSD) is significantly different based on sex in subcortical brain regions associated with the generation of sex-specific behaviors. It is largely unknown if sex differences in DSD exist in auditory and visual brain regions and if there are sex-specific changes in DSD in these regions that occur during adolescent development. We analyzed dendritic spines in 4-week-old (P28) and 12-week-old (P84) male and female mice and found that DSD is lower in female mice due in part to fewer short stubby, long stubby and short mushroom spines. We found striking layer-specific patterns including a significant age by layer interaction and significantly decreased DSD in layer 4 from P28 to P84. Together these data support the possibility of developmental sex differences in DSD in visual and auditory regions and provide evidence of layer-specific refinement of DSD over adolescent brain development.

scholarly journals Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion

2017 ◽  
Vol 114 (20) ◽  
pp. E4075-E4084 ◽  
Author(s):  
Chloe U. Wallis ◽  
Rudolf N. Cardinal ◽  
Laith Alexander ◽  
Angela C. Roberts ◽  
Hannah F. Clarke
Keyword(s):  
Negative Emotion ◽  
Brain Regions ◽  
Emotional Dysregulation ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Behavioral Correlates ◽  
The Brain ◽  
Insight Into ◽  
Human Neuroimaging

Disorders of dysregulated negative emotion such as depression and anxiety also feature increased cardiovascular mortality and decreased heart-rate variability (HRV). These disorders are correlated with dysfunction within areas 25 and 32 of the ventromedial prefrontal cortex (vmPFC), but a causal relationship between dysregulation of these areas and such symptoms has not been demonstrated. Furthermore, cross-species translation is limited by inconsistent findings between rodent fear extinction and human neuroimaging studies of negative emotion. To reconcile these literatures, we applied an investigative approach to the brain–body interactions at the core of negative emotional dysregulation. We show that, in marmoset monkeys (a nonhuman primate that has far greater vmPFC homology to humans than rodents), areas 25 and 32 have causal yet opposing roles in regulating the cardiovascular and behavioral correlates of negative emotion. In novel Pavlovian fear conditioning and extinction paradigms, pharmacological inactivation of area 25 decreased the autonomic and behavioral correlates of negative emotion expectation, whereas inactivation of area 32 increased them via generalization. Area 25 inactivation also increased resting HRV. These findings are inconsistent with current theories of rodent/primate prefrontal functional similarity, and provide insight into the role of these brain regions in affective disorders. They demonstrate that area 32 hypoactivity causes behavioral generalization relevant to anxiety, and that area 25 is a causal node governing the emotional and cardiovascular symptomatology relevant to anxiety and depression.

scholarly journals Electroacupuncture prevents cocaine-induced conditioned place preference reinstatement and attenuates ΔFosB and GluR2 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ai T. M. Nguyen ◽  
Tran V. B. Quach ◽  
Peddanna Kotha ◽  
Szu-Yu Chien ◽  
Iona J. MacDonald ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Glutamate Receptor ◽  
Dendritic Spine ◽  
Critical Role ◽  
Needle Insertion ◽  
Place Preference ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Delta Fosb ◽  
Dendritic Spine Morphology

AbstractAcupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.

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