Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal <scp>CA1</scp> neurones

Frauenknecht, Katrin; Katzav, Aviva; Lavi, R.; Sabag, Avishag; Otten, Susanne; Chapman, Joab; Sommer, Clemens

doi:10.1111/nan.12180

Cited by 25 publications

(17 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is evidence in paradigms that test the effects of different molecules, like hormones or drugs of abuse, or learning and memory experiments, that altered spine density plays an important mechanistic role in the studied behaviors [52–54]. Reports in preclinical experiments demonstrate that acquired disorders of the nervous system, including autoimmune disorders, can alter neuronal structural integrity, particularly dendrite arbors [55, 56]. There is also precedent for alterations in spine density and dendritic arbors in various psychiatric and genetic disorders [50, 57, 58].…”

Section: Resultsmentioning

confidence: 99%

The brain at risk: the sepsis syndrome and lessons from preclinical experiments

2015

View full text Add to dashboard Cite

There is a growing awareness of the chronic brain injury that results from the sepsis syndrome. We review experiments in several animal models of sepsis and show in one model, cecal ligation and puncture (CLP), that permanent structural pathology matures after the initial event. Specifically, we observed after exposure to CLP significant decreased spine density on the apical tree, but not the basal tree, of dendrites in the CA1 region of the dorsal hippocampus that was accompanied by a significantly diminished arbor of the apical dendrites, by 8 weeks, but not after 2 weeks. These novel data from dendritic arborizations elaborate information about a cohort of mice that had behaved in spatial memory tasks. These results raise questions about the relationship between long-term behavioral consequences and intervention strategies.

show abstract

Section: Resultsmentioning

confidence: 99%

The brain at risk: the sepsis syndrome and lessons from preclinical experiments

2015

View full text Add to dashboard Cite

show abstract

“…It is also noteworthy that experimental and clinical work has demonstrated the association of abnormal dendritic arborization patterns, together with altered dendritic spine density, in various psychiatric and genetic disorders (63)(64)(65). Other reports have shown that acquired disorders of the nervous system, including autoimmune disorders, can alter neuronal structural integrity (66)(67)(68)(69)(70).…”

Section: Discussionmentioning

confidence: 99%

Preclinical Models of Overwhelming Sepsis Implicate the Neural System that Encodes Contextual Fear Memory

Huerta

Robbiati

Huerta

et al. 2016

Mol Med

View full text Add to dashboard Cite

Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus. Here we show that contextual fear conditioning, a form of associative memory for fear, is chronically disrupted in CLP mice when compared to SHAM-operated animals. We also find that the excitatory neurons in the basolateral nucleus of the amygdala (BLA) and the granule cells in the dentate gyrus (DG) display significantly fewer dendritic spines in the CLP group relative to the SHAM mice, although the dendritic arbors and gross morphology of the BLA and DG are comparable between the two groups. Moreover, the basal dendrites of CA1 pyramidal neurons are unaffected in the CLP mice. Taken together, our data indicate that the structural damage in the amygdalar-hippocampal network represents the neural substrate for impaired contextual fear memory in long-term sepsis survivors. Further, our data suggest that the brain injury caused by overwhelming sepsis alters the stability of the synaptic connections involved in associative fear. These results likely have implications for the emotional imbalance observed in human sepsis survivors.

show abstract

“…Since SLE patients carrying elevated titers of DNRAbs exhibited impaired spatial memory compared to HC subjects, the mouse model appears to be a valid model for NPSLE. Changes in dendritic complexity in hippocampal neurons have been reported in a model of anti-phospholipid syndrome, although the mechanism for neuronal destruction in unknown ( Frauenknecht et al, 2014 ). There are numerous brain-reactive antibodies in SLE ( Yaniv et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-d-Aspartate Receptor

et al. 2015

View full text Add to dashboard Cite

Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at a time when DNRAbs were no longer detectable in the hippocampus. These results suggest that antibody-mediated neurocognitive impairments may be highly specific, and that spatial cognition may be particularly vulnerable to DNRAb-mediated structural and functional injury to hippocampal cells that evolves after the triggering insult is no longer present.

show abstract

Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones

Abstract: Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice.

Cited by 25 publications

References 45 publications

The brain at risk: the sepsis syndrome and lessons from preclinical experiments

The brain at risk: the sepsis syndrome and lessons from preclinical experiments

Preclinical Models of Overwhelming Sepsis Implicate the Neural System that Encodes Contextual Fear Memory

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-d-Aspartate Receptor

Contact Info

Product

Resources

About