Sex Differences in the Neural Correlates of Specific and General Autobiographical Memory

International audienceAutobiographical memory (AM) underlies the formation and temporal continuity over time of personal identity. The few studies on sex-related differences in AM suggest that men and women adopt different cognitive or emotional strategies when retrieving AMs. However, none of the previous works has taken into account the distinction between episodic autobiographical memory (EAM), consisting in the retrieval of specific events by means of mental time travel, and semantic autobiographical memory (SAM), which stores general personal events. Thus, it remains unclear whether differences in these strategies depend on the nature of the memory content to be retrieved. In the present study we employed functional MRI to examine brain activity underlying potential sex differences in EAM and SAM retrieval focusing on the differences in strategies related to the emotional aspects of memories while controlling for basic cognitive strategies. On the behavioral level, there was no significant sex difference in memory performances or subjective feature ratings of either type of AM. Activations common to men and women during AM retrieval were observed in a typical bilateral network comprising medial and lateral temporal regions, precuneus, occipital cortex as well as prefrontal cortex. Contrast analyses revealed that there was no difference between men and women in the EAM condition. In the SAM condition, women showed an increased activity, compared to men, in the dorsal anterior cingulate cortex, inferior parietal and precentral gyrus. Overall, these findings suggest that differential neural activations reflect sex-specific strategies related to emotional aspects of AMs, particularly regarding SAM. We propose that this pattern of activation during SAM retrieval reflects the cognitive cost linked to emotion regulation strategies recruited by women compared to men. These sex-related differences have interesting implications for understanding psychiatric disorders with differential sex prevalence and in which one of key features is overgenerality in AM

Transinteractome analysis reveals distinct niche requirements for isotype‐based plasma cell subsets in the bone marrow

International audienceBone marrow (BM) long-lived plasma cells (PCs) are essential for long-term protection against infection, and their persistence within this organ relies on interactions with Cxcl12-expressing stromal cells that are still not clearly identified. Here, using single cell RNAseq and in silico transinteractome analyses, we identified Leptin receptor positive (LepR +) mesenchymal cells as the stromal cell subset most likely to interact with PCs within the BM. Moreover, we demonstrated that depending on the isotype they express, PCs may use different sets of integrins and adhesion molecules to interact with these stromal cells. Altogether, our results constitute an unprecedented characterization of PC subset stromal niches and open new avenues for the specific targeting of BM PCs based on their isotype

Age-related changes in the functional network underlying specific and general autobiographical memory retrieval: a pivotal role for the anterior cingulate cortex.

Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging

Results of the 2×2 ANOVA with condition (EAM/SAM) and group (YA/OA) as factors in the right hippocampus using region-of-interest analyses.

<p>A) Main effect of condition showed in the sagittal and the coronal plane on the left and the right respectively. B) Plots represent percentage of signal change in right hippocampus (36 –27 –6) for each condition of interest, red bars represent EAM, blue bars represent SAM, and both groups, young and old group on the left and right respectively. Statistical maps are superimposed to an MNI T1 template.</p

Contrast for each group and both conditions using cluster level correction with the false discovery rate (FDR) with p<0.05.

<p> =  Left; R  =  Right; BA  =  Brodmann Areas; ACC  =  anterior cingulate cortex; Pre-Cun  =  precuneus; sup. MPFC  =  superior medial prefrontal cortex; vMPFC  =  ventral medial prefrontal cortex; Ang. Gyr  =  angular gyrus; Hipp.  =  hippocampus; Cereb.  =  cerebellum; Inf. Par.  =  inferior parietal lobule; Mid. Temp.  =  middle temporal gyrus; MCC  =  middle cingulate cortex; Mid. Occ.  =  middle occipital gyrus; Mid. Front.  =  middle frontal gyrus; pHipp  =  parahippocampus; Mid. Front.  =  middle frontal gyrus; Sup. Front.  =  superior frontal gyrus; Inf. Par.  =  inferior parietal lobule. L </p

Neuropsychological and autobiographical measures according to the group.

<p>* p<.05; ** p <.01; *** p <.001 INHIB (interference score Stroop, inhibition). TMTB-A (trail making test B-A score, shifting). R-SPAN (running span, updating). WM ( digit, visuospatial and multimodal spans, working memory). EAM and SAM (percentage of correct responses); RT (response time); EPI (Episodic score of EAM). </p

Correlations between EPI score percentage of correct AM responses and neuropsychological scores in both groups.

<p>*p<0.05, **p<0.01, ^$p<0.06. EPI (Episodic score of EAM); EAM and SAM (percentage of correct responses); INHIB (interference score Stroop, inhibition). TMTB-A (trail making test B-A score, shifting). R-SPAN (running span, updating). WM (digit, visuospatial and multimodal spans, working memory). The correlations of the top are the ones of old group, those of the bottom are the ones of young group. Asterisks denote correlations that survived FDR correction, </p

Main results for the EAM and SAM conditions in young and old groups.

<p>Statistical maps are superimposed to an MNI T1 template. Statistical threshold was set at p<0.001 (uncorrected) with an extended threshold of k = 20.</p

Correlations between the dACC activations and the EPI score percentage of correct AM responses and neuropsychological scores in both groups.

<p> EPI (Episodic score of EAM). EAM and SAM (percentage of correct responses); INHIB (interference score Stroop, inhibition). TMTB-A (trail making test B-A score, shifting). R-SPAN (running span, updating). WM (digit, visuospatial and multimodal spans, working memory). None of the correlations survived FDR correction.</p

Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia

International audienceAcute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD-Scid-IL2rγ(null)mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies