scholarly journals Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory

2017 ◽  
Vol 114 (34) ◽  
pp. 9176-9181 ◽  
Author(s):  
Erika Atucha ◽  
Vanja Vukojevic ◽  
Raquel V. Fornari ◽  
Giacomo Ronzoni ◽  
Philippe Demougin ◽  
...  

Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock–context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.

2012 ◽  
Vol 37 (7) ◽  
pp. 1545-1553 ◽  
Author(s):  
Fernanda Cenci Vuaden ◽  
Luiz Eduardo B. Savio ◽  
Angelo L. Piato ◽  
Talita C. Pereira ◽  
Mônica R. Vianna ◽  
...  

2011 ◽  
Vol 24 (4) ◽  
pp. 299-305 ◽  
Author(s):  
Christopher R. Butler ◽  
Adam Zeman

Transient epileptic amnesia (TEA) is a recently recognised syndrome of epilepsy in which the principle manifestation of seizures is recurrent episodes of isolated memory loss. In this article, we describe the clinical and cognitive profile of this emerging syndrome, and present new data that provide at most weak support for its proposed relationship to cerebrovascular disease. TEA is often associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting and remote memory impairment. We discuss the clinical and theoretical implications of these relatively novel cognitive deficits.


2015 ◽  
Vol 112 (19) ◽  
pp. E2536-E2542 ◽  
Author(s):  
Fernando Benetti ◽  
Cristiane Regina Guerino Furini ◽  
Jociane de Carvalho Myskiw ◽  
Gustavo Provensi ◽  
Maria Beatrice Passani ◽  
...  

Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation. Third, we found that exogenous application of histamine in either hippocampal CA1 or BLA of brain histamine-depleted rats, hence amnesic, restored long-term memory; however, the time frame of memory rescue was different for the two brain structures, short lived (immediately posttraining) for BLA, long lasting (up to 6 h) for the CA1. Moreover, long-term memory was formed immediately after training restoring of histamine transmission only in the BLA. These findings reveal the essential role of histaminergic neurotransmission to provide the brain with the plasticity necessary to ensure memorization of emotionally salient events, through recruitment of alternative circuits. Hence, our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1760
Author(s):  
Novella Pugliese ◽  
Marco Picardi ◽  
Roberta Della Pepa ◽  
Claudia Giordano ◽  
Francesco Muriano ◽  
...  

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.


2021 ◽  
pp. 1-20
Author(s):  
Juandré Lambertus Bernardus Saayman ◽  
Stephanus Frederik Steyn ◽  
Christiaan Beyers Brink

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.


2021 ◽  
pp. 105477382110381
Author(s):  
Kelly Haskard-Zolnierek ◽  
Courtney Wilson ◽  
Julia Pruin ◽  
Rebecca Deason ◽  
Krista Howard

Individuals with hypothyroidism suffer from symptoms including impairments to cognition (i.e., “brain fog”). Medication can help reduce symptoms of hypothyroidism; however, brain fog may hinder adherence. The aim of this study was to determine if memory impairment and cognitive failures are related to treatment nonadherence in 441 individuals with hypothyroidism. Participants with a diagnosis of hypothyroidism and currently prescribed a thyroid hormone replacement medication were placed in two groups according to adherence level and compared on validated scales assessing impairments to memory and cognition. Results indicated a significant association between treatment nonadherence and self-reported brain fog, represented by greater cognitive and memory impairments. Nonadherent individuals indicated impairments with prospective, retrospective, and short- and long-term memory; and more cognitive failures, compared to adherent individuals. Findings suggest the importance of interventions to enhance adherence for individuals with brain fog, such as encouraging the use of reminders.


BJPsych Open ◽  
2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Robert Sigström ◽  
Axel Nordenskjöld ◽  
Anders Juréus ◽  
Caitlin Clements ◽  
Erik Joas ◽  
...  

Background There have been reports of long-term subjective memory worsening after electroconvulsive therapy (ECT). Aims To study the prevalence and risk factors of long-term subjective memory worsening among patients receiving ECT in routine clinical practice. Method Patients (n = 535, of whom 277 were included in the final analysis) were recruited from eight Swedish hospitals. Participants' subjective memory impairment was assessed before ECT and a median of 73 days after ECT using the memory item from the Comprehensive Psychopathological Rating Scale. Participants also rated their pre-ECT expectations and post-ECT evaluations of the effect of ECT on memory on a 7-point scale. We used ordinal regression to identify variables associated with subjective memory worsening and negative evaluations of the effect of ECT on memory. Results Comparisons of pre- and post-ECT assessments showed that subjective memory worsened in 16.2% of participants, remained unchanged in 52.3% and improved in 31.4%. By contrast, when asked to evaluate the effect of ECT on memory after treatment 54.6% reported a negative effect. Subjective memory worsening was associated with negative expectations before ECT, younger age and shorter duration of follow-up. Conclusions Although subjective memory improved more often than it worsened when assessed before and after ECT, a majority of patients reported that ECT had negative effects on their memory when retrospectively asked how ECT had affected it. This might suggest that some patients attribute pre-existing subjective memory impairment to ECT. Clinicians should be aware that negative expectations are associated with subjective worsening of memory after ECT.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mallory Paynich Murray ◽  
Isaac Engel ◽  
Grégory Seumois ◽  
Sara Herrera-De la Mata ◽  
Sandy Lucette Rosales ◽  
...  

AbstractInvariant natural killer T cells (iNKT cells) differentiate into thymic and peripheral NKT1, NKT2 and NKT17 subsets. Here we use RNA-seq and ATAC-seq analyses and show iNKT subsets are similar, regardless of tissue location. Lung iNKT cell subsets possess the most distinct location-specific features, shared with other innate lymphocytes in the lung, possibly consistent with increased activation. Following antigenic stimulation, iNKT cells undergo chromatin and transcriptional changes delineating two populations: one similar to follicular helper T cells and the other NK or effector like. Phenotypic analysis indicates these changes are observed long-term, suggesting that iNKT cells gene programs are not fixed, but they are capable of chromatin remodeling after antigen to give rise to additional subsets.


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