Real-world practitioner perceptions of CARTITUDE-4 results for patients with previously treated multiple myeloma.

Introduction: Initially approved for the fifth-line or later therapeutic setting, the chimeric antigen receptor (CAR) T-cell regimen ciltacabtagene autoleucel (cilta-cel) was recently approved for second-line (2L) treatment in relapsed/refractory multiple myeloma (RRMM). Oncology practitioners use clinical trials to inform treatment, but real-world impressions and impact on practice are lacking. We aimed to determine whether presenting CARTITUDE-4 clinical trial data would impact real-world preferences/perceptions around CAR T-cell therapy.

Gonadal steroid hormone receptors in the medial amygdala contribute to experience-dependent changes in stress vulnerability.

Social experience can generate neural plasticity that changes how individuals respond to stress. Winning aggressive encounters alters how animals respond to future challenges and leads to increased plasma testosterone concentrations and androgen receptor (AR) expression in the social behavior neural network. In this project, our aim was to identify neuroendocrine mechanisms that account for changes in stress-related behavior following the establishment of dominance relationships over a two-week period.

Age-Related Memory Impairment and Sex-Specific Alterations in Phosphorylation of the Rpt6 Proteasome Subunit and Polyubiquitination in the Basolateral Amygdala and Medial Prefrontal Cortex.

Aging is marked by an accumulation of damaged and modified brain proteins, and the ubiquitin-proteasome system (UPS) is important for cellular protein degradation. Recent work has established a critical role for the UPS in memory and synaptic plasticity, but the role of the UPS in age-related cognitive decline remains poorly understood. We trained young, middle-aged, and aged male and female rats using trace fear conditioning (TFC) to investigate the effects of age and sex on memory.

Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress.

The ventromedial prefrontal cortex (vmPFC) plays a critical role in stress resilience through top-down inhibition of key stress-sensitive limbic and hindbrain structures, including the dorsal raphe nucleus (DRN). In a model of experience-dependent stress resistance, socially dominant Syrian hamsters display fewer signs of anxiety following acute social defeat when compared to subordinate or control counterparts. Further, dominants activate vmPFC neurons to a greater degree during stress than do subordinates and become stress-vulnerable following pharmacological inhibition of the vmPFC.

Age-Related Memory Impairment Is Associated with Increased zif268 Protein Accumulation and Decreased Rpt6 Phosphorylation.

Aging is associated with cognitive decline, including impairments in the ability to accurately form and recall memories. Some behavioral and brain changes associated with aging are evident as early as middle age, making the understanding of associated neurobiological mechanisms essential to aid in efforts aimed at slowing cognitive decline throughout the lifespan. Here, we found that both 15-month-old and 22-month-old rats showed impaired memory recall following trace fear conditioning.

Chemogenetic activation of an infralimbic cortex to basolateral amygdala projection promotes resistance to acute social defeat stress.

Tremendous individual differences exist in stress responsivity and social defeat stress is a key approach for identifying cellular mechanisms of stress susceptibility and resilience. Syrian hamsters show reliable territorial aggression, but after social defeat they exhibit a conditioned defeat (CD) response characterized by increased submission and an absence of aggression in future social interactions. Hamsters that achieve social dominance prior to social defeat exhibit greater defeat-induced neural activity in infralimbic (IL) cortex neurons that project to the basolateral amygdala (BLA) and reduced CD response compared to subordinate hamsters.

Age-related memory deficits are associated with changes in protein degradation in brain regions critical for trace fear conditioning.

Brain aging is accompanied by an accumulation of damaged proteins, which results from deterioration of cellular quality control mechanisms and decreased protein degradation. The ubiquitin-proteasome system (UPS) is the primary proteolytic mechanism responsible for targeted degradation. Recent work has established a critical role of the UPS in memory and synaptic plasticity, but the role of the UPS in age-related cognitive decline remains poorly understood.

Social Dominance Modulates Stress-induced Neural Activity in Medial Prefrontal Cortex Projections to the Basolateral Amygdala.

Stress is a contributing factor in the etiology of several mood and anxiety disorders, and social defeat models are used to investigate the biological basis of stress-related psychopathologies. Male Syrian hamsters are highly aggressive and territorial, but after social defeat they exhibit a conditioned defeat (CD) response which is characterized by increased submissive behavior and a failure to defend their home territory against a smaller, non-aggressive intruder. Hamsters with dominant social status show increased c-Fos expression in the infralimbic (IL) cortex following social defeat and display a reduced CD response at testing compared to subordinates and controls.

Dominance relationships in Syrian hamsters modulate neuroendocrine and behavioral responses to social stress.

Stress is a well-known risk factor for psychopathology and rodent models of social defeat have strong face, etiological, construct and predictive validity for these conditions. Syrian hamsters are highly aggressive and territorial, but after an acute social defeat experience they become submissive and no longer defend their home territory, even from a smaller, non-aggressive intruder. This defeat-induced change in social behavior is called conditioned defeat (CD).

Metabolomics reveals distinct neurochemical profiles associated with stress resilience.

Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat.

Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability.

Understanding the cellular mechanisms that control resistance and vulnerability to stress is an important step toward identifying novel targets for the prevention and treatment of stress-related mental illness. In Syrian hamsters, dominant and subordinate animals exhibit different behavioral and physiological responses to social defeat stress, with dominants showing stress resistance and subordinates showing stress vulnerability. We previously found that dominant and subordinate hamsters show different levels of defeat-induced neural activity in brain regions that modulate coping with stress, although the extent to which status-dependent differences in stress vulnerability generalize to non-social stressors is unknown.

RETRACTED: BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Proteolytic cleavage of proBDNF into mature BDNF in the basolateral amygdala is necessary for defeat-induced social avoidance.

Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in the BLA/central amygdala.

Phenotypic responses to social defeat are associated with differences in cued and contextual fear discrimination.

Conflict among individuals is one of the most common forms of stressors experienced across a variety of species, including humans. Social defeat models in mice produce two phenotypic behavioral responses characterized by prolonged social avoidance (susceptibility) or continued social interaction (resistance). The resistant phenotype has been proposed as a model of resilience to chronic stress-induced depression in humans.

GABA-mediated presynaptic inhibition is required for precision of long-term memory.

Though much attention has been given to the neural structures that underlie the long-term consolidation of contextual memories, little is known about the mechanisms responsible for the maintenance of memory precision. Here, we demonstrate a rapid time-dependent decline in memory precision in GABAB(1a) receptor knockout mice. First, we show that GABAB(1a) receptors are required for the maintenance, but not encoding, of a precise fear memory.