Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation

The metabolic mechanisms underlying the formation of early-life episodic memories remain poorly characterized. Here, we assessed the metabolomic profile of the rat hippocampus at different developmental ages both at baseline and following episodic learning. We report that the hippocampal metabolome significantly changes over developmental ages and that learning regulates differential arrays of metabolites according to age. The infant hippocampus had the largest number of significant changes following learning, with downregulation of 54 metabolites. Of those, a large proportion was associated with the glutathione-mediated cellular defenses against oxidative stress. Further biochemical, molecular, and behavioral assessments revealed that infantile learning evokes a rapid and persistent increase in the activity of neuronal glutathione reductase, the enzyme that regenerates reduced glutathione from its oxidized form. Inhibition of glutathione reductase selectively impaired long-term memory formation in infant but not in juvenile and adult rats, confirming its age-specific role. Thus, metabolomic profiling revealed that the hippocampal glutathione-mediated antioxidant pathway is differentially required for the formation of infantile memory.

Is Acquired Disgust More Difficult to Extinguish Than Acquired Fear? an Event-Related Potential Study

This study used the classical conditioned acquisition and extinction paradigm to compare which of the two emotions, acquired disgust and acquired fear, was more difficult to extinguish, based on behavioral assessments and the event-related potential (ERP) technique. Behavioral assessments revealed that, following successful conditioned extinction, acquired disgust was more difficult to extinguish. The ERP results showed that, at the early stage of P1, the amplitude of conditioned fear was significantly smaller than that of conditioned disgust, and both were significantly different from the amplitude under neutral conditions; at the middle stage of N2, the difference between the amplitudes of conditioned disgust and conditioned fear disappeared, but they were still significantly different from the amplitudes of conditioned neutral stimuli; at the late stage of P3, the difference between conditioned disgust and conditioned neutral stimuli disappeared, but the difference between conditioned fear and neutral stimuli remained, suggesting that acquired fear was more difficult to extinguish than acquired disgust in terms of how the brain works.

Special Education Evaluation Process

The school special education evaluation process can be a time of uncertainty for many families. Some families are apprehensive and unaware of the services that can be offered to them and their children. Many are not prepared to contribute ideas or have limited knowledge of possible resources. The chapter lays out how social workers can capitalize on their understanding of systems, mental health, child development, strengths-based perspective, social justice, and equity to best serve these families and their children during this process. The chapter presents an overview of the special education process; fundamental federal, state, and local policies and procedures; eligibility requirements; functional behavioral assessments; behavior intervention plans; and measurable individualized educational program goals. It reviews the essential steps that school social workers must take to ensure a comprehensive process while collaborating within a multidisciplinary team.

Neurochemical and Behavioral Consequences of Ethanol and/or Caffeine Exposure: Effects in Zebrafish and Rodents

: Zebrafish are increasingly being utilized to model the behavioral and neurochemical effects of pharmaceuticals and, more recently, pharmaceutical interactions. Zebrafish models of stress establish that both caffeine and ethanol influence anxiety, though few studies have implemented co-administration to assess the interaction of anxiety and reward-seeking. Caffeine exposure in zebrafish is teratogenic, causing developmental abnormalities in the cardiovascular, neuromuscular, and nervous systems of embryos and larvae. Ethanol is also a teratogen and, as an anxiolytic substance, may be able to offset the anxiogenic effects of caffeine. Co-exposure to caffeine and alcohol impacts neuroanatomy and behavior in adolescent animal models, suggesting stimulant substances may moderate the impact of alcohol on neural circuit development. Here, we review the literature describing neuropharmacological and behavioral consequences of caffeine and/or alcohol exposure in the zebrafish model, focusing on neurochemistry, locomotor effects, and behavioral assessments of stress/anxiety as reported in adolescent/juvenile and adult animals. The purpose of this review is twofold: (1) describe the work in zebrafish documenting the effects of ethanol and/or caffeine exposure and (2) compare these zebrafish studies with comparable experiments in rodents. We focus on specific neurochemical pathways (dopamine, serotonin, adenosine, GABA, adenosine), anxiety-type behaviors (assessed with novel tank, thigmotaxis, shoaling), and locomotor changes resulting from both individual and co-exposure. We compare findings in zebrafish with those in rodent models, revealing similarities across species and identifying conservation of mechanisms that potentially reinforce co-addiction.

Soluble Brain Homogenates from Diverse Human and Mouse Sources Preferentially Seed Diffuse Aβ Plaque Pathology When Injected into Newborn Mouse Hosts

Background Seeding of pathology related to Alzheimer’s disease (AD) and Lewy body disease (LBD) by the injection of tissue homogenates, purified proteins, or recombinant proteins into model systems has revealed prion-like seeding of the protein aggregates that define these disorders. Most commonly these homogenates are injected into adult mice stereotaxically. Injection of brain lysates into newborn mice represents an alternative approach of delivering seeds that could be used to direct the evolution of amyloid-β (Aβ) pathology co-mixed with either tau or α-synuclein (αSyn) pathology in vulnerable mouse models. Methods Homogenates of human pre-frontal cortex were prepared and injected into the lateral ventricles of newborn (P0) mice expressing a mutant humanized amyloid precursor protein (APP), human P301L tau, human wild type αSyn, or combinations thereof. The injected brain homogenates were prepared from AD and AD/LBD cases displaying variable degrees of Aβ pathology and co-existing tau and αSyn deposits. Behavioral assessments of APP transgenic mice injected with AD brain lysates were conducted. Results We observed that the lysates from the brains of individuals with AD (Aβ+, tau+), AD/LBD (Aβ+, tau+, αSyn+), or Pathological Aging (Aβ+, tau-, αSyn-) efficiently seeded diffuse Aβ deposits, composed primarily of Aβ42 peptides, in our transgenic host animals. Moderate seeding of cerebral amyloid angiopathy (CAA) was also observed. No animal of any genotype developed discernable tau or αSyn pathology. Fear conditioning, cognitive, outcome was not significantly altered in APP transgenic animals injected with AD brain lysates compared to nontransgenic controls. Conclusions These findings demonstrate that diffuse Aβ pathology, which is a common feature of AD, AD/LBD, and PA brains, can be easily induced by injecting newborn APP mice with crude brain homogenates. Seeding of tau or αSyn comorbidities was disappointingly inefficient in the models we used, indicating additional methodological refinement will be needed to efficiently seed AD or AD/LBD mixed pathologies by injecting newborn mice.

Primitive Reflexes and Dementia in Adults With Down Syndrome

ABSTRACTObjective:To determine whether primitive reflexes serve as an indicator of dementia in adults with Down syndrome (DS), we collected neurologic examination data, cognitive and behavioral assessments, and clinical consensus diagnoses of dementia from 92 adults with DS.Methods:In a cross-sectional, observational study of a regional cohort, chi-square and Fisher’s exact tests examined individual reflexes across diagnostic group (No, Possible, or Probable Dementia). In 64 participants with all 8 reflexes assessed, the number of primitive reflexes was assessed as a predictor of diagnosis using age-controlled multinomial logistic regression and of performance on clinical assessments (Brief Praxis Test [BPT], Severe Impairment Battery [SIB], and the Dementia Questionnaire for People with Learning Disabilities [DLD] using age-adjusted linear regression.Results:Primitive palmomental, grasp, snout, and suck reflexes were more frequent in individuals with probable dementia, but all participants showed at least one primitive reflex. Multiple primitive reflexes in combination served as a better indicator of dementia, with each additional abnormal reflex tripling probability of Probable Dementia group membership controlling for age. Abnormal reflex count was not associated with direct assessment of cognition and praxis (SIB and BPT) but associated with informant ratings of cognitive and behavioral functioning (DLD).Conclusions:The presence of multiple reflexes serves as an indicator of dementia status in DS as a supplement to direct assessment of cognition and praxis. The reflex examination may serve as a tool in the multimethod evaluation for dementia in DS, as it appears unaffected by intellectual disability and language mastery.

Designing Virtual, Moderated Studies of Early Childhood Development

With increased public access to the Internet and digital tools, web-based research has gained prevalence over the past decades. However, digital adaptations for developmental research involving children have received relatively little attention. In 2020, as the COVID-19 pandemic led to reduced social contact, causing many developmental university research laboratories to close, the scientific community began to investigate online research methods that would allow continued work. Limited resources and documentation of factors that are essential for developmental research (e.g., caregiver involvement, informed assent, controlling environmental distractions at home for children) make the transition from in-person to online research especially difficult for developmental scientists. Recognizing this, we aim to contribute to the field by describing three separate moderated virtual behavioral assessments in children ranging from 4 to 13years of age that were highly successful. The three studies encompass speech production, speech perception, and reading fluency. However varied the domains we chose, the different age groups targeted by each study and different methodological approaches, the success of our virtual adaptations shared certain commonalities with regard to how to achieve informed consent, how to plan parental involvement, how to design studies that attract and hold children’s attention and valid data collection procedures. Our combined work suggests principles for future facilitation of online developmental work. Considerations derived from these studies can serve as documented points of departure that inform and encourage additional virtual adaptations in this field.

Resveratrol Attenuates Learning, Memory, and Social Interaction Impairments in Rats Exposed to Arsenic

Arsenic (As) toxicity has deleterious effects on human health causing disorder in the brain. The aim of this study was to investigate the possible neuroprotective effect of resveratrol (RSV) on arsenic-induced neurotoxicity in rats. Neurotoxicity in rats was developed by treating As 10 mg/kg/day for 21 days orally. Animals were put into seven groups: control, vehicle, As, As+RSV10, As+RSV20 mg/kg, RSV10, and RSV20 mg/kg. Behavioral assessments such as the social interaction test, novel object recognition test, elevated plus maze, open field, the Morris water maze, in addition to assessment of biomarkers such as ferric reducing ability of plasma assay, glutathione assay, and malondialdehyde assay, were used to evaluate the effects of RSV on cognitive impairment and molecular changes induced by As. The results showed that cognitive performance impaired in As rats. RSV20 mg/kg significantly could ameliorate behavioral changes like spatial learning in days 3 and 4 ( p < 0.05 ), recognition learning and memory ( p < 0.01 ), disabilities in motor coordination and stress ( p < 0.05 ), increased anxiety ( p < 0.05 ), and social interaction deficit (sociability ( p < 0.001 ) and social memory ( p < 0.05 )). RSV20 mg/kg also attenuated molecular modifications like decreased antioxidant power ( p < 0.001 ), reduced glutathione content ( p < 0.05 ), and increased malondialdehyde level ( p < 0.05 ) induced by As. In addition to oxidative stress assessments, RSV10 mg/kg could significantly increase FRAP ( p < 0.01 ) and GSH ( p < 0.05 ); however, MDA was not significantly increased. Our current behavioral findings suggest that RSV has neuroprotective effects against AS toxicity.

Better self-concept, better future choices? Behavioral and neural changes after a naturalistic self-concept training program for adolescents

A large number of adolescents experience difficulty when choosing a suitable higher education program that matches their self-views. Stimulating self-concept development could help adolescents to increase their chances of finding a suitable major. We addressed this issue by examining the effects of a naturalistic self-concept training within a gap year context on behavioral and neural correlates of self-evaluations, as well as the long-term effects for future educational decision-making. In total, 38 adolescents/young adults (ages 16-24 years) participated in a 4-wave longitudinal study, with lab visits before, during, and after the training, including behavioral assessments and fMRI. During fMRI-scanning, they rated themselves on positive and negative traits in academic, (pro)social, and physical domains, and additionally filled out questionnaires related to self-esteem and self-concept clarity. Results showed that the positivity of domain-specific self-evaluations, self-esteem, and self-concept clarity increased during the training. Second, participants with lower medial PFC activity during self-evaluation before training showed larger self-esteem increases over the year. Moreover, mPFC activity increased after training for the evaluation of positive but not negative traits. Furthermore, individual differences in the rate of change (slope) in self-concept clarity and social self-evaluations positively predicted social adjustment to college and academic performance 6 months after training. Together, these findings suggest that self-concept can be modulated in late adolescents, with an important role of the medial PFC in relation to enhanced positive self-evaluations, and self-concept clarity as a predictor of future educational outcomes.