scholarly journals Control of non-homeostatic feeding in sated mice using associative learning of contextual food cues

2018 ◽  
Author(s):  
Sarah A. Stern ◽  
Katherine R. Doerig ◽  
Estefania P. Azevedo ◽  
Elina Stoffel ◽  
Jeffrey M. Friedman
Keyword(s):  
Food Consumption ◽  
Food Availability ◽  
Molecular Mechanisms ◽  
Negative Reinforcement ◽  
Sensory Information ◽  
Insular Cortex ◽  
Brain Regions ◽  
Appetitive Conditioning ◽  
Functional Neuroanatomy ◽  
Intensive Training

ABSTRACTFeeding is a complex motivated behavior controlled by a distributed neural network that processes sensory information to generate adaptive behavioral responses. Accordingly, studies using appetitive Pavlovian conditioning confirm that environmental cues that are associated with food availability can induce feeding even in satiated subjects. However, in mice, appetitive conditioning generally requires intensive training and thus can impede molecular studies that often require large numbers of animals. To address this, we developed and validated a simple and rapid context-induced feeding (ctx-IF) task in which cues associated with food availability can later lead to increased food consumption in sated mice. We show that the associated increase in food consumption is driven by both positive and negative reinforcement and that spaced training is more effective than massed training. Ctx-IF can be completed in ∼1 week and provides an opportunity to study the molecular mechanisms and circuitry underlying non-homeostatic eating. We have used this paradigm to map brain regions that are activated during Ctx-IF with cFos immunohistochemistry and found that the insular cortex, and other regions, are activated following exposure to cues denoting the availability of food. Finally, we show that inhibition of the insular cortex using GABA agonists impairs performance of the task. Our findings provide a novel assay in mice for defining the functional neuroanatomy of appetitive conditioning and identify specific brain regions that are activated during the development of learned behaviors that impact food consumption.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia

2021 ◽  
pp. 1-14
Author(s):  
Debo Dong ◽  
Dezhong Yao ◽  
Yulin Wang ◽  
Seok-Jun Hong ◽  
Sarah Genon ◽  
...  
Keyword(s):  
Sensory Information ◽  
Resting State Fmri ◽  
Brain Regions ◽  
High Order ◽  
Hierarchical Organization ◽  
System Level ◽  
Integrative System ◽  
Sensorimotor Region ◽  
Cortical Hierarchy ◽  
High Level

Abstract Background Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Methods We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). Results We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal−parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). Conclusions The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory−motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.

scholarly journals Availability of ultra-processed food associated with health outcomes: a systematic review

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
T Pereira de Araújo ◽  
M Moraes ◽  
V Magalhães ◽  
C Afonso ◽  
S Rodrigues
Keyword(s):  
Risk Factors ◽  
Health Outcomes ◽  
Food Consumption ◽  
Food Availability ◽  
Overweight And Obesity ◽  
Noncommunicable Diseases ◽  
Research Association ◽  
Processed Food ◽  
Household Budget ◽  
Household Budget Surveys

Abstract Background Ultra-processed food (UPF) consumption increases worldwide, which can be harm to population's health. To establish associations between UPF and health outcomes, food consumption can be assessed individually or by using availability data, such as purchase lists or household budget surveys. The aim of this review was to search for studies on the availability of UPF related with mortality and morbidity from noncommunicable diseases or their risk factors. Methods PRISMA guideline was used. Searches were performed on PubMED, EBSCO, Scopus and Web of Science on December 2019. Search strategy included terms related with exposure (UPF) and outcomes (mortality or morbidity from noncommunicable diseases and their risk factors). Studies were selected based on the title and abstracts. Full texts were screened for eligibility and the snowballing method was used to find other relevant studies. To be based on UPF availability data and its relation with health outcomes were the inclusion criteria. Studies that assessed only food consumption at an individual level and did not present health outcome were excluded. Selection was conducted by two reviewers and a third helped when disagreement occurred. Results After duplicates removal, 560 records were analyzed. From the 11 eligible studies, 55% were conducted in more than one country. Others were performed in Brazil (27%), Guatemala (9%) and Sweden (9%). Studies were ecological (64%), cross-sectional (27%) and longitudinal (9%). All had representative samples, 45.5% were national samples, and the others were from particular population subgroups. In all studies, the only health outcomes that showed positive association with UPF availability were overweight and obesity prevalence. Conclusions Studies relating ultra-processed food availability and health outcomes are mainly focused on overweight and obesity. It is thus necessary to further explore the relationship between UPF availability and other health outcomes. Key messages It is necessary to further research association between ultra-processed food availability and other health outcomes, such as morbidity and mortality from cardiovascular diseases, diabetes or cancer. Purchase lists or household budget surveys are an important source of food availability data and can be used to relate the consumption of ultra-processed foods to health outcomes.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

scholarly journals Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode

2021 ◽  
Author(s):  
Jonas Hauser ◽  
Edoardo Pisa ◽  
Alejandro Arias Vásquez ◽  
Flavio Tomasi ◽  
Alice Traversa ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Gut Microbiota ◽  
Human Milk ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Nervous System Development ◽  
Bioactive Molecules ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Eye Opening

AbstractBreastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.

scholarly journals Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew R. Baker ◽  
Ryan Y. Wong
Keyword(s):  
Neural Plasticity ◽  
Coping Style ◽  
Molecular Mechanisms ◽  
Conditioned Fear ◽  
Coping Styles ◽  
Brain Regions ◽  
Contextual Fear Conditioning ◽  
Fear Learning ◽  
Stress Coping ◽  
Contextual Fear

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive–reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.

scholarly journals Functional Neuroanatomy of Contextual Acquisition of Concrete and Abstract Words

2009 ◽  
Vol 21 (11) ◽  
pp. 2154-2171 ◽  
Author(s):  
Anna Mestres-Missé ◽  
Thomas F. Münte ◽  
Antoni Rodriguez-Fornells
Keyword(s):  
Native Speakers ◽  
Brain Regions ◽  
Functional Neuroanatomy ◽  
Linguistic Context ◽  
Abstract Concepts ◽  
New Words ◽  
Simulation Paradigm ◽  
Abstract Words ◽  
The Brain ◽  
Concrete Words

The meaning of a novel word can be acquired by extracting it from linguistic context. Here we simulated word learning of new words associated to concrete and abstract concepts in a variant of the human simulation paradigm that provided linguistic context information in order to characterize the brain systems involved. Native speakers of Spanish read pairs of sentences in order to derive the meaning of a new word that appeared in the terminal position of the sentences. fMRI revealed that learning the meaning associated to concrete and abstract new words was qualitatively different and recruited similar brain regions as the processing of real concrete and abstract words. In particular, learning of new concrete words selectively boosted the activation of the ventral anterior fusiform gyrus, a region driven by imageability, which has previously been implicated in the processing of concrete words.

Insights into the molecular basis of host behaviour manipulation by Toxoplasma gondii infection

2017 ◽  
Vol 1 (6) ◽  
pp. 563-572 ◽  
Author(s):  
Pierre-Mehdi Hammoudi ◽  
Dominique Soldati-Favre
Keyword(s):  
Toxoplasma Gondii ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Intermediate Hosts ◽  
Toxoplasma Gondii Infection ◽  
Host Parasite ◽  
Host Behaviour ◽  
The Brain ◽  
Brain Homeostasis

Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts to enhance transmission to its feline definitive hosts, ensuring survival and dissemination. During the chronic stage of infection in rodents, a variety of neurological dysfunctions have been unravelled and correlated with the loss of cat fear, among other phenotypic impacts. However, the underlying neurological alteration(s) driving these behavioural modifications is only partially understood, which makes it difficult to draw more than a correlation between T. gondii infection and changes in brain homeostasis. Moreover, it is barely known which among the brain regions governing fear and stress responses are preferentially affected during T. gondii infection. Studies aiming at an in-depth dissection of underlying molecular mechanisms occurring at the host and parasite levels will be discussed in this review. Addressing this reminiscent topic in the light of recent technical progress and new discoveries regarding fear response, olfaction and neuromodulator mechanisms could contribute to a better understanding of this complex host–parasite interaction.

scholarly journals Mesenchymal Stem/Stromal Cell Therapy in Blood–Brain Barrier Preservation Following Ischemia: Molecular Mechanisms and Prospects

2021 ◽  
Vol 22 (18) ◽  
pp. 10045
Author(s):  
Phuong Thao Do ◽  
Chung-Che Wu ◽  
Yung-Hsiao Chiang ◽  
Chaur-Jong Hu ◽  
Kai-Yun Chen
Keyword(s):  
Stem Cells ◽  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Time Window ◽  
Brain Regions ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Pathophysiological Mechanism ◽  
Cell Based Therapy ◽  
Blood Brain

Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption of the blood–brain barrier (BBB) is a prominent pathophysiological mechanism, responsible for a series of subsequent inflammatory cascades that exacerbate the damage to brain tissue. However, the benefit of recanalization is limited in most patients because of the narrow therapeutic time window. Recently, mesenchymal stem cells (MSCs) have been assessed as excellent candidates for cell-based therapy in cerebral ischemia, including neuroinflammatory alleviation, angiogenesis and neurogenesis promotion through their paracrine actions. In addition, accumulating evidence on how MSC therapy preserves BBB integrity after stroke may open up novel therapeutic targets for treating cerebrovascular diseases. In this review, we focus on the molecular mechanisms of MSC-based therapy in the ischemia-induced prevention of BBB compromise. Currently, therapeutic effects of MSCs for stroke are primarily based on the fundamental pathogenesis of BBB breakdown, such as attenuating leukocyte infiltration, matrix metalloproteinase (MMP) regulation, antioxidant, anti-inflammation, stabilizing morphology and crosstalk between cellular components of the BBB. We also discuss prospective studies to improve the effectiveness of MSC therapy through enhanced migration into defined brain regions of stem cells. Targeted therapy is a promising new direction and is being prioritized for extensive research.

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