Sex Differences in Fear Memory

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To learn more and watch the webinar, go to: https://insidescientific.com/webinar/sex-differences-in-fear-memory/ Memory formation and consolidation play a key role in some fear-related disorders like post-traumatic stress disorder and phobias. In order to develop more specific treatments to improve patients’ mental health, more research into the mechanisms and neural circuits underlying memory will be essential. Recent studies have shown that the Tachykinin-2 (Tac2) pathway in the central amygdala is necessary for the modulation and consolidation of fear memories. However, Dr. Raül Andero Galí has demonstrated that Tac2 blockade has an opposite effect in male and female mice: Tac2 antagonism inhibits fear memory in males but enhances it in females. In this webinar, Dr. Andero Galí presents research looking at how sex-dependent factors affect the regulation of fear memory. Key Topics Include: - Methods for the assessment of fear learning in a mouse model - Why the same drug can have different effects on memory depending on the sex and estrous cycle - How the molecular mechanisms of memory formation vary between males and females

Science

Raül Andero Galí, PhD
ICREA Research Professor – Full Professor

Disclosures
International Patent PCT/US2015/037629, Methods of
managing conditioned fear with neurokinin receptor antagonists.
ACER THERAPEUTICS

“…Fear is a generally adaptive state of
apprehension that begins rapidly and dissipates
quickly once the threat is removed.
Anxiety is elicited by less specific and less
predictable threats…”
Michael Davis
Introduction

DSM-5 (Diagnostic and Statistical
Manual of Mental Disorders 5,
2013)
Trauma
and stress-
related
disorders
E.g. PTSD
Obsessive-
compulsive
disorders
Anxiety disorders
E.g. Phobias, GAD
Fear-
related
disorders
Introduction

Cover et al. 2014 Translational Psychiatry
Introduction: Prevalence Fear-Related Disorders

Introduction: Brain Structures in Fear Memory
Flores et al. 2018 Molecular Psychiatry

Introduction: Brain Structures in Fear Memory
Beyeler A & Dabrowska J 2020 Handb Behav Neurosci

Habituation Fear acquisition Fear expression/extinction
CS: tone 6 KHz, 75 dB, 30s
US: footshock 0.3 mA, 1s.
Cued-Auditory Fear Conditioning

Andero et al. 2014 Neuron
♂
Tac2 and Fear Memory Consolidation
Habituation Fear acquisition Fear expression

Andero et al.
2014 Neuron
Osanetant
Tac2 functions
G protein-
coupled
receptor
Tac2 and Fear Memory Consolidation
Tac2 mRNA
Neurokinin B
NK3R mRNA
Duarte et al., 2006 Cell Tiss Res
CeA
Tac2(rodents)
TAC3(humans)
(Gene)
Neurokinin B (NkB)
(Peptide)
Neurokinin 3 Receptor (NK3R)
Osanetant antagonist
synthesize
binds
signalling
Memory consolidation

♂
CeA
Females?
Tac2 and Fear Memory Consolidation

Sex Differences in Fear Memory Consolidation
Habituation Fear acquisition Fear expression
Florido et al. 2021
Nature Communications

♂ ♀
Fraser et al. 2016 J Clin Endocrinol Metab
CHRONIC Nk3R
Antagonist ESN364
Hormones (HPA and HPG)

Diestrus Proestrus
Metestrus Estrus
Indirect
Florido et al. Current Protocols in
Neuroscience 2021
Hormones (HPA and HPG)
♀

♂
Hormones (HPA and HPG)
Direct
Florido et al. Current Protocols in
Neuroscience 2021
♀

Focus on
Florido et al. 2021
Nature Communications
Hormones (HPA and HPG)

Hormones (HPA and HPG)
Florido et al. 2021
Nature Communications
Estradiol

Hormones (HPA and HPG)
Florido et al. 2021
Nature Communications
Testosterone

Hormones (HPA and HPG)
Progesterone and Corticosterone NO CHANGES
Florido et al. 2021
Nature Communications

Hormones (HPA and HPG)
Florido et al. 2021
Nature Communications

Conclusion: Testosterone and Estradiol
modulation (not Progesterone or Corticosterone)
are necessary for the sex-opposite effect in
Nk3R modulation of fear memory
Hormones (HPA and HPG)

Florido et al. 2021
Nature Communications
Central Amygdala (CeA)

NO colocalization Nk3R/Androgen Receptor Florido et al. 2021 Nature Communications
Central Amygdala (CeA)

Central Amygdala (CeA)
Florido et al. 2021 Nature Communications

♂
Central Amygdala (CeA)
Andero et al. 2014 Neuron

Florido et al. 2021 Nature Communications
Central Amygdala (CeA): DREADDs

Florido et al. 2021
Nature Communications
Central Amygdala (CeA): qPCR Array and Western Blot

*
Central Amygdala (CeA): qPCR Array and Western Blot
Florido et al. 2021
Nature Communications

Maguschack et al. 2011 Nat Neuroscience
AKT
GSK
3b
mTOR
CREB
b Catenin
MEMORY
CONSOLIDATION
Nk3R
Proestrus
Phosphorilation
Phosphorilation
Florido et al. 2021 Nature Communications
Central Amygdala (CeA): Tac2 Downstream Signaling

Florido et al. 2021 Nature Communications
Central Amygdala (CeA): Cannulations

Florido et al. in preparation
CeA
BNSTpl
Amygdala Projections

www.anderolab.com @AnderoLab
Laura Pérez
PhD
Ignacio Marin
PhD
Eric Velasco
MD
Antonio Florido Patricia Molina

Thank you for participating!
CLICK HERE to learn more and
watch the webinar

Discussion 1 Week 2 Discussion Describe how genes interact with environmental factors to affect behavior Behavioral geneticists have found that specific genes can be attributed to certain psychological disorders (Durand et al., 2018). Many studies have also shown that a chaotic event in someone's childhood can influence genes (Durand et al., 2018). So, for instance, if there was the death of someone they loved very much or childhood abuse of any kind, it can alter the gene and cause it to express negatively. There is substantial scientific evidence to show that one's environment can influence an individual's behavior (Boyce et al., 2020). What Major Neurotransmitters are Associated With Mood and How are They Involved in Abnormal Behavior? Neuroscience has shown through studies that some parts of the brain and neurotransmitters play a prominent role in people's moods (Dfarhud et al., 2014). Mood is defined as a feeling that is born internally and impacts most aspects of an individual's behavior (Kawai et al., 2022). These neurotransmitters include dopamine, serotonin, norepinephrine, and endorphins (Dfarhud et al., 2014). Dopamine is a neurotransmitter made in the portion of the brain called the substantia nigra, ventral tegmental area, and hypothalamus of the brain (Juárez Olguín et al., 2016). It is believed that dopamine plays a vital role in the reward and movement part of one's brain (Juárez Olguín et al., 2016). In other words, it is released when pleasure is felt, such as sex, smell, or something that brings joy and happiness. Serotonin is also a neurotransmitter that helps regulate behavior, mood, and memory (Bamalan & Al Khalili, 2022). Some evidence shows that a reduced level of serotonin contributes to major depressive disorders, low mood, and low feelings of self-worth (Bamalan & Al Khalili, 2022). Medications used to treat low levels of serotonin often help with depression. Norepinephrine (NE) has been studied extensively over the years as it relates to suicide and other psychiatric disorders that increase the risk of suicide in patients (Chandley & Ordway, 2012). It has been found that when NE is depleted in the brain, it can result in depression (Chandley & Ordway, 2012). Caution must be used in treating bipolar 2 with NE or any antidepressant, as it can send the patient into a manic episode (Kurita, 2016). Endorphines are produced to relieve pain, reduce stress and improve mood (Cleveland Clinic, 2022). It is well known that endorphins are produced during exercise and other activities that "feel good." Therefore, they can positively impact one's outlook when they are made. This is why I believe exercise should be a part of any protocol to treat depression. What role do emotions play in psychopathology? Emotions play a role in psychopathology because emotions are implicated in psychiatric disorders associated with externalized and internalized problems. Emotions are expressed depending on ...

03.18.2016_LANDAZURI_RSE and NCSE.ppt

FrankyQ2

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psjensenmd

PAGE Running head: SCHIZOPHRENIA 1 Schizophrenia Vernessa Combs PSY350: Physiological Psychology December 10, 2019 Schizophrenia The topic selected was schizophrenia. This is a severe and chronic mental disorder affecting the way humans think, feel and behave. Although this mental disorder is not very common, it has disabling symptoms. Schizophrenia has continuously been viewed as a disorder that occurs in neurodevelopment. It is associated with a microdeletion syndrome of a chromosome. Neurons migrate to the pial surface from the brain's ventricular zone. "Migration of the neuron cell body is mediated via microtubule-based transport organized by the centrosome. First, the centrosome moves up the microtubule, followed by the nucleus and the cell body” (Pearlson, 2015). Neuronal migrations are reportedly caused by Reelin. The etiology of schizophrenia is unknown, however, several risk factors have been associated with its development. These include environmental and genetic factors. Genetic factors are, however, insufficient to account for the development of the disease. They must be accompanied by other factors for the disease to develop. "Because the concordance rate for monozygotic twins only approaches 50%, genetic makeup alone is not sufficient for the development of schizophrenia, and non-genetic or sporadic forms of the disorder must exist” (Miyamoto et al, 2013). Environmental factors that play an important role in the etiology of schizophrenia include obstetric complications such as hypoxia, preeclampsia, and premature birth. Other environmental factors include maternal viral infections and stress occurring in neurodevelopment. Stress during neurodevelopment may be caused by other factors such as microbial infections. The pathology of schizophrenia includes the transcriptional dysregulation at the cerebral cortex and chromosomal conformations. “Anatomic, neurotransmitter and immune system abnormalities have been implicated in the pathophysiology of schizophrenia” (Miyamoto et al, 2013). Differences have been observed in the brains of people with schizophrenia compared to the brains of people without the disease in neuroimaging studies. The medial temporal areas of the brain have a decreased volume while the ventricles are larger. Structural abnormalities such as volume reductions and ventricular enlargements have been associated with the disease. The dopaminergic system abnormalities are also associated with schizophrenia. The immune system is also disturbed in people with the disease. “Overactivation of the immune system (eg, from prenatal infection or postnatal stress) may result in overexpression of inflammatory cytokines and subsequent alteration of brain structure and function” (Nuckols et al, 2013). Anatomic abnormalities may also be observed in the hippocampus. In the prefrontal cortex, there has been a reported increase in neuronal density. One of the areas of the prefrontal cortex, area 9, has been found to h ...

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ExpensesU.S. CurrencyTotal 5 year Budget ProjectionFormula (see detail below)Conversion RateLocal currencyU.S. currencySourceTransportationNumberNumberLink or citationItemQtyPrice each (Local)Price each (US)Total price (US)Projected Price (US)SourceDescriptionnumbersnumber or NANumber or NAFormulasFormulasLink or citationInflation RateCPI (Five Years Ago)CPI (Today)Inflation Rate(Add rows as needed)NumberNumberFormulaLodgingItemQtyPrice each (Local)Price each (US)Total price (US)Projected PriceDescriptionnumbersnumber or NANumber or NAFormulasFormulasLink or citation(add rows as needed)Food ItemQtyPrice each (Local)Price each (US)Total price (US)Projected PriceDescriptionnumbersnumber or NANumber or NAFormulasFormulasLink or citation(add rows as needed)Supplies and MiscItemQtyPrice each (Local)Price each (US)Total price (US)Projected PriceNumbersnumbersnumber or NANumber or NAFormulasFormulasLink or citation(add rows as needed) Funding-Population ProjectionSponsorshipFundraisingLoan (remainder of trip expenses, or minimum of $10,000)Invest 30% of budget balance for 5 years$100 monthly for 5 yearsBank ABank BPrincipalFormulaPayment100PrincipalFormulaFormularnumberLink or citationrnumberLink or citationrnumberLink or citationnumberLink or citationMust be different ratesnnumbernnumbernnumbernumbertnumbertnumbertnumbernumberMust be different yearsTotal in 5 yearsFormulaTotal in 5 yearsFormulaPaymentFormulaFormulaTotal PaidFormulaFormulaTotal interestFormulaFormulaPopulation ProjectionCurrent populationNumberAnnual Growth RateNumberLink or citationProjected Population Formula In complete sentences and with complete reasoning, please answer which bank gives the better loan deal? Why? Answer: Running head: ANNOTATED BIBLIOGRAPHY 1 ANNOTATED BIBLIOGRAPHY 5 Annotated bibliography Alesix Tieku Professor Priyanthi Silva HMGT 302 (6381) February 01, 2019 Annotated bibliography Reference Alzheimer’s, A. (2015). 2015 Alzheimer's disease facts and figures. Alzheimer's & dementia: the journal of the Alzheimer's Association, 11(3), 332. The above report focuses on public health and the impacts the Alzheimer’s diseases (AD), it includes all the incidences and the prevailing mortality rates. It also covers cost incurred for caring and also the effect felt by the care givers and the society at large. This report focuses the issues encountered by the health care providers as they try to disclose the AD diagnosis to the patients as well as the care givers. Approximately 5.29 million Americans are diagnosed with AD; 200,000 have an average of below 65 years and 5.1 million are about 65 years. In the U.S. someone will develop AD after every 67 seconds. The expectations are that by 2050, AD will develop after every 33 seconds which will result to nearly a million cases per year. Ad is the sixth leading cause of death in the U.S. disclosure of the AD is usually too hard for the health specialists. Improvement of the disclosure process is suppose.

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Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...

InsideScientific

A world-wide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has triggered a pandemic and generated over 600 million reported cases around the globe. A substantial portion of patients who suffered Corona Virus Disease 2019 (COVID-19) have not recovered completely but continue to experience lingering symptoms for months to years. This novel clinical syndrome has been termed Long COVID or Post-acute Sequalae of COVID-19 (PASC). Observational studies have indicated that in about one third of cases PASC can be associated with cardiovascular (CV) autonomic dysfunction including postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension, reflex syncope and microvascular dysfunction. The presence of CV autonomic dysfunction in PASC is important to detect since although frequently overlooked, it may be effectively treated in contrast to many other Long COVID-related symptoms. This webinar highlights CV dysautonomia as a specific sequalae of acute COVID-19 and guides the audience in the diagnostic work-up of PASC patients with suspected cardiovascular complications.

Creating Better Gene-Edited Cell Lines with the FAST-HDR System

InsideScientific

Cell lines are the core of biological research. Scientists need cell lines for drug development, basic biology research, safety testing, and biologic therapeutic production. Since the 1980s, genetic manipulation has allowed researchers to tailor cell lines to the experiment or production purpose. Over time, the requirements for these cell lies have risen. In many cases, the cells require multiple genetic edits and must produce data that passes FDA. Moreover, the current funding environment often requires rapid delivery of these cells so scientists can produce data to support further budget and/or investment. This is particularly acute for knock-in cell lines. Current technologies may take months to complete a cell line, allow a limited number of edits, and often have off-target effects that are not suitable for FDA filings. ExpressCells uses its patented FAST-HDR plasmid--along with CRISPR, to address these problems. The FAST-HDR process can precisely knock-in multiple genes (while supporting other types of genetic modifications), ensure precise placement of these edits, and deliver them months faster than competing technologies. This webinar will discuss the basis of the FAST-HDR technology and illustrate several uses. The first part is a presentation by Oscar Perez-Leal, MD, the inventor of the technology. Oscar will discuss the problems he faced as a researcher and how FAST-HDR was designed to address them. He will outline the details of the technology, the history of its development, and several examples where he used FAST-HDR. The second part is a conversation with Jon Weidanz, PhD. Jon will outline the challenges he faced at AbeXXa and how he selected a FAST-HDR custom cell line for his project. He'll outline the learnings from using this cell line, some of which were unexpected, but valuable to future development. By attending this program, attendees will: - Understand the current challenges in creating custom gene-edited cell lines - Know the technology underlying the FAST-HDR gene-editing system, including its use with CRISPR - Be able to describe the advantages of the FAST-HDR system - Learn about several case studies using gene-edited cell lines

Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...

InsideScientific

Watch Dr. Sarah Greising discuss the current pathophysiologic understanding of the skeletal muscle remaining following traumatic musculoskeletal injuries. Volumetric muscle loss (VML) injuries result in the abrupt loss of skeletal muscle fibers, causing chronic functional disability in part due to limited muscle regeneration and vast co-morbidities. With a focus on clinically relevant outcome measurements for skeletal muscle function in both small and large animal models of VML injury, this webinar presents various near-term interventions for the restoration of tissue function following complex injuries. Interventions evaluated focus on regenerative rehabilitation approaches using regenerative pharmaceuticals to correct underlying muscle pathophysiology.

Designing Causal Inference Studies Using Real-World Data

InsideScientific

In this webinar, experts provide an overview of causal inference, along with step-by-step guidance to designing these studies using real-world healthcare data. Causal inference is used to answer cause and effect research questions and yield estimates of effect. Causal study design considerations and statistical methods address the effects of confounding variables and other potential biases and allow researchers to answer questions such as, “Does treatment A produce better patient outcomes compared to Treatment B?” Causal study interpretations have traditionally been restricted to randomized controlled trials; however, causal inference applied to observational healthcare data is growing in importance, driven by the need for generalizable and rapidly delivered real-world evidence to inform regulatory, payer, and patient/provider decision making. The application of causal inference methods leads to stronger and more powerful evidence. When these techniques are applied to observational data, the results generated are both from and for the real world. Presenters walk through several real-world case studies including the PCORI-funded BESTMED study and a collaborative study with a prominent pharmacy payer.

Social Media Data: Opportunities and Insights for Clinical Research

InsideScientific

Many new data are emerging in recent years - real time data is collected through digital health technologies, including apps and wearables, monitoring data, social media data, public datasets, and patient organization data, in addition to primary and secondary datasets. Real life data are highly informative and can be used to address a range of challenges throughout the product life cycle. Data from social media can generate valuable insights as patients often gather in digital communities to get answers and share their experiences. Conversations on social networks merit special consideration as they can have real world influence over treatment management decisions. Social media data can reveal the motivations that impact patient healthcare decisions and behaviors through each stage of the care pathway. These data provide both the patient and caregiver perspectives at the same time. For this reason, conversations on social networks offer an opportunity to deepen our understanding on: - The fears and hopes associated with patient treatments - Daily needs and difficulties patients are facing in managing their disease - The impact of disease on patient health related quality of life - Identification in real life of the stages of the care pathway and patient perceptions - Reactions to health policies Watch this webinar for insights on how to collect, use, analyze, and interpret social media data in different contexts. Our experts share knowledge from over fifteen years of successfully developing and adapting algorithms to treat this kind of data.

We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...

InsideScientific

To learn more visit: https://insidescientific.com/webinar/we-are-more-than-what-we-eat-dietary-interventions-depend-on-sex-and-genetic-background/ Despite evidence that sex and genetic background are key factors in the response to diet, most studies of how diet regulates metabolic health and even longevity in mice examine only a single strain and sex. Using multiple strains and both male and female mice, Dr Lamming's team has found that improvements in metabolic health and in longevity in response to reduced levels of protein or specific amino acids strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, they observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, they identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, gaining new insight into role of the energy balance hormone FG21 in the response to protein restriction.

Antibody Discovery by Single B Cell Screening on Beacon®

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Amy Sheng, PhD provides an overview of antibody screening platforms and presents applications and case studies using the Beacon® platform for antibody discovery. Single B cell screening is a powerful and efficient strategy for generating antigen-specific monoclonal antibodies. Distinguished with fluorescence-activated B cell sorting, the Beacon® platform is based on plasma cell screening, making it easier to obtain antibody genes. The Beacon® single-cell optofluidic system combines a unique optoelectro positioning (OEP) technology with novel microfluidic technology. It can be used to accurately select single cells on a chip, perform multiple single-cell assays, and export target cells based on specific results. The Beacon® optofluidic platform preserves the diversity of B cells, generating high-quality positive hits at an early stage of discovery and avoiding the loss of “good clones”. Key Topics Include: - B cell differentiation and development - Pros and cons of mainstream antibody screening platforms - Mechanisms, applications, and case studies using the Beacon® platform for antibody screening - Sino Biological’s capacity using the Beacon® platform

Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...

InsideScientific

Phil Griffiths, PhD, presents a summary of chronic cardiovascular telemetry studies and considerations for experimental design. Ensuring you collect the best and most physiologically accurate data from your chronic telemetry experiments requires careful planning and experimental design. This webinar will give an insight into the practical aspects of designing chronic animal experiments to set you on the best path for success. The benefits of chronic studies, how to select the most appropriate sample size for your study, some basic tips and tricks for data acquisition and handling, and how to ensure high animal welfare are discussed. Key Topics Include: - What are the benefits of chronic over acute studies? - How to decide the best sample sizes and the length of experiments? - Basic tips for data acquisition and handling - How to maintain high animal welfare standards

Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...

InsideScientific

In this webinar, Dr. Dennis Turner delves into dementia syndrome, the metabolic changes that occur, and the importance of proper physiological monitoring of animal models. Brain metabolism transforms with normal aging, and transient, dynamic metabolic insufficiency may underlie critical progression from aging into dementia syndrome and Alzheimer’s disease (AD). Age-related brain metabolism balances vascular-related substrate supply and transport mechanisms into extracellular space to neurons with cellular metabolic needs and utilization. Dynamic metabolic insufficiency can occur when there is intermittent supply-demand mismatch. Adequacy of neurovascular coupling to provide sufficient cerebral blood flow (CBF) to meet neuronal demand in vivo in a mouse AD model, compared to aged controls were studied. Dr. Turner’s lab analyzed the response to maximal neuronal metabolic demands, spreading depression and anoxia, using imaging, CBF measurements, and oxygen and glucose levels. These in vivo studies require human-similar anesthesia conditions, through monitoring temperature, blood pressure/pulse oximetry, and respiration, to maintain homeostasis. The lab confirmed abnormal neurovascular coupling in a mouse model of AD in response to these metabolic challenges, showing disruption much earlier in dementia than in equivalently aged individuals. Chronic metabolic treatments could influence dementia syndrome progression.

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