Life Sciences Commons^™

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

The Effect Of Infection Risk On Female Blood Transcriptomics, Brenna M. G. Gormally, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance …

Maternal Responses In The Face Of Infection Risk, Patricia C. Lopes, Brenna M. G. Gormally, Aubrey Emmi, Delilah Schuerman, Chathuni Liyanage, Ursula K. Beattie, L. Michael Romero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When animals are sick, their physiology and behavior change in ways that can impact their offspring. Research is emerging showing that infection risk alone can also modify the physiology and behavior of healthy animals. If physiological responses to environments with high infection risk take place during reproduction, it is possible that they lead to maternal effects. Understanding whether and how high infection risk triggers maternal effects is important to elucidate how the impacts of infectious agents extend beyond infected individuals and how, in this way, they are even stronger evolutionary forces than already considered. Here, to evaluate the effects of …

Female Presence Does Not Increase Testosterone But Still Ameliorates Sickness Behaviours In Male Japanese Quail, Brenna M. G. Gormally, Kaelyn Bridgette, Aubrey Emmi, Delilah Schuerman, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Infections can dramatically modify animal behaviour. The extent of these changes depends on an animal's environment. It has been proposed that testosterone modulates the suppression of behavioural symptoms of sickness under certain reproductive contexts. To further understand the role played by testosterone in modulating sickness behaviours under reproductive contexts, we studied a species, the Japanese quail, in which female exposure rapidly decreases circulating testosterone in males. Males received either an immune challenge (lipopolysaccharide – LPS) or a control injection and their behaviours, mass change and testosterone levels were quantified in the presence or absence of a female. Both the presence …

The Best Predictions In Experimental Biology Are Critical And Persuasive, Douglas S. Fudge, Andy J. Turko

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

A powerful way to evaluate scientific explanations (hypotheses) is to test the predictions that they make. In this way, predictions serve as an important bridge between abstract hypotheses and concrete experiments. Experimental biologists, however, generally receive little guidance on how to generate quality predictions. Here, we identify two important components of good predictions – criticality and persuasiveness – which relate to the ability of a prediction (and the experiment it implies) to disprove a hypothesis or to convince a skeptic that the hypothesis has merit. Using a detailed example, we demonstrate how striving for predictions that are both critical and …

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution …

A Native Function For Ran Translation And Cgg Repeats In Regulating Fragile X Protein Synthesis, Caitlin M. Rodriguez, Shannon E. Wright, Michael G. Kearse, Jill M. Haenfler, Brittany N. Flores, Yu Liu, Marius F. Ifrim, M. Rebecca Glineburg, Amy Krans, Paymaan Jafar-Nejad, Michael A. Sutton, Gary J. Bassell, Jack M. Parent, Frank Rigo, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5′-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In neurons, CGG RAN acts as an inhibitory upstream open reading frame to suppress basal FMRP production. Activation of mGluR5 receptors enhances FMRP synthesis. This enhancement requires both the CGG repeat and CGG RAN initiation sites. Using non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN. This ASO blockade enhanced endogenous FMRP expression in human …

Composition Of The Survival Motor Neuron (Smn) Complex In Drosophila Melanogaster, A. Gregory Matera, Amanda C. Raimer, Casey A. Schmidt, Jo A. Kelly, Gaith N. Droby, David Baillat, Sara Ten Have, Angus I. Lamond, Eric J. Wagner, Kelsey M. Gray

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila …

No Evidence For Kin Protection In The Expression Of Sickness Behaviors In House Mice, Patricia C. Lopes, Per Block, Alice Pontiggia, Anna K. Lindholm, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When infected, animals change their behaviors in several ways, including by decreasing their activity, their food and water intake, and their interest in social interactions. These behavioral alterations are collectively called sickness behaviors and, for several decades, the main hypotheses put forward to explain this phenomenon were that engaging in sickness behaviors facilitated the fever response and improved the likelihood of host survival. However, a new hypothesis was recently proposed suggesting that engaging in sickness behaviors may serve to protect kin. We tested this kin protection hypothesis by combining a field and a laboratory experiment in house mice. In both …

Emptying And Refilling Of Slime Glands In Atlantic (Myxine Glutinosa) And Pacific (Eptatretus Stoutii) Hagfishes, Sarah Schorno, Todd E. Gillis, Douglas S. Fudge

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Hagfishes are known for their unique defensive slime, which they use toward off gill-breathing predators. Although much is known about the slime cells (gland thread cells and gland mucous cells), little is known about how long slime gland refilling takes, or how slime composition changes with refilling or repeated stimulation of the same gland. Slime glands can be individually electrostimulated to release slime, and this technique was used to measure slime gland refilling times for Atlantic and Pacific hagfish. The amount of exudate produced, the composition of the exudate and the morphometrics of slime cells were analyzed during refilling, and …

Self-Oligomerization Regulates Stability Of Survival Motor Neuron Protein Isoforms By Sequestering An ScfSlmb Degron, Kelsey M. Gray, Kevin A. Kaifer, David Baillat, Ying Wen, Thomas R. Bonacci, Allison D. Ebert, Amanda C. Raimer, Ashlyn M. Spring, Sara Ten Have, Jacqueline J. Glascock, Kushol Gupta, Gregory D. Van Duyne, Michael J. Emanuele, Angus I. Lamond, Eric J. Wagner, Christian L. Lorson, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCF^Slmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCF^Slmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. …

Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of …