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Hauser, C.

Publications and source records attributed to Hauser, C..

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Both systemic Calcitonin Gene Related Peptide (CGRP) and a vestibular challenge promote anxiety-related behaviors and dynamic imbalance in mice

Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and vestibular migraine, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate CGRP increased anxiety indexes and time spent in the closed arms in females but not males, while OVAR increased anxiety indexes and time spent in the closed arms in both sexes. The combination of CGRP and OVAR elicited even greater anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. Rotarod performance is influenced by dowel diameter, with larger dowels presenting greater challenges on balance function. These results suggest that both CGRP and vestibular stimulation induce anxiety-like behavior and that CGRP affects dynamic balance function in mice depending on the type of challenge presented. Findings highlight the potential translation of anti-CGRP receptor signaling therapeutics for treating motion hypersensitivity and motion-induced anxiety that manifests in vestibular migraine. Significance statementAnxiety is very common in patients with dizziness and vestibular migraine (VM). Elevated CGRP levels have been linked to migraine symptoms of increased light and touch sensitivity in mice and humans and we wondered if a systemic injection of CGRP into mice would increase anxiety and imbalance; and if mice further exposed to a vestibular stimulus would have their anxiety measures sharpened. We observed a female preponderance in both CGRP and motion-induced anxiety-like behaviors, suggesting that the role of CGRP in migraines anxiety symptoms can be recapitulated in the mouse. Our findings suggest that CGRP signaling has a pertinent role in motion-induced anxiety and dynamic imbalance, and warrants the potential use of anti-CGRP therapies for the treatment of these symptoms.

neuroscience↗

Age-Related Balance Problems in Mice Are Sharpened by the Loss of Calcitonin Gene-Related Peptide (CGRP) and a Vestibular Challenge

Aging impacts the vestibular system and contributes to imbalance. In fact, in the elderly balance deficits often precede changes in cognition. However, imbalance research is limited in assessing aging mouse models that are deficient in neuromodulators like Calcitonin Gene-Related Peptide (CGRP). We studied the loss of CGRP and its effects in the aging mouse, namely its effect on both static and dynamic imbalances. In addition, postural sway and rotarod testing were performed before and after a vestibular challenge (VC) in the 129S wildtype and the CGRP (-/-) null mice. Four age groups were tested that correspond to young adulthood, late adulthood, middle age, and senescence in humans. Our results suggest wildtype mice experience a decline in rotarod ability with increased age, while the CGRP (-/-) null mice perform poorly on rotarod early in life and do not improve. Our postural sway study suggests that a vestibular challenge can lead to significantly reduced CoP ellipse areas (freezing behaviors) in older mice, and this change occurs earlier in the CGRP (-/-) null mouse. These results indicate that CGRP is an important component of static and dynamic balance; and that the loss of CGRP can contribute to balance complications that may compound with aging.

neuroscience↗

Role of Calcitonin Gene-Related Peptide (CGRP) in Auditory, Static, and Dynamic Imbalance Behaviors: Implications for Vestibular Migraine

Migraine is a severe and chronic neurological disorder that affects [~]18% of people worldwide, the majority being female (3:1). It is characterized by recurrent, debilitating headaches and heightened sensory sensitivities. People with migraine may develop vestibular migraine (VM), characterized by a heightened motion sensitivity and preponderance for spontaneous vertigo attacks and balance problems such as postural instability. Calcitonin gene-related peptide (CGRP) is implicated in migraine and is believed to act on brain meninges or in subcortical central nervous system (CNS) structures, and CGRP-based antagonists have shown efficacy for migraine treatment. CGRP also signals at efferent synapses of the cochlea and vestibular end organs, but it is unclear if exogenous CGRP can modulate inner ear function at the end organ level and cause heightened behavioral responses consistent with VM. We tested if intraperitoneally (IP) delivered CGRP to wildtype mice can modulate end organ potentials to sound [via auditory brainstem responses (ABRs)] and jerk stimuli [via vestibular sensory evoked potentials (VsEPs)]. We also assessed behavioral measures of phonophobia [acoustic startle reflex (ASR)] and static imbalance [postural sway-center of pressure (CoP)] after IP CGRP, and observed female mice exhibited heightened sensitivities to IP CGRP in all assays. Male mice showed similar auditory sensitivity and end organ effects to CGRP, but systemic CGRP did not modify male postural sway as it did in females. In conclusion, we show that intraperitoneally delivered CGRP affects ABRs and VsEPs, and elicits behaviors suggestive of auditory hypersensitivity and postural instability in mice related to the phonophobia and postural instability seen in VM patients. Significance StatementCalcitonin Gene-Related Peptide (CGRP) has been implicated in migraine, and CGRP-based therapeutics have shown efficacy in the treatment of migraine headaches. CGRP is also present in efferent synapses of the inner ear, so we questioned if increases in systemic CGRP can act directly on inner ear end organs and modify corresponding behavioral responses. In this study, we determined systemic CGRP changes cochlear and vestibular end organ potentials and produces migraine behaviors similar to phonophobia and postural control deficits. Peripheral changes in auditory and vestibular compound action potentials following systemic CGRP administration suggest CGRP can act directly on the inner ear, which provides one site of action for CGRPs involvement in hypersensitivity to sound and movement in migraine.

neuroscience↗

Barriers to Integration of Bioinformatics into Undergraduate Life Sciences Education

Bioinformatics, a discipline that combines aspects of biology, statistics, and computer science, is increasingly important for biological research. However, bioinformatics instruction is rarely integrated into life sciences curricula at the undergraduate level. To understand why, the Network for Integrating Bioinformatics into Life Sciences Education (NIBLSE, \"nibbles\") recently undertook an extensive survey of life sciences faculty in the United States. The survey responses to open-ended questions about barriers to integration were subjected to keyword analysis. The barrier most frequently reported by the ~1,260 respondents was lack of faculty training. Faculty at associates-granting institutions report the least training in bioinformatics and the least integration of bioinformatics into their teaching. Faculty from underrepresented minority groups (URMs) in STEM reported training barriers at a higher rate than others, although the number of URM respondents was small. Interestingly, the cohort of faculty with the most recently awarded PhD degrees reported the most training but were teaching bioinformatics at a lower rate than faculty who earned their degrees in previous decades. Other barriers reported included lack of student interest in bioinformatics; lack of student preparation in mathematics, statistics, and computer science; already overly full curricula; and limited access to resources, including hardware, software, and vetted teaching materials. The results of the survey, the largest to date on bioinformatics education, will guide efforts to further integrate bioinformatics instruction into undergraduate life sciences education.

scientific communication and education↗

Bioinformatics Core Competencies for Undergraduate Life Sciences Education

Bioinformatics is becoming increasingly central to research in the life sciences. However, despite its importance, bioinformatics skills and knowledge are not well integrated in undergraduate biology education. This curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing genomic research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of life sciences faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists, as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondents degree of training, time since degree earned, and/or the Carnegie classification of the respondents institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate life sciences students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.\n\nSignificance StatementBioinformatics, an interdisciplinary field that uses techniques from computer science and mathematics to store, manage, and analyze biological data, is becoming increasingly central to modern biology research. Given the widespread use of bioinformatics and its impacts on societal problem-solving (e.g., in healthcare, agriculture, and natural resources management), there is a growing need for the integration of bioinformatics competencies into undergraduate life sciences education. Here, we present a set of bioinformatics core competencies for undergraduate life scientists developed using the results of a large national survey and the expertise of our working group of bioinformaticians and educators. We also present results from the survey on the importance of bioinformatics skills and the current state of integration of bioinformatics into biology education.

bioinformatics↗