Complex interaction of dietary fat and Alaskan bog blueberry supplementation influences manganese mediated neurotoxicity and behavioral impairments.

Dietary fat modulates neuronal health and contributes to age-related nervous system disorders. However, the complex interaction between dietary fat and supplementation and its consequences on neurotoxic pathophysiology has been sparsely explored. The indigenous Alaskan bog blueberry (BB), is known to have anti-inflammatory properties, mostly attributed to its rich polyphenolic content.

Genetic Silencing of Fatty Acid Desaturases Modulates α-Synuclein Toxicity and Neuronal Loss in Parkinson-Like Models of .

The molecular basis of Parkinson's disease (PD) is currently unknown. There is increasing evidence that fat metabolism is at the crossroad of key molecular pathways associated with the pathophysiology of PD. Fatty acid desaturases catalyze synthesis of saturated fatty acids from monounsaturated fatty acids thereby mediating several cellular mechanisms that are associated with diseases including cancer and metabolic disorders.

Development of central respiratory control in anurans: The role of neurochemicals in the emergence of air-breathing and the hypoxic response.

Physiological and environmental factors impacting respiratory homeostasis vary throughout the course of an animal's lifespan from embryo to adult and can shape respiratory development. The developmental emergence of complex neural networks for aerial breathing dates back to ancestral vertebrates, and represents the most important process for respiratory development in extant taxa ranging from fish to mammals. While substantial progress has been made towards elucidating the anatomical and physiological underpinnings of functional respiratory control networks for air-breathing, much less is known about the mechanisms establishing these networks during early neurodevelopment.

Buccal rhythmogenesis and CO sensitivity in Lithobates catesbeianus tadpole brainstems across metamorphosis.

Bullfrog tadpoles ventilate both the buccal cavity and lung. In isolated brainstems, the midbrain/pons influences CO responsiveness and timing of lung ventilatory bursting, depending on larval development. However, little is known about midbrain/pons influences on buccal burst patterns.

Caenorhabditis Sieve: A Low-tech Instrument and Methodology for Sorting Small Multicellular Organisms.

Caenorhabditis elegans (C. elegans) is a well-established model organism used across a range of basic and biomedical research. Within the nematode research community, there is a need for an affordable and effective way to maintain large, age-matched populations of C.

Sir-2.1 mediated attenuation of α-synuclein expression by Alaskan bog blueberry polyphenols in a transgenic model of Caenorhabditis elegans.

Misfolding and accumulation of cellular protein aggregates are pathological hallmarks of aging and neurodegeneration. One such protein is α-synuclein, which when misfolded, forms aggregates and disrupts normal cellular functions of the neurons causing Parkinson's disease. Nutritional interventions abundant in pharmacologically potent polyphenols have demonstrated a therapeutic role for combating protein aggregation associated with neurodegeneration.

The rostral medulla of bullfrog tadpoles contains critical lung rhythmogenic and chemosensitive regions across metamorphosis.

The development of amphibian breathing provides insight into vertebrate respiratory control mechanisms. Neural oscillators in the rostral and caudal medulla drive ventilation in amphibians, and previous reports describe ventilatory oscillators and CO sensitive regions arise during different stages of amphibian metamorphosis. However, inconsistent findings have been enigmatic, and make comparisons to potential mammalian counterparts challenging.

BUILDing BLaST: promoting rural students' biomedical research careers using a culturally responsive, one health approach.

Background And Purpose: Most postsecondary institutions in the state of Alaska (USA) have a broad mission to serve diverse students, many of whom come from schools in rural villages that are accessible only by plane, boat, or snowmobile. The major research university, the University of Alaska in Fairbanks (UAF), serves a population whereby 40% are from groups recognized as underrepresented in the biomedical workforce. The purpose of this article is to describe the Building Infrastructure Leading to Diversity (BUILD)-supported program in the state of Alaska that seeks to engage students from rural areas with a culturally relevant approach that is centered on the One Health paradigm, integrating human, animal, and environmental health.

Behavioral Phenotyping and Pathological Indicators of Parkinson's Disease in Models.

Parkinson's disease (PD) is a neurodegenerative disorder with symptoms that progressively worsen with age. Pathologically, PD is characterized by the aggregation of α-synuclein in cells of the substantia nigra in the brain and loss of dopaminergic neurons. This pathology is associated with impaired movement and reduced cognitive function.

Mechanosensory Neuron Aging: Differential Trajectories with Lifespan-Extending Alaskan Berry and Fungal Treatments in Caenorhabditis elegans.

Many nutritional interventions that increase lifespan are also proposed to postpone age-related declines in motor and cognitive function. Potential sources of anti-aging compounds are the plants and fungi that have adapted to extreme environments. We studied the effects of four commonly consumed and culturally relevant Interior Alaska berry and fungus species (bog blueberry, lowbush cranberry, crowberry, and chaga) on the decline in overall health and neuron function and changes in touch receptor neuron morphology associated with aging.

Morphological remodeling of neurons during aging is modified by compromised protein homeostasis.

Understanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin-proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin () gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis.

Insulin signaling in the aging of healthy and proteotoxically stressed mechanosensory neurons.

Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128), or lacking this proteotoxicity stressor (polyQ0), under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi).

CO2-inhibited neurons in the medullary raphé are GABAergic.

Previous studies have reported subsets of medullary raphé neurons that are either stimulated or inhibited by CO2/pH in vitro, in situ, and in vivo. We tested the hypothesis that medullary raphé CO2-inhibited neurons are GABAergic. Extracellular recordings in unanesthetized juvenile in situ rat preparations showed reversible hypercapnia-induced suppression of 19% (63/323) of medullary raphé neurons, and this suppression persisted after antagonism of NMDA, AMPA/kainate, and GABAA receptors.

Intermittent hypercapnia enhances CO₂ responsiveness and overcomes serotonergic dysfunction.

Serotonergic dysfunction compromises ventilatory chemosensitivity and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). We have shown raphé contributions to central chemosensitivity involving serotonin (5-HT)-and γ-aminobutyric acid (GABA)-mediated mechanisms. We tested the hypothesis that mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of GABA mechanisms.

Chronic nicotine and ethanol exposure both disrupt central ventilatory responses to hypoxia in bullfrog tadpoles.

The central hypoxic ventilatory response (HVR) comprises a reduction in ventilatory activity that follows a peripherally mediated ventilatory augmentation. Chronic early developmental exposure to nicotine or ethanol are both known to impair the peripherally mediated HVR, and nicotine impairs the central HVR, but the effect of ethanol on the central HVR has not been investigated. Additionally, chronic nicotine and ethanol exposure are known to impair ventilatory responses to hypercapnia in bullfrog tadpoles but HVRs have not been tested.

Chronic, but not acute, ethanol exposure impairs central hypercapnic ventilatory drive in bullfrog tadpoles.

Chronic ethanol exposure early in development is deleterious to neural development and may impair responses to ventilatory stimuli (ventilatory drive) that maintain homeostasis. Central hypercapnic ventilatory drive (CHVD) increases ventilation to ensure pH homeostasis and accommodate the metabolic production of CO(2). We tested the hypothesis that chronic ethanol exposure impairs CHVD in bullfrog tadpoles.

Neuroplasticity of the central hypercapnic ventilatory response: teratogen-induced impairment and subsequent recovery during development.

Neuroventilation is highly plastic and exposure to either of two distinct teratogens, nicotine or ethanol, during development results in a similar loss of the neuroventilatory response to hypercapnia in bullfrog tadpoles. Whether this functional deficit is permanent or transient following nicotine or ethanol exposure was unknown. Here, we tested the persistence of hypercapnic neuroventilatory response impairments in tadpoles exposed to either 30 microg/L nicotine or 0.

Cholinergic sensitivity of the developing bullfrog (Rana catesbeiana) does not explain vulnerability to chronic nicotine exposure.

Juvenile bullfrogs previously identified as highly sensitive to acute nicotine, demonstrated normal neuroventilation following 3 wk of chronic nicotine exposure. Acute bath application of 1 microM galantamine, an acetylcholinesterase inhibitor, significantly attenuated both bullfrog normocapnic neuroventilation and response to hypercapnia in a fashion similar to that of acute nicotine. This would suggest that the developmental increase in nicotine sensitivity does not enhance vulnerability to chronic exposure, and that acute nicotine acts via endogenous acetylcholine pathways to depress neuroventilation and hypercapnic drive.

Nicotine elicits a developmentally dependent depression in bullfrog neuroventilatory response to CO(2).

Nicotine exposure is associated with numerous neurodevelopmental aberrations, including impairment of the neuroventilatory response to hypercapnia in bullfrog tadpoles and mouse neonates following prolonged developmental exposure. It is unclear how acute nicotine exposure affects neuroventilation and the neuroventilatory response to hypercapnia, or how these effects might differ from those of chronic exposure. In this study the neural correlates of ventilation were recorded from in vitro brainstem preparations derived from early and late metamorphic tadpoles and juvenile bullfrogs.

Timing and duration of developmental nicotine exposure contribute to attenuation of the tadpole hypercapnic neuroventilatory response.

The ability for air-breathing vertebrates to adjust ventilation in response to increased CO(2) (hypercapnia) is fundamental to maintaining pH homeostasis. Developmental nicotine exposure has been shown to impair tadpole neuroventilatory responses to hypercapnia following 8-12 weeks of exposure. It is not clear, however, to what extent the timing of exposure during development and/or the duration over which the exposure takes place contribute to this impairment.

Developmental exposure to ethanol or nicotine inhibits the hypercapnic ventilatory response in tadpoles.

Tadpoles, Lithobates (formerly Rana) catesbeiana, were held for 8-12 weeks in pond water that was either teratogen free or contained 0.15% ethanol or 30 microg/L nicotine. The ventilatory and neuroventilatory consequences of these developmental exposures were assessed.

Catastrophic reproductive failure, terrestrial survival, and persistence of the marbled salamander.

Wide variation in reproductive success is common among amphibians that breed in seasonal ponds, but persistence of adults can buffer against these fluctuations, particularly for long-lived species. We hypothesized that the frequent episodes of catastrophic failure of the marbled salamander (Ambystoma opacum) enhance the importance of high terrestrial survival. At Rainbow Bay in South Carolina reproductive success was poor (< 1 metamorph/breeding female) in nearly half of the 22 years that the species bred.

Ontogeny of central CO2 chemoreception: chemosensitivity in the ventral medulla of developing bullfrogs.

Sites of central CO2 chemosensitivity were investigated in isolated brain stems from Rana catesbeiana tadpoles and frogs. Respiratory neurograms were made from cranial nerve (CN) 7 and spinal nerve 2. Superfusion of the brain stem with hypercapnic artificial cerebrospinal fluid elicited increased fictive lung ventilation.

Central CO2 chemoreception in developing bullfrogs: anomalous response to acetazolamide.

Central CO(2) chemoreception and the role of carbonic anhydrase were assessed in brain stems from Rana catesbeiana tadpoles and frogs. Buccal and lung rhythms were recorded from cranial nerve VII and spinal nerve II during normocapnia and hypercapnia before and after treatment with 25 microM acetazolamide. The lung response to acetazolamide mimicked the hypercapnic response in early-stage and midstage metamorphic tadpoles and frogs.

Nitric oxide mediates metabolism as well as respiratory and cardiac responses to hypoxia in the snail lymnaea stagnalis.

Lymnaea stagnalis were exposed to hypoxic and chemical challenges while ventilation, heart rate and metabolism were monitored. Hypoxia increased ventilatory behavior, but this response was eliminated by immersion in 0.75 mM nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7 NI).