It is known that plant-pollinator relationships are central to the proper functioning of agricultural and ecological systems. Of the many navigation pathways pollinators use, floral scent signaling for insects is the most complex yet also the most at-risk from atmospheric human activity. Oenothera pallida, a primrose, interacts with the hawkmoth pollinators Hyles lineata and Manduca sexta, via this scent pathway. Because of their reactivity with floral scent, human-released ozone and NO2 (NOx) are the main perpetrators of scent degradation. To understand the impact of scent degradation on moth responses, I recorded changes of antennal and behavioral responses of these moths to unaltered versus degraded scent, expecting a poorer response to the degraded scent. Moth antennae act as the site of odor reception, bearing sensory hairs that detect odors, allowing the moths to navigate to scent sources. I conducted electroantennographic experiments (EAG) to record the electric signal from the insect antennae in response to each scent blend, with the degraded scent representing the impact of NOx interactions. Following the EAG, I then conducted wind tunnel behavioral experiments to investigate the impact of odor degradation on behavior, and to understand the relationship between antennal and behavioral responses in these moths. I expect that the EAG experiments will have a lower antennal response to NOx degraded scents in comparison to the normal, unaltered scent blend. Likewise, the moths might have reduced behavioral responsiveness to the degraded scent, linking the chemical biology of the scent interaction to the feeding and pollination behavior. This work has broader implications regarding the importance of plant-pollinator relationships, especially when considering environmental and agricultural health as well as the issue of food security in our changing climate.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and has been established as a risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD). The progression of AD is characterized by intracellular aggregates of phosphorylated tau protein, which is mainly found in neurons and plays an important role in the stabilization of microtubules. One of the mechanisms that may contribute to tau aggregation is decreased tau clearance by the glymphatic system, a pathway that clears solutes from the brain. This fluid movement is facilitated by the astrocytic water channel aquaporin-4 (AQP4) which is primarily localized to the astrocytic endfeet that line perivascular channels surrounding the brain vasculature. Prior studies demonstrate that solute clearance along these pathways is slowed following TBI, and that there is a loss of perivascular localization of AQP4. Based on these findings we hypothesized the loss of perivascular localization of AQP4 may impair interstitial tau clearance and promote neurodegeneration. We first tested this hypothesis by examining whether loss of perivascular AQP4 following TBI promotes tau pathology in a transgenic PS19 mouse that spontaneously develops tau pathology. We then evaluated whether deletion of perivascular AQP4 in an alpha-syntrophin knock-out mouse promotes tau pathology both in the presence and absence of TBI, and when crossed with a PS19 tauopathy mouse. Alpha-syntrophin is a protein that anchors AQP4 and is important in perivascular localization; therefore, deletion of alpha-syntrophin results in loss of localization of AQP4 and impairment of clearance. We assessed levels of pathological tau using histology on the transgenic mice and crosses both with and without TBI. If validated, our findings may suggest that loss of perivascular AQP4 may increase the brain’s vulnerability to tau aggregation and neurodegeneration following TBI and provide the basis for potential treatment to prevent the development of post-traumatic neurodegeneration.

Amyloid β (Aβ) plaques are a hallmark of Alzheimer’s disease (AD), the most common form of dementia that afflicts over 5 million Americans. Soluble proteins, including Aβ, are cleared from the brain by the glymphatic system, a brain wide network of perivascular spaces that facilitates the intermixing of cerebrospinal fluid and interstitial fluid. Prior studies report that aquaporin-4 (AQP4), a water channel polarized to perivascular astrocyte endfeet, supports glymphatic clearance of soluble proteins from the brain. In the aging brain, glymphatic clearance becomes impaired and AQP4 becomes depolarized from astrocytic endfeet. Such loss of perivascular AQP4 localization is correlated with AD status and Aβ plaque burden in the human brain. In the present study, we test whether such AQP4 depolarization promotes Aβ plaque formation. AQP4 is anchored to astrocytic endfeet via the dystrophin protein complex that includes the adaptor protein α-syntrophin (α-Syn). We crossed the α-Syn knockout mouse, which lacks perivascular AQP4 localization, with the 5XFAD mouse line which spontaneously develops Aβ plaques. Our preliminary analysis suggests that loss of perivascular AQP4 localization with α-Syn knockout increases Aβ burden relative to controls. These findings demonstrate that loss of perivascular AQP4 localization, such as occurs in the human brain in the setting of AD, contributes to the development of Aβ pathology. In the future, it may be possible that targeting the localization of AQP4 may be the basis for new therapeutics that can slow or even reverse AD pathology.

Alzheimer’s Disease (AD) is a neurodegenerative disease, characterized by amyloid-ß plaque deposition in the brain, that affects more than 5 million Americans. The glymphatic system is a network of perivascular spaces that facilitates fluid movement and solute clearance from the brain, and its dysfunction in aging has been implicated in the development of AD. The water channel aquaporin-4 (AQP4), located in astrocytic endfeet bordering the perivascular spaces, supports glymphatic function. In the aging rodent and human AD brain, loss of perivascular AQP4 localization is associated with impaired glymphatic function and increased amyloid-ß deposition. Yet the molecular basis for this loss of perivascular AQP4 localization is unknown. Aquaporin-4ex (AQP4ex) is a novel translational readthrough variant of AQP4. Selective deletion of AQP4ex results in the mislocalization of AQP4 all over the astrocytic membrane, indicating that AQP4ex is a crucial element in the perivascular localization of AQP4. In this study, we quantitatively analyze the expression and localization of AQP4ex to determine whether changes in AQP4ex associate with aging, AD status, or AD pathology. Using immunofluorescent double-labeling, confocal microscopy, and custom digital image analysis techniques, we define AQP4ex expression and localization between young and aged mice, and compare these changes between wild-type animals and transgenic animals that spontaneously form amyloid-ß plaques. Using a case series of post mortem human frontal cortical tissue, we compare AQP4ex expression between healthy young adults, cognitively intact aged subjects, and aged subjects with an AD diagnosis. This is the first characterization of AQP4ex expression in the murine brain and in a human case series, and these data will contribute to the small but growing body of research on AQP4ex and its relationship with AQP4 localization, creating opportunities to identify a new novel mechanism and novel target in AD pathology.