Hana Kamran | Davidson College (original) (raw)

Papers by Hana Kamran

Research paper thumbnail of Borate Transporters and SLC4 Bicarbonate Transporters Share Key Functional Properties

Membranes

Borate transporters are membrane transport proteins that regulate intracellular borate levels. In... more Borate transporters are membrane transport proteins that regulate intracellular borate levels. In plants, borate is a micronutrient essential for growth but is toxic in excess, while in yeast, borate is unnecessary for growth and borate export confers tolerance. Borate transporters share structural homology with human bicarbonate transporters in the SLC4 family despite low sequence identity and differences in transported solutes. Here, we characterize the S. cerevisiae borate transporter Bor1p and examine whether key biochemical features of SLC4 transporters extend to borate transporters. We show that borate transporters and SLC4 transporters share multiple properties, including lipid-promoted dimerization, sensitivity to stilbene disulfonate-derived inhibitors, and a requirement for an acidic residue at the solute binding site. We also identify several amino acids critical for Bor1p function and show that disease-causing mutations in human SLC4A1 will eliminate in vivo function whe...

Research paper thumbnail of Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism

Epidemiological studies suggest that alcohol use disorder (AUD) is a risk factor for Alzheimer's ... more Epidemiological studies suggest that alcohol use disorder (AUD) is a risk factor for Alzheimer's disease (AD), yet the mechanisms underlying this relationship are poorly understood. Preclinical studies consistently show that chronic, high dose ethanol exposure increases amyloid-β (Aβ) and tau pathology, hallmarks of AD, in rodent models. Conversely, other studies suggest that moderate ethanol consumption may also be protective against AD-related pathology. Thus, we used a modified two-bottle choice paradigm to identify how chronic ethanol exposure, at moderate levels, alters Aβrelated pathology, cognitive performance, and metabolism. Over the course of the experiment, APP/PS1 mice consumed more ethanol than wild-type mice. This led to changes in food and water consumption in APP/PS1 mice, where ethanolexposed APP/PS1 mice displayed a circadian shift in eating behavior. Ethanol-exposed APP/PS1 mice displayed glucose intolerance, a marker of insulin resistance, even though fasting blood glucose levels and body weights were comparable across all groups. Ethanol-exposed APP/SP1 mice exhibited deficits in nest building, a metric of self-care, as well as increased locomotor activity and central zone exploration in an open field test. Ethanol exposure also led to decreased brain mass, specifically in APP/PS1 mice, suggesting an interaction between ethanol exposure, amyloid pathology, and neurodegeneration. While there was a trend towards increased cortical Aβ deposition, there was a shift in the distribution of plaque size and numbers, with ethanol-exposed APP/PS1 mice showing a greater number of smaller plaques than H2Oexposed APP/PS1 mice. Finally, we used in vivo microdialysis to explore whether acute ethanol modulates hippocampal interstitial fluid (ISF) Aβ and ISF glucose levels in unrestrained, APP/PS1 mice. Acute intraperitoneal injection of ethanol led to a rapid rise in ISF ethanol and directly ISF Aβ (e.g. decreasing during acute exposure and increasing during acute withdrawal), and ISF glucose levels in the hippocampus. Together, these studies indicate that chronic ethanol, even at moderate doses, is sufficient to exacerbate an Alzheimer's-like phenotype in APP/PS1 mice through the direct modulation of Aβ.

Research paper thumbnail of Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism in APP/PS1 mice

Chronic ethanol exposure can increase amyloid-β (Aβ) and tau in rodent models of Alzheimer’s-dise... more Chronic ethanol exposure can increase amyloid-β (Aβ) and tau in rodent models of Alzheimer’s-disease (AD)-like pathology, yet the underlying mechanisms are poorly understood. In this study, a moderate two-bottle choice drinking paradigm was used to identify how chronic ethanol exposure alters Aβ-related pathology, metabolism, and behavior. Complementary in vivo microdialysis experiments were used to measure how acute ethanol directly modulates Aβ in the hippocampal interstitial fluid (ISF). Ethanol-exposed APPswe/PSEN1dE9 (APP/PS1) mice showed increased brain atrophy and an increased number of amyloid plaques. Further analysis revealed that ethanol exposure led to a shift in the distribution of plaque size in the cortex and hippocampus. Ethanol-exposed mice developed a greater number of smaller plaques, potentially setting the stage for increased plaque proliferation in later life. Ethanol also induced changes in N-methyl-D-aspartate and γ-aminobutyric acid type-A receptor (NMDAR an...

Research paper thumbnail of Borate Transporters and SLC4 Bicarbonate Transporters Share Key Functional Properties

Membranes

Borate transporters are membrane transport proteins that regulate intracellular borate levels. In... more Borate transporters are membrane transport proteins that regulate intracellular borate levels. In plants, borate is a micronutrient essential for growth but is toxic in excess, while in yeast, borate is unnecessary for growth and borate export confers tolerance. Borate transporters share structural homology with human bicarbonate transporters in the SLC4 family despite low sequence identity and differences in transported solutes. Here, we characterize the S. cerevisiae borate transporter Bor1p and examine whether key biochemical features of SLC4 transporters extend to borate transporters. We show that borate transporters and SLC4 transporters share multiple properties, including lipid-promoted dimerization, sensitivity to stilbene disulfonate-derived inhibitors, and a requirement for an acidic residue at the solute binding site. We also identify several amino acids critical for Bor1p function and show that disease-causing mutations in human SLC4A1 will eliminate in vivo function whe...

Research paper thumbnail of Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism

Epidemiological studies suggest that alcohol use disorder (AUD) is a risk factor for Alzheimer's ... more Epidemiological studies suggest that alcohol use disorder (AUD) is a risk factor for Alzheimer's disease (AD), yet the mechanisms underlying this relationship are poorly understood. Preclinical studies consistently show that chronic, high dose ethanol exposure increases amyloid-β (Aβ) and tau pathology, hallmarks of AD, in rodent models. Conversely, other studies suggest that moderate ethanol consumption may also be protective against AD-related pathology. Thus, we used a modified two-bottle choice paradigm to identify how chronic ethanol exposure, at moderate levels, alters Aβrelated pathology, cognitive performance, and metabolism. Over the course of the experiment, APP/PS1 mice consumed more ethanol than wild-type mice. This led to changes in food and water consumption in APP/PS1 mice, where ethanolexposed APP/PS1 mice displayed a circadian shift in eating behavior. Ethanol-exposed APP/PS1 mice displayed glucose intolerance, a marker of insulin resistance, even though fasting blood glucose levels and body weights were comparable across all groups. Ethanol-exposed APP/SP1 mice exhibited deficits in nest building, a metric of self-care, as well as increased locomotor activity and central zone exploration in an open field test. Ethanol exposure also led to decreased brain mass, specifically in APP/PS1 mice, suggesting an interaction between ethanol exposure, amyloid pathology, and neurodegeneration. While there was a trend towards increased cortical Aβ deposition, there was a shift in the distribution of plaque size and numbers, with ethanol-exposed APP/PS1 mice showing a greater number of smaller plaques than H2Oexposed APP/PS1 mice. Finally, we used in vivo microdialysis to explore whether acute ethanol modulates hippocampal interstitial fluid (ISF) Aβ and ISF glucose levels in unrestrained, APP/PS1 mice. Acute intraperitoneal injection of ethanol led to a rapid rise in ISF ethanol and directly ISF Aβ (e.g. decreasing during acute exposure and increasing during acute withdrawal), and ISF glucose levels in the hippocampus. Together, these studies indicate that chronic ethanol, even at moderate doses, is sufficient to exacerbate an Alzheimer's-like phenotype in APP/PS1 mice through the direct modulation of Aβ.

Research paper thumbnail of Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism in APP/PS1 mice

Chronic ethanol exposure can increase amyloid-β (Aβ) and tau in rodent models of Alzheimer’s-dise... more Chronic ethanol exposure can increase amyloid-β (Aβ) and tau in rodent models of Alzheimer’s-disease (AD)-like pathology, yet the underlying mechanisms are poorly understood. In this study, a moderate two-bottle choice drinking paradigm was used to identify how chronic ethanol exposure alters Aβ-related pathology, metabolism, and behavior. Complementary in vivo microdialysis experiments were used to measure how acute ethanol directly modulates Aβ in the hippocampal interstitial fluid (ISF). Ethanol-exposed APPswe/PSEN1dE9 (APP/PS1) mice showed increased brain atrophy and an increased number of amyloid plaques. Further analysis revealed that ethanol exposure led to a shift in the distribution of plaque size in the cortex and hippocampus. Ethanol-exposed mice developed a greater number of smaller plaques, potentially setting the stage for increased plaque proliferation in later life. Ethanol also induced changes in N-methyl-D-aspartate and γ-aminobutyric acid type-A receptor (NMDAR an...