Publications by authors named "Ryan Milstead"

A better understanding of nicotine neurobiology is needed to reduce or prevent chronic addiction, ameliorate the detrimental effects of nicotine withdrawal, and increase successful cessation of use. Nicotine binds and activates two astrocyte-expressed nicotinic acetylcholine receptors (nAChRs), α4β2 and α7. We recently found that ( or ) expression is restricted to astrocytes in mice and humans.

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Transactive response DNA binding protein 43 kilodaltons (TDP-43) is a DNA and RNA binding protein associated with severe neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), primarily affecting motor neurons in the brain and spinal cord. Partial knockdown of TDP-43 expression in a mouse model (the amiR-TDP-43 mice) leads to progressive, age-related motor dysfunction, as observed in ALS patients. Work in Caenorhabditis elegans suggests that TDP-43 dysfunction can lead to deficits in chromatin processing and double-stranded RNA (dsRNA) accumulation, potentially activating the innate immune system and promoting neuroinflammation.

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Article Synopsis
  • RCAN1 is overexpressed in Down syndrome (DS), Alzheimer's disease (AD), and normal aging, and it may play a role in memory deficits and neurodegeneration related to these conditions.
  • Abnormal diurnal patterns and circadian disruptions are common in DS, AD, and aging, but the impact of RCAN1 on these rhythms has not been previously studied.
  • The study found that proper levels of RCAN1 are essential for maintaining normal circadian rhythms and showed that both RCAN1 deficiency and overexpression can lead to altered rest-activity patterns and activity rhythm disruptions similar to those seen in DS, AD, and aging.
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Protein kinase B (PKB/AKT) is a central kinase involved in many neurobiological processes. AKT is expressed in the brain as three isoforms, AKT1, AKT2, and AKT3. Previous studies suggest isoform-specific roles in neural function, but very few studies have examined AKT isoform expression at the cellular level.

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AKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single isoform, conditional brain-specific , and double mutant mice in behaviors relevant to neuropsychiatric disorders.

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AKT is a kinase regulating numerous cellular processes in the brain, and mutations in are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood.

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