Loss of Ataxin-1 Potentiates Alzheimer's Pathogenesis by Elevating Cerebral BACE1 Transcription.

Expansion of CAG trinucleotide repeats in ATXN1 causes spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease that impairs coordination and cognition. While ATXN1 is associated with increased Alzheimer's disease (AD) risk, CAG repeat number in AD patients is not changed. Here, we investigated the consequences of ataxin-1 loss of function and discovered that knockout of Atxn1 reduced CIC-ETV4/5-mediated inhibition of Bace1 transcription, leading to increased BACE1 levels and enhanced amyloidogenic cleavage of APP, selectively in AD-vulnerable brain regions.

Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome.

Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation.

Nasal neuron PET imaging quantifies neuron generation and degeneration.

Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality.

Graphene and water-based elastomers thin-film composites by dip-moulding.

Thin-film elastomers (elastic polymers) have a number of technologically significant applications ranging from sportswear to medical devices. In this work, we demonstrate that graphene can be used to reinforce 20 micron thin elastomer films, resulting in over 50% increase in elastic modulus at a very low loading of 0.1 wt%, while also increasing the elongation to failure.

Postsynaptic PDLIM5/Enigma Homolog binds SPAR and causes dendritic spine shrinkage.

Dendritic spine morphology is thought to play important roles in synaptic development and plasticity, and morphological derangements in spines are correlated with several neurological disorders. Here, we identified an interaction between Spine-Associated RapGAP (SPAR), a postsynaptic protein that reorganizes actin cytoskeleton and drives dendritic spine head growth, and PDLIM5/Enigma Homolog (ENH), a PDZ-LIM (postsynaptic density-95/Discs large/zona occludens 1-Lin11/Isl-1/Mec3) family member. PDLIM5 has been implicated in susceptibility to bipolar disorder, major depression, and schizophrenia, but its function in neurological disease is poorly understood.

Cellular and subcellular localization of androgen receptor immunoreactivity relative to C1 adrenergic neurons in the rostral ventrolateral medulla of male and female rats.

In male and female rats, high androgen levels can increase blood pressure. The C1 area of the rostral ventrolateral medulla (RVLM), which is crucial for blood pressure regulation, contains estrogen receptors (ERs) in pre- and postsynaptic neuronal compartments and is modulated by estrogens (Wang et al. [2006] Brain Res 1094:163-178).

Extranuclear estrogen receptor beta immunoreactivity is on doublecortin-containing cells in the adult and neonatal rat dentate gyrus.

In adult female rats, estrogen receptor (ER) activation, particularly of ERbeta, promotes hippocampal neurogenesis. We previously reported that extranuclear ERbeta immunoreactivity (ir) in adult rats is on cellular profiles in or near the granule cell layer, which is the location of newly generated cells. During development, cells in or near the granule cell layer transiently express high levels of estrogen binding and nuclear ERs.

Evidence that estrogen directly and indirectly modulates C1 adrenergic bulbospinal neurons in the rostral ventrolateral medulla.

Blood pressure in women increases after menopause, and sympathetic tone in female rats decreases with estrogen injections in the rostral ventrolateral medulla (RVLM) region that contains bulbospinal C1 adrenergic neurons and is involved in blood pressure control. We investigated the anatomical and physiological basis for estrogen effects in the RVLM. Neurons with alpha- or beta-subtypes of estrogen receptor (ER) immunoreactivity (-ir) overlapped in distribution with tyrosine hydroxylase (TH)-containing C1 neurons.

Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation.

Several lines of evidence indicate that estrogen affects hippocampal synaptic plasticity through rapid nongenomic mechanisms, possibly by binding to plasma membrane estrogen receptors (ERs). We have previously shown that ERalpha immunoreactivity (ir) is in select interneuron nuclei and in several extranuclear locations, including dendritic spines and axon terminals, within the rat hippocampal formation (Milner et al., [2001] J Comp Neurol 429:355).

The acrosomal vesicle of mouse sperm is a calcium store.

Subsequent to binding to the zona pellucida, mammalian sperm undergo a regulated sequence of events that ultimately lead to acrosomal exocytosis. Like most regulated exocytotic processes, a rise in intracellular calcium is sufficient to trigger this event although the precise mechanism of how this is achieved is still unclear. Numerous studies on mouse sperm have indicated that a voltage-operated Ca2+ channel plays some immediate role following sperm binding to the zona pellucida glycoprotein ZP3.