Purpose.: Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Animal models often involve techniques IOP elevation that are surgically invasive. Here the authors describe a novel and relatively simple method inducing highly consistent, modest, repeatable in rats mice. Methods.: was elevated unilaterally by injection of polystyrene microbeads into anterior chamber to occlude aqueous outflow (2.5–7 μL) mice (1 μL). The fellow eye received equivalent saline as internal...

An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the retinal ganglion cell (RGC) neurons their axons in optic nerve. Here we show that, like other neurodegenerations, injury appears mouse glaucoma. Where RGC terminate superior colliculus, reduction active follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to deficits increases with age not necessarily associated elevated ocular pressure....

Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk developing late-onset Alzheimer's Disease (LOAD) and other neurodegenerative disorders. Recent studies provided insight into multifaceted roles TREM2 in regulating extracellular β-amyloid (Aβ) pathology, myeloid cell accumulation, inflammation observed AD, yet little is known regarding role intracellular microtubule associated protein tau (MAPT; tau) pathology diseases particular. Here we...

A few studies of long-term outcomes for pediatric functional abdominal pain (FAP) have assessed acute non-abdominal at follow-up, but none has chronic pain. We followed a cohort patients with FAP (n=155) and well control group (n=45) prospectively up to 15 years. Participants ranged in age from 18 32 years follow-up telephone interview. were classified as Resolved (n=101) versus Unresolved (n=54) based on whether they reported symptoms consistent the adult Rome III criteria gastrointestinal...

Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, mechanisms leading to onset progression remain unknown. Molecular analysis various glaucoma models has revealed involvement non-neuronal cell populations, including astrocytes, Mueller glia microglia, at early stages glaucoma. High-dose irradiation was reported have significant long-term protective...

Brimonidine is a common drug for lowering ocular pressure and may directly protect retinal ganglion cells in glaucoma. The disease involves early loss of cell transport to brain targets followed by axonal somatic degeneration. We examined whether brimonidine preserves abates degeneration rats with elevated induced laser cauterization the episcleral veins.Ocular was unilaterally 90% period 8 weeks post- cauterization. During this time, (1mg/kg/day) or vehicle (phosphate-buffered saline)...

Axon degeneration can arise from metabolic stress, potentially a result of mitochondrial dysfunction or lack appropriate substrate input. In this study, we investigated whether the vulnerability observed during optic neuropathy in DBA/2J (D2) model glaucoma is due to dysfunctional mitochondria impaired delivery axons, latter based on our observation significantly decreased glucose and monocarboxylate transporters D2 nerve (ON), human ON, mice subjected acute injury. We placed both sexes...

Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein regulates mitochondrial bioenergetics, results and striatal dopamine tyrosine hydroxylase. Mitochondria isolated from mice lacking were dysfunctional as revealed by elevated reactive oxygen species (ROS) reduced capacity produce...

Axonal transport deficits have been reported as an early pathology in several neurodegenerative disorders, including glaucoma. However, the progression and mechanisms of these are poorly understood. Previous work suggests that anterograde is affected earlier to a larger degree than retrograde transport, yet this has never examined directly vivo. Using combined tract tracing methods, we time-course retinofugal projection pre-glaucomatous (3 month-old) glaucomatous (9-13 month old) DBA/2J...

Neuroinflammation—astrogliosis, microglial activation, and changes in cytokine signaling—is a prominent feature of neurodegenerative disorders. Glaucoma is group chronic conditions that make up the leading cause irreversible blindness worldwide. Neuroinflammation has been postulated to play significant role pathogenesis progression glaucomatous neurodegeneration. Though much known regarding inflammation eye glaucoma, little about activity outside retina where pathologies develop early. We...

Reduced bone mineral density (BMD) and its clinical sequelae, osteoporosis, occur at a much greater rate in patients with Alzheimer's disease (AD), often emerging early the before significant cognitive decline is seen.Reduced BMD translates to increased fracture risk, decreased quality of life, mortality for AD patients.However, mechanism responsible this observation unclear.We hypothesize that loss an additional component prodrome-changes emerge prior dementia are mediated by dysfunction...

Abstract Naked mole‐rats are fossorial rodents native to eastern Africa that spend their lives in extensive subterranean burrows where visual cues poor. Not surprisingly, they have a degenerated eye and optic nerve, suggesting poor abilities. However, little is known about central system. To investigate the organization of system, we injected neuronal tracer into eyes naked mice compare neural structures mediating vision. We found superior colliculus lateral geniculate nucleus were severely...

ABSTRACT Objectives: Nongastrointestinal (non‐GI) somatic complaints are common in children and adults with functional gastrointestinal disorders (FGIDs). The aim of the present study was to determine whether non‐GI abdominal pain (FAP) were associated FGIDs adolescence young adulthood. Patients Methods: In a prospective clinic‐based study, adolescents (ages 8–16 years) FAP (n = 188) well controls 61) completed validated measure symptoms. Participants assessed 4 15 years later (as older...

We studied the histology and morphometrics of hairs bowhead whales (Balaena mysticetus). These are hairless except for two patches more than 300 on rostral tip lower lip chin, upper lip, a bilateral row approximately ten caudal to blowhole. Histological data indicate that in all three these areas vibrissae: they show an outermost connective tissue capsule, circumferential blood sinus system surrounding hair shaft, dense innervation follicle. Morphometric were collected diameters, epidermal...

Traumatic brain injury (TBI) has acute and chronic sequelae, including an increased risk for the development of Alzheimer's disease (AD). TBI-associated neuroinflammation is characterized by activation brain-resident microglia infiltration monocytes; however, recent studies have implicated beta-amyloid as a major manipulator inflammatory response. To examine after TBI AD-like features, these examined effects in presence absence beta-amyloid. The R1.40 mouse model cerebral amyloidosis was...

PURPOSE.Autophagy is a critical process, compromised in neurodegenerative disease, by which terminally differentiated cells like neurons manage cytoskeletal and organelle turnover.How autophagy relates to associated pathologies remain unclear.We examined optic neuropathy investigating degradation, mitochondria, autophagic vesicles the DBA2/J mouse model of glaucoma exhibiting differing levels axon transport functionality.METHODS.DBA/2J DBA/2J wt-gpnmb control mice 11 14 months age were...

Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments support, including modified cytoskeletal proteins microtubule-destabilizing elements, could be initiating factors pathogenesis. We investigated the time course of changes protein levels post-translational modifications DBA/2J mouse model glaucoma. Using anterograde tract tracing retinal projection, we assessed major transported elements as a function integrity different stages pathological...

Orientation guided by mechanosensory stimuli is a fundamental behavior that has been analyzed most effectively in simple systems, but difficult to assess mammals. This study demonstrates sparsely distributed sensory ‘hairs’ on the body of naked mole-rats provide an ideal detector array for assessment touch orienting behavior. Naked are fully subterranean rodents functionally blind and lack fur. About 40 tactile hairs (resembling facial vibrissae) found each side body, they systematically...

SUMMARY Naked mole-rats are fossorial African rodents that live in large, eusocial groups. Adult subordinate female reproductively suppressed by the dominant breeding their colonies. As a result, females remain quiescent for entire lives unless they removed from suppressive presence of female. This makes tractable model studying phenotypic plasticity. We measured skeletal growth subordinate, as changed reproductive status. After housing separately home colonies, these animals experienced...