The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) enhances GABAergic activity and produces subjective effects similar to ethanol (EtOH). The effect of chronic alcohol exposure on 3α,5α-THP concentrations has been studied in mouse, rat, and monkey limbic brain areas.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by prominent loss of the nigral dopaminergic neurons and motor symptoms, such as resting tremor and bradykinesia. Evidence suggests that neuroinflammation may play a critical role in PD pathogenesis.
Alzheimer's disease (AD) is characterized by the presence of parenchymal amyloid-beta (Aβ) plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles. Currently there are no effective treatments for AD. Immunotherapeutic approaches under development are hampered by complications related to ineffectual clearance of CAA.
Parkinson's disease (PD) is a neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Parkin (which encoded by Park2), an E3 ubiquitin ligase, is the most frequently mutated gene that has casually been linked to autosomal recessive early onset familial PD.
Explosives create shockwaves that cause blast-induced neurotrauma, one of the most common types of traumatic brain injury (TBI) linked to military service. Blast-induced TBIs are often associated with reduced cognitive and behavioral functions due to a variety of factors. To study the direct effects of military explosive blasts on brain tissue, we removed systemic factors by utilizing rat hippocampal slice cultures.
Intrauterine growth restriction (IUGR) increases the incidence of adult cardiovascular disease (CVD). The sex-specific developmental mechanisms for IUGR-induced and western high fat diet (HFD) modification of CVD remain poorly understood. We hypothesized a maternal HFD in the Sprague-Dawley rat would augment IUGR-induced CVD in the offspring through decreased cardiac function and increased extracellular matrix (ECM) remodeling and stiffness in a sex-specific manner.
Diabetic nephropathy (DN) is characterized by increased macrophage infiltration, and proinflammatory “M1” macrophages contribute to development of DN. Previous studies by us and others have reported that macrophage cyclooxygenase-2 (COX-2) plays a role in polarization and maintenance of a macrophage tissue reparative “M2” phenotype. We examined the effects of macrophage COX-2 on development of DN in type I diabetes.
Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex.
Despite rapid damping, fish swimbladders have been modelled as underwater resonant bubbles. Recent data suggest that swimbladders of sound-producing fishes use a forced rather than a resonant response to produce sound. The reason for this discrepancy has not been formally addressed, and we demonstrate, for the first time, that the structure of the swimbladder wall will affect vibratory behaviour.
We tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM).
Pur-alpha is a highly conserved sequence-specific DNA and RNA binding protein with established roles in DNA replication, RNA translation, cell cycle regulation, and maintenance of neuronal differentiation. Prior studies have shown that mice lacking Pur-alpha (−/−) display decreased neurogenesis and impaired neuronal differentiation.
Serotonergic neurons of the raphe nucleus regulate sleep, mood, endocrine function, and other processes that mature during adolescence. Alcohol abuse and binge drinking are common during human adolescence. We tested the novel hypothesis that adolescent intermittent ethanol exposure would alter the serotonergic system that would persist into adulthood.
There is now compelling evidence that TNFR2 is constitutively expressed on CD4+ Foxp3+ regulatory T cells (Tregs) and TNF-TNFR2 interaction is critical for the activation, expansion and functional stability of Tregs. However, we showed that the expression of TNFR2 was also up-regulated on CD4+ Foxp3− effector T cells (Teffs) upon TCR stimulation.
It is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n = 380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or “equivalent both sides.”
The highly programmed fragmentation of chromosomes and elimination of large amounts of nuclear DNA from the presomatic cell lineages (i.e., chromatin diminution), occurs in the embryos of the freshwater zooplankton Mesocyclops edax (S. A. Forbes, 1891) (Crustacea: Copepoda).
Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation.
Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing of extracellular matrix components. Early lethality of mice null for the BMP1 gene Bmp1 or the mTLL1 gene Tll1 has impaired in vivo studies of these proteinases.
Increasing evidence suggests that traumatic brain injury (TBI) may raise the risk of developing late-onset Parkinson's disease (PD). Recently, the peroxisome proliferation-activated receptor gamma (PPARγ) agonist pioglitazone has been demonstrated to be neuroprotective in animal models of neurodegeneration.
Ischemia-reperfusion-mediated acute kidney injury can necessitate renal replacement therapy and is a major cause of morbidity and mortality. We have identified BB3, a small molecule, which when first administered at 24 hr following renal ischemia in rats, improved survival, augmented urine output and reduced the increase in serum creatinine and blood urea nitrogen.
The mammalian brain has evolved in close synchrony with the natural environment; consequently, trends toward disengagement from natural environments in today's industrialized societies may compromise adaptive neural responses and lead to psychiatric illness.