Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson's Disease and Aging.

Parkinson's disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, plays a significant role in the cellular pathology of PD.

Inhibition of Calpain Attenuates Degeneration of Substantia Nigra Neurons in the Rotenone Rat Model of Parkinson's Disease.

In the central nervous system (CNS), calcium homeostasis is a critical determinant of neuronal survival. Calpain, a calcium-dependent neutral protease, is widely expressed in the brain, including substantia nigra (SN) dopaminergic (DA) neurons. Though calpain is implicated in human Parkinson's disease (PD) and corresponding animal models, the roles of specific ubiquitous calpain isoforms in PD, calpain-1 and calpain-2, remain poorly understood.

Calpain activation and progression of inflammatory cycles in Parkinson's disease.

Parkinson's disease (PD) is a progressive, neurodegenerative condition of the central nervous system (CNS) affecting 6.3 million people worldwide with no curative treatments. Current therapies aim to mitigate PD's effects and offer symptomatic relief for patients.

Cellular and molecular pathophysiology in the progression of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder etiologically linked to the loss of substantia nigra (SN) dopaminergic neurons in the mid-brain. The etiopathology of sporadic PD is still unclear; however, the interaction of extrinsic and intrinsic factors may play a critical role in the onset and progression of the disease. Studies in animal models and human post-mortem tissue have identified distinct cellular and molecular changes in the diseased brain, suggesting complex interactions between different glial cell types and various molecular pathways.

Pathophysiology, Biomarkers, and Therapeutic Modalities Associated with Skeletal Muscle Loss Following Spinal Cord Injury.

A spinal cord injury (SCI) may lead to loss of strength, sensation, locomotion and other body functions distal to the lesion site. Individuals with SCI also develop secondary conditions due to the lack of skeletal muscle activity. As SCI case numbers increase, recent studies have attempted to determine the best options to salvage affected musculature before it is lost.

Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging.

Brain-derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In this study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing Bdnf(+/-) with wildtype mice (WT) at different ages. Bdnf(+/-) and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf(+/-) mice were significantly heavier than WT mice.

Differential effects of the dopamine neurotoxin MPTP in animals with a partial deletion of the GDNF receptor, GFR alpha1, gene.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor beta (TGFbeta) superfamily, is a potent neurotrophic protein promoting the survival and maintenance of dopaminergic (DA) neurons in the substantia nigra during development and adulthood. DA neurons that project to the striatum in the nigrostriatal pathway express GDNF receptors, GFR alpha1. The purpose of this study was to determine whether these neurons are especially sensitive to neurotoxic insults.

A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Levels of GDNF deteriorate in the substantia nigra in Parkinson's disease (PD). A heterozygous mouse model was created to assess whether chronic reductions in this neurotrophic factor impact motor function and the nigrostriatal dopamine system during the aging process.

Incorporation of embryonic CA3 cell grafts into the adult hippocampus at 4-months after injury: effects of combined neurotrophic supplementation and caspase inhibition.

As receptivity of the injured hippocampus to cell grafts decreases with time after injury, strategies that improve graft integration are necessary for graft-mediated treatment of chronic neurodegenerative conditions such as temporal lobe epilepsy. We ascertained the efficacy of two distinct graft-augmentation strategies for improving the survival of embryonic day 19 hippocampal CA3 cell grafts placed into the adult hippocampus at 4-months after kainic acid induced injury. The donor cells were labeled with 5'-bromodeoxyuridine, and pre-treated and grafted with either brain-derived neurotrophic factor, neurotrophin-3 and a caspase inhibitor or fibroblast growth factor and caspase inhibitor.

Repair of the injured adult hippocampus through graft-mediated modulation of the plasticity of the dentate gyrus in a rat model of temporal lobe epilepsy.

Intracerebroventricular kainate administration in rat, a model of temporal lobe epilepsy (TLE), causes degeneration of the hippocampal CA3 pyramidal and dentate hilar neurons. This leads to a robust but aberrant sprouting of the granule cell axons (mossy fibers) into the dentate supragranular layer and the CA3 stratum oriens. Because this plasticity is linked to an increased seizure susceptibility in TLE, strategies that restrain the aberrant mossy fiber sprouting (MFS) are perceived to be important for preventing the TLE development after the hippocampal injury.

Blueberry extract enhances survival of intraocular hippocampal transplants.

Transplantation of neural tissue has been explored as a potential therapy to replace dead or dying cells in the brain, such as after brain injury or neurodegenerative disease. However, survival of transplanted tissue is poor, especially when the transplant recipient is of advanced age. Recent studies have demonstrated improvement of neuronal deficits in aged animals given a diet supplemented with blueberry extract.

Neurodegenerative alterations in the nigrostriatal system of trkB hypomorphic mice.

Brain-derived neurotrophic factor (BDNF) acts through the neurotrophin receptor TrkB and promotes survival and differentiation of dopaminergic ventral mesencephalic neurons. To further evaluate the role of TrkB in the nigrostriatal pathway, we studied neurotrophin levels, dopamine metabolism, and morphology of dopaminergic neurons of the substantia nigra (SN-DA) in young adult hypomorphic trkB mice (trkBfbz/fbz), which express only approximately 25% of wild type levels of TrkB. Tyrosine hydroxylase immunostaining revealed altered morphology of SN-DA neurons in trkBfbz/fbz when compared to wild type mice, in particular a significant enlargement of nuclear size.

Hippocampal neurotrophin levels after injury: Relationship to the age of the hippocampus at the time of injury.

Aging impairs the competence of the hippocampus for synaptic reorganization after injury. This potentially is due to the inability of the aging hippocampus to up-regulate the critical neurotrophic factors for prolonged periods after injury to levels at which they can stimulate neurite outgrowth and facilitate synaptic reorganization. We hypothesize that the concentrations of neurotrophins in the hippocampus after injury depend on the age at the time of injury.

Polymerase chain reaction in the detection of Helicobacter pylori infection.

Objective: To determine the presence of Helicobacter pylori (H. pylori) infection, in patients suffering from gastritis and peptic ulcer disease by polymerase chain reaction (PCR) and correlate the results with the histological diagnosis.

Design: Analytical, comparative study.

Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis.

This study was designed to examine stool specimens of irritable bowel syndrome (IBS) patients for Blastocystis hominis, a common intestinal parasite. One hundred fifty patients were enrolled, 95 IBS cases and 55 controls. These patients provided a medical history, and underwent physical and laboratory evaluations that included stool microscopy and culture for B.

Glial cell line-derived neurotrophic factor is essential for neuronal survival in the locus coeruleus-hippocampal noradrenergic pathway.

It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal pathway plays an important role in learning and memory processing, and that the development of this transmitter pathway is influenced by neurotrophic factors. Although some of these factors have been discovered, the regulatory mechanisms for this developmental event have not been fully elucidated. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC-NE neurons.

Polymerase chain reaction-based genotype classification among human Blastocystis hominis populations isolated from different countries.

Since the genotype of human Blastocystis hominis isolates is highly polymorphic, PCR-based genotype classification using known sequenced-tagged site (STS) primers would allow the identification or classification of different genotypes. Five populations of human B. hominis isolates obtained from Japan, Pakistan, Bangladesh, Germany, and Thailand were subjected to genotype analysis by using seven kinds of STS primers.

Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting.

A significant upregulation of neurotrophins particularly brain-derived neurotrophic factor (BDNF) is believed to be involved in the initiation of epileptogenic changes such as the aberrant axonal sprouting and synaptic reorganization in the injured hippocampus. However, it is unknown which of the neurotrophins are upregulated during the peak period of aberrant mossy fiber sprouting in the chronically injured hippocampus. We measured chronic changes in the levels of BDNF, nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the adult hippocampus using enzyme-linked immunosorbent assay (ELISA) after a unilateral intracerebroventricular administration of kainic acid (KA), a model of temporal lobe epilepsy.

Pretreatment of donor cells with FGF-2 enhances survival of fetal hippocampal CA3 cell transplants in the chronically lesioned young adult hippocampus.

The lesioned CA3 region of the young adult hippocampus is very conducive for robust survival and integration of fetal hippocampal CA3 cell grafts when transplanted at an early postlesion delay of 4 days. However, similar CA3 cell grafts placed at 45 days postlesion display significantly diminished cell survival, implying that the receptivity of the lesioned young adult host hippocampus to grafts decreases considerably with a prolonged postlesion transplantation delay. We hypothesize that decreased cell survival in grafts placed into the chronically lesioned hippocampus is due to a reduced level of host neurotrophic factors that support fetal hippocampal cells; hence, pretreatment and grafting of donor fetal CA3 cells with fibroblast growth factor-2 (FGF-2) considerably enhances graft neuronal integration into the chronically lesioned young adult hippocampus.

Fetal hippocampal CA3 cell grafts enriched with fibroblast growth factor-2 exhibit enhanced neuronal integration into the lesioned aging rat hippocampus in a kainate model of temporal lobe epilepsy.

Aging impairs the conduciveness of the lesioned hippocampus for robust survival of neurons derived from homotopic fetal cell grafts (Zaman and Shetty, Neuroscience 109:537-553, 2002), suggesting a need for graft augmentation in fetal graft-mediated therapeutic strategies for the lesioned aging hippocampus. We hypothesize that pretreatment and grafting of donor hippocampal CA3 cells with fibroblast growth factor-2 (FGF-2) considerably enhances graft neuronal integration into the lesioned CA3 region of the aging hippocampus. We employed the optical fractionator cell counting method and quantified the number of surviving cells and neurons derived from 5'-bromodoxyuridine-labeled embryonic day 19 CA3 cell grafts pre-treated and transplanted with FGF-2 into the lesioned CA3 region of the middle-aged and aged rat hippocampus at 4 days post-lesion.