Curcumin reduces α-synuclein induced cytotoxicity in Parkinson's disease cell model

Background  

Overexpression and abnormal accumulation of aggregated α-synuclein (αS) have been linked to Parkinson's disease (PD) and other synucleinopathies. αS can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase αS aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction and oxidative damage in PD cell models.     

α-Synuclein overexpression increases dopamine toxicity in BE(2)-M17 cells

Background  

Oxidative stress has been proposed to be involved in the pathogenesis of Parkinson's disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine and produce various toxic molecules, i.e., free radicals and quinone species. α-Synuclein, a protein found in Lewy bodies characteristic of PD, is also thought to be involved in the pathogenesis of PD and point mutations and multiplications in the gene coding for α-synuclein have been found in familial forms of PD.     

Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice

Background  

The presynaptic protein α-synuclein is involved in a range of neurodegenerative diseases. Here we analyze potential compensatory mechanisms in α-synuclein null mutant mice. Furthermore, the findings reveal problems that may be associated with inbred mouse strains.     

Astrocyte reactivity to Fas activation is attenuated in TIMP-1 deficient mice,an <Emphasis Type="Italic">in vitro</Emphasis>study

Background  

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional secreted protein with pleiotropic actions, including the inhibition of matrix metalloproteinases (MMPs), cell death/survival and growth promoting activities. After inflammatory challenge, the levels of TIMP-1 are highly and selectively upregulated in astrocytes among glial cells, but little is know about its role in these neural cells. We investigated the influence of TIMP-1 null mutation in the reactivity of cultured astrocytes to pro-inflammatory stimuli with TNF-α and anti-Fas antibody.     

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

Background  

Granulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in α motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti-apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti-apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy.     

Tumor-infiltrating effector cells of α-galactosylceramide-induced antitumor immunity in metastatic liver tumor

Background  

α-Galactosylceramide (α-GalCer) can be presented by CD1d molecules of antigen-presenting cells, and is known to induce a potent NKT cell-dependent cytotoxic response against tumor cells. However, the main effector cells in α-GalCer-induced antitumor immunity are still controversial.     

Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers

Background  

Chronic hepatitis C virus (HCV) infection results from weak or absent T cell responses. Pegylated-interferon-alpha (IFN-α) and ribavirin, the standard of care for chronic HCV, have numerous immune effects but are not potent T cell activators. A potent immune activator such as TLR9 agonist CpG oligodeoxynucleotide (CpG) may complement current treatment approaches.     

Estrogen-Astrocyte interactions: Implications for neuroprotection

Background  

Recent work has suggested that the ovarian steroid 17β-estradiol, at physiological concentrations, may exert protective effects in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and acute ischemic stroke. While physiological concentrations of estrogen have consistently been shown to be protective in vivo, direct protection upon purified neurons is controversial, with many investigators unable to show a direct protection in highly purified primary neuronal cultures. These findings suggest that while direct protection may occur in some instances, an alternative or parallel pathway for protection may exist which could involve another cell type in the brain.     

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNa<Subscript>v</Subscript>1.2, rNa<Subscript>v</Subscript>1.4 and rNa<Subscript>v</Subscript>1.5 alpha subunits

Background  

Antillatoxin (ATX) is a structurally unique lipopeptide produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channel α-subunits at an undefined recognition site and stimulates sodium influx in neurons. However, the pharmacological properties and selectivity of ATX on the sodium channel α-subunits were not fully characterized.     

<Emphasis Type="Italic">Rgcs1</Emphasis>, a dominant QTL that affects retinal ganglion cell death after optic nerve crush in mice

Background  

Intrinsic apoptosis of neuronal somas is one aspect of neurodegenerative diseases that can be influenced by genetic background. Genes that affect this process may act as susceptibility alleles that contribute to the complex genetic nature of these diseases. Retinal ganglion cell death is a defining feature of the chronic and genetically complex neurodegenerative disease glaucoma. Previous studies using an optic nerve crush procedure in inbred mice, showed that ganglion cell resistance to crush was affected by the Mendelian-dominant inheritance of 1–2 predicted loci. To assess this further, we bred and phenotyped a large population of F2 mice derived from a resistant inbred strain (DBA/2J) and a susceptible strain (BALB/cByJ).     

Equine estrogens differentially inhibit DNA fragmentation induced by glutamate in neuronal cells by modulation of regulatory proteins involved in programmed cell death

Background  

Recent data indicate that excitotoxicity of high levels of neurotransmitter glutamate may be mediated via programmed cell death (apoptosis) and that it can be prevented in HT22 mouse hippocampal cells by various equine estrogens with Δ⁸,17β-estradiol (Δ⁸,17β-E₂) being the most potent. In order to delineate the mechanism(s), glutamate-induced cell death of HT22 cells was assessed by measuring (a) DNA fragmentation in the presence or absence of 11 equine estrogens (components of the drug CEE); (b) cell death and (c) levels of anti-apoptotic (Bcl-2) and proapoptotic (Bax) proteins in the presence or absence of two equine estrogens, Δ⁸,17β-E₂ and 17β-estradiol (17β-E₂) by LDH release assay and Western blot analysis respectively.     

Intracerebroventricular antisense knockdown of Gα<Subscript>i2</Subscript> results in ciliary stasis and ventricular dilatation in the rat

Background  

In the CNS, the heterotrimeric G protein Gα_i2 is a minor Gα subunit with restricted localization in the ventricular regions including the ependymal cilia. The localization of Gα_i2 is conserved in cilia of different tissues, suggesting a particular role in ciliary function. Although studies with Gα_i2-knockout mice have provided information on the role of this Gα subunit in peripheral tissues, its role in the CNS is largely unknown. We used intracerebroventricular (icv) antisense administration to clarify the physiological role of Gα_i2 in the ventricular system.     

The organizational effects of oxytocin on the central expression of estrogen receptor α and oxytocin in adulthood

Background  

Previous studies have demonstrated that neonatal manipulation of oxytocin (OT) has effects on the expression of estrogen receptor α (ERα) and the central production of oxytocin observed in juveniles (at weaning, 21 days of age). The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles (Microtus ochrogaster) received one of three doses of OT (High, 3 μg; Med, 0.3 μg; Low, 0.03 μg), an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ERα or OT using immunocytochemistry.     

Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

Background  

Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α₂-adrenergic receptor (α₂-AR) density in adolescent (35-days-old) rats, using [³H]RX821002 (5 nM).     

Cerebrospinal fluid promotes survival and astroglial differentiation of adult human neural progenitor cells but inhibits proliferation and neuronal differentiation

Background  

Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existing in vitro studies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).     

One-pot synthesis of benzochromeno-pyrazole derivatives

Abstract  

One-pot synthesis of different benzochromeno-pyrazole derivatives has been reported via reaction of aldehydes, 3-methyl-1H-pyrazol-5(4H)-one and α-naphthol/β-naphthol in the presence of sulfamic acid.     

Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism

Background  

High concentrations of glutamate can accumulate in the brain and may be involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. This form of neurotoxicity involves changes in the regulation of cellular calcium (Ca²⁺) and generation of free radicals such as peroxynitrite (ONOO^-). Estrogen may protect against glutamate-induced cell death by reducing the excitotoxic Ca²⁺ influx associated with glutamate excitotoxicity. In this study, the inhibition of N-methyl-D-aspartate (NMDA) receptor and nitric oxide synthase (NOS) along with the effect of 17β-estradiol (17β-E₂) and a more potent antioxidant Δ⁸, 17β-estradiol (Δ⁸, 17β-E₂) on cell viability and intracellular Ca²⁺ ([Ca²⁺]_i), following treatment of rat cortical cells with glutamate, was investigated.     

Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice

Background  

Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype.     

The responses of Ht22 cells to oxidative stress induced by buthionine sulfoximine (BSO)

Background  

glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells. It directly reacts with reactive oxygen species (ROS), functions as a cofactor of antioxidant enzymes, and maintains thiol redox potential in cells. GSH depletion has been implicated in the pathogenesis of neurological diseases, particularly to Parkinson's disease (PD). The purpose of this study was to investigate the change of cellular antioxidant status and basic cell functions in the relatively early stages of GSH depletion.