JWH133 attenuates behavior deficits and iron accumulation in 6-OHDA-induced Parkinson's disease model rats.

Growing evidence indicates that activation of cannabinoid type 2 (CB2) receptors protects dopamine neurons in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying neuroprotection mediated by CB2 receptors are still elusive. In this study, we investigated the effects of CB2 receptor activation on 6-hydroxydopamine (6-OHDA)-induced dopamine neuron degeneration and iron accumulation in the substantia nigra (SN) of rats.

Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice.

Berberine, an isoquinoline alkaloid isolated from , has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, the detailed mechanisms are unknown. In this study, the effects of berberine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease were investigated.

Levo-tetrahydropalmatine inhibits α4β2 nicotinic receptor response to nicotine in cultured SH-EP1 cells.

Nicotine, a major component of tobacco, is highly addictive and acts on nicotinic acetylcholine receptors (nAChRs) to stimulate reward-associated circuits in the brain. It is well known that nAChRs play critical roles in mediating nicotine reward and addiction. Current FDA-approved medications for smoking cessation are the antidepressant bupropion and the nicotinic partial agonist varenicline, yet both are limited by adverse side effects and moderate efficacy.

Therapeutic potential of ATP-sensitive potassium channels in Parkinson's disease.

In the past decade, there was an increasing interest in the therapeutic potential targeting ATP-sensitive potassium (K) channels for an effective treatment of Parkinson's disease (PD). K channels are widely expressed in the central nervous system and were reported to mediate the degeneration and death of nigral dopamine neurons in the pathogenesis of PD. This review aims to address the pivotal roles of K channels played in the mechanisms underlying PD pathogenesis, and provide possible directions for further research from different perspectives, such as the vulnerability of dopamine neurons in the substantia nigra, neurotransmitter releasing, iron metabolism in the brain, α-synuclein secretion and mitochondrial dysfunction, which are off critical importance in the investigation of K channels-targeted precise therapeutic interventions for PD.

Myricetin reduces cytotoxicity by suppressing hepcidin expression in MES23.5 cells.

Multiple studies implicate iron accumulation in the substantia nigra in the degeneration of dopaminergic neurons in Parkinson's disease. Indeed, slowing of iron accumulation in cells has been identified as the key point for delaying and treating Parkinson's disease. Myricetin reportedly plays an important role in anti-oxidation, anti-apoptosis, anti-inflammation, and iron chelation.

JWH133 inhibits MPP-induced inflammatory response and iron influx in astrocytes.

Background: We investigated the anti- inflammatory effect of type II cannabinoid receptor (CB receptor) activation and their relationship to iron influx on 1-methyl-4-phenylpyridinium (MPP) treated astrocytes.

Methods And Results: By western blots, real-time PCR and ELISA, the expressions of CB2 receptor, divalent metal transporter-1 (DMT1), cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF-α) were measured. Iron influx into astrocytes was determined by the quenching of calcein fluorescence.

Berberine alleviates rotenone-induced cytotoxicity by antioxidation and activation of PI3K/Akt signaling pathway in SH-SY5Y cells.

Berberine, an isoquinoline alkaloid isolated from traditional Chinese medicine, has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, berberine-mediated neuroprotection in the pathogenesis of Parkinson's disease is still uncertain. In this study, the effects of berberine on rotenone-induced neurotoxicity in SH-SY5Y cells were investigated.

L-type Calcium Channels are Involved in Iron-induced Neurotoxicity in Primary Cultured Ventral Mesencephalon Neurons of Rats.

In the present study, we investigated the mechanisms underlying the mediation of iron transport by L-type Ca channels (LTCCs) in primary cultured ventral mesencephalon (VM) neurons from rats. We found that co-treatment with 100 µmol/L FeSO and MPP (1-methyl-4-phenylpyridinium) significantly increased the production of intracellular reactive oxygen species, decreased the mitochondrial transmembrane potential and increased the caspase-3 activation compared to MPP treatment alone. Co-treatment with 500 µmol/L CaCl further aggravated the FeSO-induced neurotoxicity in MPP-treated VM neurons.

Cocaine potently blocks neuronal αβ nicotinic acetylcholine receptors in SH-SY5Y cells.

Cocaine is one of the most abused illicit drugs worldwide. It is well known that the dopamine (DA) transporter is its major target; but cocaine also acts on other targets including nicotinic acetylcholine receptors (nAChRs). In this study, we investigated the effects of cocaine on a special subtype of neuronal nAChR, αβ-nAChR expressed in native SH-SY5Y cells.

An unexpected improvement in spatial learning and memory ability in alpha-synuclein A53T transgenic mice.

Growing evidence suggests, as Parkinson's disease (PD) progresses, that its non-motor symptoms appear prior to or in parallel with its motor deficits. Alpha-synuclein A53T transgenic mouse (A53T) is an essential tool to investigate the onsets and the extents of PD non-motor symptoms. Our aim is to investigate spatial learning and memory ability in A53T mice.

Isradipine attenuates MPTP-induced dopamine neuron degeneration by inhibiting up-regulation of L-type calcium channels and iron accumulation in the substantia nigra of mice.

The aim of this study is to investigate the effects of L-type calcium channels (LTCCs) on MPTP-induced dopamine (DA) neuron degeneration and iron accumulation in the substantia nigra (SN) of mice. By real-time PCR and western blots, we first quatified expressions of L-type Cav1.2 and Cav1.

Protective effects of myricetin on chronic stress-induced cognitive deficits.

The aim of the present study is to investigate the possible effects of chronic administration of myricetin, a natural flavonoid, on chronic stress-induced learning and memory deficits in mice. The mice were restrained daily 4 h/day for 21 days in well-ventilated plexiglass tubes without access to food and water. These animals were injected with myricetin or vehicle 40 min before each restraint stress over a period of 21 days.

Quantitative assessment of the association between GAK rs1564282 C/T polymorphism and the risk of Parkinson's disease.

The aim of this meta-analysis was to evaluate the association between cyclin G-associated kinase (GAK) rs1564282 C/T polymorphism and Parkinson's disease (PD) susceptibility. GAK modifies α-synuclein expression levels and affects susceptibility to PD. Genetic variation in GAK may influence the risk of occurrence and progression of PD.

Quantitative assessment of the association between fibroblast growth factor 20 rs1721100 C/G polymorphism and the risk of sporadic Parkinson's diseases: a meta-analysis.

Fibroblast growth factor 20 (FGF20) is a neurotrophic factor which enhances the survival of rat midbrain dopamine neurons. Genetic variation in FGF20 may influence the risk of occurrence and development in Parkinson's diseases (PD). Many studies have evaluated the association between FGF20 rs1721100 C/G polymorphism and the risk of sporadic PD; however, published data are still controversial.

HLA-DRA rs3129882 A/G polymorphism was not a risk factor for Parkinson's disease in Chinese-based populations: a meta-analysis.

Purpose: Many studies have evaluated the association between the HLA-DRA rs3129882 A/G polymorphism and risk for Parkinson's disease (PD) in Chinese-based populations, however, published data remain inconclusive. Therefore, we performed a meta-analysis from all relevant studies to evaluate an association of HLA-DRA rs3129882 A/G polymorphism with susceptibility to PD.

Methods: The summary odds ratio (OR) with its 95% confidence interval (CI) was calculated to evaluate the association.

Transplantation of mouse CGR8 embryonic stem cells producing GDNF and TH protects against 6-hydroxydopamine neurotoxicity in the rat.

Embryonic stem cells (ESCs)-based therapies have been increasingly recognized as a potential tool to replace or support cells and their function damaged by the neurodegenerative process that underlies Parkinson's disease (PD). In this study, we implanted engineered mouse embryonic stem (ES) CGR8 cells, which stably co-express glial cell line-derived neurotrophic factor (GDNF) and tyrosine hydroxylase (TH), into striatum (Str) or both Str and substantia nigra (SN) of parkinsonian rats lesioned by 6-hydroxydopamine (6-OHDA). We found that cell transplantation into Str or both Str and SN rescued behavioral abnormalities and striatal DA depletion associated with 6-OHDA lesion.

Flavonoid Myricetin Modulates GABA(A) Receptor Activity through Activation of Ca(2+) Channels and CaMK-II Pathway.

The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABA(A) receptor.

Myricetin facilitates potassium currents and inhibits neuronal activity of PVN neurons.

The effects of myricetin on hypothalamic paraventricular nucleus (PVN) neurons in rats were investigated. By whole-cell patch clamp detection in hypothalamic brain slices, we showed that the action potential frequency in type-I PVN neurons dose-dependently decreased after myricetin treatment. Further studies demonstrated that myricetin may enhance potassium currents and shifts the voltage-dependence of activation of potassium currents to more negative potentials by 6.

Nifedipine prevents iron accumulation and reverses iron-overload-induced dopamine neuron degeneration in the substantia nigra of rats.

The mechanisms of iron accumulation in substantia nigra (SN) of Parkinson's diseases remain unclear. The objective of this study was to investigate effects of nifedipine on iron-overload-induced iron accumulation and neurodegeneration in SN of rats. By high performance liquid chromatography-electrochemical detection, tyrosine hydroxylase (TH) immunohistochemistry, and iron content array, we first quantified iron content and the number of dopamine neurons in SN of experimental rats treated with iron dextran.

Mitochondria dysfunction was involved in copper-induced toxicity in MES23.5 cells.

Objective: To investigate the toxicity of copper on MES23.5 dopaminergic cells and the probable mechanisms involved in this process.

Methods: MES23.

Myricetin reduces 6-hydroxydopamine-induced dopamine neuron degeneration in rats.

The effects of myricetin on 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in the substantia nigra-striatum system were investigated. By high-performance liquid chromatography electrochemical detection, we showed that the dopamine content in the striatum decreased after 6-OHDA treatment, which could be restored by myricetin. The immunohistochemistry and semiquantitative reverse transcription-PCR studies showed that myricetin could prevent the 6-OHDA-induced decrease of tyrosine hydroxylase positive neurons and the tyrosine hydroxylase mRNA expression in the substantia nigra.

Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing capacity and male fertility.

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl(-) and HCO(3)(-) transport. Although >95% of all CF male patients are infertile because of congenital bilateral absence of the vas deferens (CBAVD), the question whether CFTR mutations are involved in other forms of male infertility is under intense debates. Here we report that CFTR is detected in both human and mouse sperm.

C31 enhances voltage-gated calcium channel currents in undifferentiated PC12 cells.

C31, consisting of 31 amino acid residues, is generated from the carboxyl terminal fragments (CTFs) of amyloid precursor protein (APP). It has been shown that C31 causes apoptosis in neurons and is present in brains of Alzheimer disease (AD) patients. Using whole-cell patch clamp techniques, we investigated effects of C31 on voltage-gated calcium channel (VGCC) currents and the protective effects of beta-estradiol on PC12 cells.