β-Caryophyllene mitigates ischemic stroke-induced white matter lesions by inhibiting pyroptosis.

β-Caryophyllene (BCP), a selective agonist for cannabinoid receptor 2 (CB2R), has demonstrated promising protective effects in various pathological conditions. However, the neuroprotective effects of BCP on white matter damage induced by ischemic stroke have not been elucidated previously. In this study, we find that BCP not only improves sensorimotor and cognitive function via CB2R but also mitigates white matter lesions in mice following ischemic stroke.

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.

Cannabinoid type 2 receptor activation inhibits MPP-induced M1 differentiation of microglia through activating PI3K/Akt/Nrf2 signal pathway.

Background: Growing evidence indicates that cannabinoid type 2 (CB2) receptor activation inhibits neuroinflammation in the pathogenesis of Parkinson's disease (PD). Nonetheless, the precise mechanisms of CB2 receptor-mediated neuroprotection have not been fully elucidated. The differentiation of microglia from the M1 to M2 phenotype plays a vital role in neuroinflammation.

Roles of the Cannabinoid System in the Basal Ganglia in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease usually caused by neuroinflammation, oxidative stress and other etiologies. Recent studies have found that the cannabinoid system present in the basal ganglia has a strong influence on the progression of PD. Altering the cannabinoid receptor activation status by modulating endogenous cannabinoid (eCB) levels can exert an anti-movement disorder effect.

Attribute nonattendance in COVID-19 vaccine choice: A discrete choice experiment based on Chinese public preference.

Objectives: The global coronavirus disease 2019 (COVID-19) pandemic has not been well controlled, and vaccination could be an effective way to prevent this pandemic. By accommodating attribute nonattendance (ANA) in a discrete choice experiment (DCE), this paper aimed to examine Chinese public preferences and willingness to pay (WTP) for COVID-19 vaccine attributes, especially the influence of ANA on the estimated results.

Methods: A DCE was designed with four attributes: effectiveness, protection period, adverse reactions and price.

Scope Issue in Contingent Valuation Studies of the COVID-19 Vaccine: The Case of China.

Background: Assessing the public's willingness to pay (WTP) for the coronavirus disease 2019 (COVID-19) vaccine by the contingent valuation (CV) method can provide a relevant basis for government pricing. However, the scope issue of the CV method can seriously affect the validity and reliability of the estimation results.

Aim: To examine whether there are scope issues in respondents' WTP for the COVID-19 vaccine and to further verify the validity and reliability of the CV estimate results.

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.

Cannabinoid CB receptors are expressed in glutamate neurons in the red nucleus and functionally modulate motor behavior in mice.

Cannabinoids produce a number of central nervous system effects via the CB receptor (CBR), including analgesia, antianxiety, anti-reward, hypoactivity and attenuation of opioid-induced respiratory depression. However, the cellular distributions of the CBRs in the brain remain unclear. We have reported that CBRs are expressed in midbrain dopamine (DA) neurons and functionally regulate DA-mediated behavior(s).

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.

Activation of cannabinoid receptor 2 protects rat hippocampal neurons against Aβ-induced neuronal toxicity.

Alzheimer's disease (AD) is a dementing, neurodegenerative disorder characterized by increased accumulation of beta-amyloid peptides (Aβ), degeneration of hippocampal neurons and the gradual development of learning and memory deficits. Therapeutically, there are still no ideal medicines available and this represents an urgent need for the development of new strategies to treat AD. Emerging lines of evidence suggest that modulation of the cannabinoid system exhibits neuroprotective effects in various neurological diseases, including AD.

Effects of ghrelin on the electrical activities of substantia nigra dopaminergic neurons treated with MPP.

Ghrelin, a 28 amino acid brain-gut peptide, has attracted increasing attention for its neuroprotective effect in Parkinson's disease (PD). In view of the pivotal role of excitability of dopaminergic neurons in substantia nigra pars compacta (SNc) in the function of nigrostriatal system, it is of great significance to elucidate the regulation of electrical activity of dopaminergic neurons by ghrelin, especially in PD pathogenesis. In this study, we tackled this issue by probing the effects of ghrelin on the electrophysiological properties of dopaminergic neurons in acute application of Methyl-4-phenylpyridinium (MPP), a potent parkinsonizing agent in primates and rodents, with whole cell patch clamp technique.

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.

Mechanisms of cannabinoid CB receptor-mediated reduction of dopamine neuronal excitability in mouse ventral tegmental area.

Background: We have recently reported that activation of cannabinoid type 2 receptors (CBRs) reduces dopamine (DA) neuron excitability in mouse ventral tegmental area (VTA). Here, we elucidate the underlying mechanisms.

Methods: Patch-clamp recordings were performed in mouse VTA slices and dissociated single VTA DA neurons.

Cocaine Directly Inhibits α6-Containing Nicotinic Acetylcholine Receptors in Human SH-EP1 Cells and Mouse VTA DA Neurons.

Alpha6-containing nicotinic acetylcholine receptors are primarily found in neurons of the midbrain dopaminergic (DA) system, suggesting these receptors are potentially involved in drug reward and dependence. Here, we report a novel effect that cocaine directly inhibits α6N/α3Cβ2β3-nAChR (α6*-nAChRs) function. Human α6*-nAChRs were heterologously expressed within cells of the SH-EP1 cell line for functional characterization.

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.

The 2-aminoethoxydiphenyl borate analog, DPB161 blocks store-operated Ca entry in acutely dissociated rat submandibular cells.

Cellular Ca signals play a critical role in cell physiology and pathology. In most non-excitable cells, store-operated Ca entry (SOCE) is an important mechanism by which intracellular Ca signaling is regulated. However, few drugs can selectively modulate SOCE.

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.

Myricetin Attenuates Depressant-Like Behavior in Mice Subjected to Repeated Restraint Stress.

Increasing evidence has shown that oxidative stress may be implicated in chronic stress-induced depression. Several flavonoids with anti-oxidative effects have been proved to be anti-depressive. Myricetin is a well-defined flavonoid with the anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective properties.

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.