Astrocyte glutamate neuron dopamine

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine-producing neurons in the substantia nigra and the abnormal cytoplasmic accumulation of proteinaceous aggregates called Lewy bodies (LBs), mainly composed of α-synuclein (α-syn). In recent years, it has been gradually recognized that fatigue is one of the most common and disabling symptoms in PD patients, with a prevalence of approximately 50%. Although neuroinflammation, a pathological hallmark of PD, is closely associated with fatigue, present mechanisms of fatigue in PD patients have not yet been systematically summarized, with their inflammatory predictors remaining controversial...

Human menstrual blood-derived mesenchymal stromal cells (MenSCs) have become not only an important source of stromal cells for cell therapy but also a cellular source for neurologic disorders in vitro modeling. By using culture protocols originally developed in our laboratory, we show that MenSCs can be converted into floating neurospheres (NSs) using the Fast-N-Spheres medium for 24-72 h and can be transdifferentiated into functional dopaminergic-like (DALNs, ~ 26% TH + /DAT + flow cytometry) and cholinergic-like neurons (ChLNs, ~ 46% ChAT + /VAChT flow cytometry) which responded to dopamine- and acetylcholine-triggered neuronal Ca2+ inward stimuli when cultured with the NeuroForsk and the Cholinergic-N-Run medium, respectively in a timely fashion (i...

Neurotransmitter transporters limit spillover between synapses and maintain the extracellular neurotransmitter concentration at low yet physiologically meaningful levels. They also exert a key role in providing precursors for neurotransmitter biosynthesis. In many cases, neurons and astrocytes contain a large intracellular pool of transporters that can be redistributed and stabilized in the plasma membrane following activation of different signaling pathways. This means that the uptake capacity of the brain neuropil for different neurotransmitters can be dynamically regulated over the course of minutes, as an indirect consequence of changes in neuronal activity, blood flow, cell-to-cell interactions, etc...

Astrocytes and microglia are brain-resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases...

Efficacious pharmacotherapies for the treatment of substance use disorders need to be expanded and improved. Non-neuronal cells, particularly astrocytes and microglia, have emerged as therapeutic targets for the development of pharmacotherapies to treat dependence and relapse that accompanies chronic drug use. Cytokines and chemokines are neuroimmune factors expressed in neurons, astrocytes, and microglia that demonstrate promising clinical utility as therapeutic targets for substance use disorders. In this review, we describe a role for cytokines and chemokines in the rewarding and reinforcing effects of alcohol, opioids, and psychostimulants...

Diabetic brain is a serious complication of diabetes, and it is associated with oxidative stress and neuronal injury. This study investigated the protective effect of melatonin (MLT) on diabetes-induced brain injury. A rat model of type 2 diabetes mellitus was produced by intraperitoneal injection of nicotinamide 100 mg/kg, followed by intraperitoneal injection of streptozotocin 55 mg/kg. The diabetic rats were orally administered MLT 10 mg/kg of body weight for 15 days. MLT remarkably downregulated serum glucose levels...

The initial exploration using pharmacological tools of the role of adenosine receptors in the brain, concluded that adenosine released as such acted on A1 R to inhibit excitability and glutamate release from principal neurons throughout the brain and that adenosine A2A receptors (A2A R) were striatal-'specific' receptors controlling dopamine D2 R. This indicted A1 R as potential controllers of neurodegeneration and A2A R of psychiatric conditions. Global knockout of these two receptors questioned the key role of A1 R and instead identified extra-striatal A2A R as robust controllers of neurodegeneration...

Astrocytes are a major constituent of the central nervous system (CNS). Astrocytic oxidative stress contributes to the development of Parkinson's disease (PD). Maintaining production of antioxidant and detoxification of reactive oxygen and nitrogen species (ROS/RNS) in astrocytes is critical to prevent PD. Study has illuminated that ascorbic acid (AA) stimulates dopamine synthesis and expression of tyrosine hydroxylase in human neuroblastoma cells. However, the role and regulatory mechanisms of AA on detoxification of astrocytes are still unclear...

Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoimmune antibodies. RESULTS: Studying 30 South Sudanese NS patients and a similar number of healthy subjects from the same geographical region, revealed autoimmune antibodies to 3 extracellular peptides of ionotropic glutamate receptors in NS patients: AMPA-GluR3B peptide antibodies (86%), NMDA-NR1 peptide antibodies (77%) and NMDA-NR2 peptide antibodies (87%) (in either 1:10, 1:100 or 1:1000 serum dilution)...

Neurological diseases particularly Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and epilepsy are on the rise all around the world causing morbidity and mortality globally with a common symptom of gradual loss or impairment of motor behaviour. Striatum, which is a component of the basal ganglia, is involved in facilitating voluntary movement while the cerebellum is involved in the maintenance of balance and coordination of voluntary movements. Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate, to name a few, interact in regulating the excitation and inhibition of motor neurons...

There are reports that depression induced by frontal lobe injury (FLI) has a devastating effect on human mental health. We previously reported that fasciculation and elongation protein zeta-1 (FEZ1) was essential for astrocytic protection of dopamine neurons. Studies of glutamate-glutamine cycle in mental illness have been reported, whereas not from the perspective of astrocytes. This study was designed to investigate the roles of astrocytic FEZ1 and glutamate-glutamine cycle after FLI. A model of FLI was established by inserting a blade into the right frontal lobe of rats...

The lifetime prevalence of addiction to cannabis (marijuana or cannabinoids) is among the highest of that of all illicit drugs in developed countries, and no effective treatment for cannabis addiction is currently available. Previous studies in our research group suggested that astrocyte-mediated long-term depression (LTD) in ventral tegmental area (VTA) dopamine neurons plays a pivotal role in the development of cannabis addiction. The present study was designed to investigate the effects and potential mechanisms of riluzole, a drug used for the treatment of motor neuron diseases, on cannabinoid-facilitated LTD induction...

The transition from recreational drug use to compulsive drug seeking habits, the hallmark of addiction, has been shown to depend on a shift in the locus of control over behaviour from the ventral to the dorsolateral striatum. This process has hitherto been considered to depend on the aberrant engagement of dopamine-dependent plasticity processes within neuronal networks. However, exposure to drugs of abuse also triggers cellular and molecular adaptations in astrocytes within the striatum which could potentially contribute to the intrastriatal transitions observed during the development of drug addiction...

The ventral tegmental area (VTA) is a heterogeneous midbrain structure, containing neurons and astrocytes, that coordinates behaviors by integrating activity from numerous afferents. Within neuron-astrocyte networks, astrocytes control signals from distinct afferents in a circuit-specific manner, but whether this capacity scales up to drive motivated behavior has been undetermined. Using genetic and optical dissection strategies we report that VTA astrocytes tune glutamatergic signaling selectively on local inhibitory neurons to drive a functional circuit for learned avoidance...

BACKGROUND AND PURPOSE: Purinergic P2X7 receptors are present on neurons, astrocytes and microglia and activated by extracellular ATP. Since P2X7 receptor activation releases endogenous substrates (e.g., pro-inflammatory cytokines, dopamine, and glutamate) that facilitate psychostimulant reward and reinforcement, we investigated the hypothesis that the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) produces rewarding effects that are dependent on active P2X7 receptors. METHODS: Reward function was measured in male mice using intracranial self-stimulation (ICSS)...

Parkinson's disease (PD) features the degeneration and death of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies that contain alpha-synuclein (α-Syn). Among the numerous PD etiologies, glutamate excitotoxicity is a research hotspot, and glutamate transporters play key roles in this theory. It has been shown that the expression of glutamate transporter is regulated by microRNAs. In this study, we found that the expression and function of glutamate transporter type one (GLT-1) were significantly reduced and miR-543-3p was upregulated during the development of PD...

BACKGROUND: Dysregulation of arousal is symptomatic of numerous psychiatric disorders. Previous research has shown that the activity of dopamine (DA) neurons in the ventral periaqueductal gray (vPAG) tracks with arousal state, and lesions of vPAGDA cells increase sleep. However, the circuitry controlling these wake-promoting DA neurons is unknown. METHODS: This study combined designer receptors exclusively activated by designer drugs (DREADDs), behavioral pharmacology, electrophysiology, and immunoelectron microscopy in male and female mice to elucidate mechanisms in the vPAG that promote arousal...

The reinforcing effects of Δ9 -tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of α7 nicotinic acetylcholine receptors (α7nAChRs) and is synthesized and released by astroglia, which express functional α7nAChRs and cannabinoid CB1 receptors (CB1Rs)...

Tau hyperphosphorylation is a critical factor in neurodegenerative diseases, including dementia and Parkinsonism. Existing animal models of tauopathies express tau in neurons within the forebrain and do not often show tau accumulation in the brainstem and astrocytes. This study aims to understand the effects of differential regional expression of tau on neurotransmitter balance in the brain. To obtain an animal model that expresses tau in the brainstem, we bred hemizygous mice that express P301L tau (TauP301L) and detected hyper-phosphorylated tau (p-tau) predominantly in the hippocampus, cortex, brainstem and thalamus...

Astrocytes are ubiquitous CNS cells that support tissue homeostasis through ion buffering, neurotransmitter recycling, and regulation of CNS vasculature. Yet, despite the essential functional roles they fill, very little is known about the physiology of astrocytes in the ventral midbrain, a region that houses dopamine-releasing neurons and is critical for reward learning and motivated behaviors. Here, using a combination of whole-transcriptome sequencing, histology, slice electrophysiology, and calcium imaging, we performed the first functional and molecular profiling of ventral midbrain astrocytes and observed numerous differences between these cells and their telencephalic counterparts, both in their gene expression profile and in their physiological properties...