ArticleMolecular neurobiology2016
Crosstalk Among Disrupted Glutamatergic and Cholinergic Homeostasis and Inflammatory Response in Mechanisms Elicited by Proline in Astrocytes.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder.Molecular psychiatry · 2021Pooled it
- Uptake of L-proline by Cultured Primary Rat Astrocytes.Neurochemical research · 2026Article
- Consumption of L-Proline as Energy Substrate by Cultured Primary Rat Astrocytes.Neurochemical research · 2025Article
- Metabolomic Profiling Reveals Distinct Plasma Metabolic Signatures in Acne Patients with and without Depression.Clinical, cosmetic and investigational dermatology · 2025Article
- Exogenous Substrates Prevent the Decline in the Cellular ATP Content of Primary Rat Astrocytes During Glucose Deprivation.Neurochemical research · 2024Article
- A Shifted Urinary Microbiota Associated with Disease Activity and Immune Responses in Rheumatoid Arthritis.Microbiology spectrum · 2023Article
- Effect of Proline on Cell Death, Cell Cycle, and Oxidative Stress in C6 Glioma Cell Line.Neurotoxicity research · 2021Article
- Neurobiological perspective of 22q11.2 deletion syndrome.The lancet. Psychiatry · 2019Review
- Synergistic Toxicity of the Neurometabolites Quinolinic Acid and Homocysteine in Cortical Neurons and Astrocytes: Implications in Alzheimer's Disease.Neurotoxicity research · 2018Article
- Neurotoxicity of Methylmercury in Isolated Astrocytes and Neurons: the Cytoskeleton as a Main Target.Molecular neurobiology · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperprolinemias are inherited disorder of proline (Pro) metabolism. Patients affected may present neurological manifestations, but the mechanisms of neural excitotoxicity elicited by hyperprolinemia are far from being understood. Considering that the astrocytes are important players in neurological disorders, the aim of the present work was to study the effects 1 mM Pro on glutamatergic and inflammatory parameters in cultured astrocytes from cerebral cortex of rats, exploring some molecular mechanisms underlying the disrupted homeostasis of astrocytes exposed to this toxic Pro concentration. We showed that cortical astrocytes of rats exposed to 1 mM Pro presented significantly elevated extracellular glutamate and glutamine levels, suggesting glutamate excitotoxicity. The excess of glutamate elicited by Pro together with increased glutamate uptake and upregulated glutamine synthetase (GS) activity supported misregulated glutamate homeostasis in astrocytic cells. High Pro levels also induced production/release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. We also evidenced misregulation of cholinergic anti-inflammatory system with increased acetylcholinesterase (AChE) activity and decreased acetylcholine (ACh) levels, contributing to the inflammatory status in Pro-treated astrocytes. Our findings highlighted a crosstalk among disrupted glutamate homeostasis, cholinergic mechanisms, and inflammatory cytokines, since ionotropic (DL-AP5 and CNQX) and metabotropic (MCPG and MPEP) glutamate antagonists were able to restore the extracellular glutamate and glutamine levels; downregulate TNFα and IL6 production/release, modulate GS and AChE activities; and restore ACh levels. Otherwise, the non-steroidal anti-inflammatory drugs nimesulide, acetylsalicylic acid, ibuprofen, and diclofenac sodium decreased the extracellular glutamate and glutamine levels, downregulated GS and AChE activities, and restored ACh levels in Pro-treated astrocytes. Altogether, our results evidence that the vulnerability of metabolic homeostasis in cortical astrocytes might have important implications in the neurotoxicity of Pro.
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