Lapin followed up this research by demonstrating that quinolinic acid could induce convulsions when injected into mice brain ventricles.

The quinolinic acid produced in microglia is then released and stimulates NMDA receptors, resulting in excitatory neurotoxicity.

It is suspected that this is a result of activation of indoleamine dioxygenases (to be specific, IDO-1 and IDO-2) as well as tryptophan 2,3-dioxygenase (TDO) stimulation by inflammatory cytokines (mainly IFN-gamma, but also IFN-beta and IFN-alpha).

High levels of Ca2+ in the neuron trigger an activation of destructive enzymatic pathways including protein kinases, phospholipases, NO synthase, and proteases.

Quinolinic acid can interact with Fe(II) to form a complex that induces a reactive oxygen and nitrogen species (ROS/RNS), notably the hydroxyl radical •OH.

This free radical causes oxidative stress by further increasing glutamate release and inhibiting its reuptake, and results in the breakdown of DNA in addition to lipid peroxidation.

[14] Quinolinic acid has also been noted to increase phosphorylation of proteins involved in cell structure, leading to destabilization of the cytoskeleton.

[16] Increased levels of quinolinic acid might contribute to the apoptosis of astrocytes and certain neurons, resulting in decreased synthesis of neurotrophic factors.

In addition, increased levels of quinolinic acid could play a role in impairment of the glial-neuronal network, which could be associated with the recurrent and chronic nature of depression.

For instance, when quinolinic acid levels are increased, mice socialize and groom for shorter periods of time.

[11][15] The cytotoxic effects of quinolinic acid elaborated upon in the toxicity section amplify cell death in neurodegenerative conditions.

Studies have demonstrated that quinolinic acid leads to depolarization of spinal motor neurons by interacting with the NMDA receptors on those cells in rats.

Following cerebral ischaemia, delayed neuronal death may occur in part because of central microglia and macrophages, which possess and secrete quinolinic acid.

[19] Studies have found that there is a correlation between levels of quinolinic acid in cerebral spinal fluid (CSF) and HIV-associated neurocognitive disorder (HAND) severity.

[21] Neurons exposed to quinolinic acid for long periods of time can develop cytoskeletal abnormalities, vacuolization, and cell death.

Furthermore, studies in rats have demonstrated that quinolinic acid can lead to neuronal death in brains structures that are affected by HAND, including the striatum, hippocampus, the substantia nigra, and non-limbic cortex.

[20] Levels of quinolinic acid in the CSF of AIDS patients with AIDS- dementia can be up to twenty times higher than normal.

Similar to HIV patients, this increased quinolinic acid concentration correlates with cognitive and motor dysfunction.

[21] In the initial stages of Huntington's disease, patients have substantially increased quinolinic acid levels, in particular in the neostriatum and cortex.

[17][22] Studies show that quinolinic acid is involved in the degeneration of the dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease patients.

Microglia associated with dopaminergic cells in the SN produce quinolinic acid at this location when scientists induce Parkinson's disease symptoms in macaques.

NMDAr antagonists have been shown to provide protection to motor neurons from excitotoxicity resulting from quinolinic acid production.

[23] This change in balance has the potential to reduce hyperexcitability, and thus excitotoxic damage produced from elevated levels of quinolinic acid.

[23] Therapeutic efforts are also focusing on antioxidants, which have been shown to provide protection against the pro-oxidant properties of quinolinic acid.

[10] Norharmane suppresses the production of quinolinic acid, 3-hydroxykynurenine and nitric oxide synthase, thereby acting as a neuroprotectant.

[24] Natural phenols such as catechin hydrate, curcumin, and epigallocatechin gallate reduce the neurotoxicity of quinolinic acid, via anti-oxidant and possibly calcium influx mechanisms.