Overview Topics

Neurotoxicity and cytokines


A summary of some of the known interactions between cytokines, cells, and factors that are implicated in neurotoxicity and neural death is given below. Numbers in the figures refer to citations (given below). These will eventually be incorporated in the simulation.


Astrocyte secretion of cytokines


Note the effect on glutamine synthetase (found only in astrocytes) which is one of the factors protecting neurons from glutamate induced excitotoxicity. [1]


[1] Chao CC, Hu S, Tsang M, Weatherbee J, Molitor TW, Anderson WR, Peterson PK (1992). Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury. J Clinical Investigation 90(5): 1786-93.Abstract


NMDA-receptor excitotoxicity



Note: the effect of excitotoxicity on neurons is to decrease the activity of choline acetyl transferase (ChAT) in cholinergic neurons and to decrease the activity of glutamate decarboxylase (GAD) in GABAergic neurons. IL-6 (10 units) reduces the first effect, but not the second.

[2] Toulmond S, Vige X, Fage D, Benavides J (1992). Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. Neurosci Letters 144(1-2):49-52.Abstract

Effects of IL-6 on Glutamate and NMDA induced excitotoxicity


Remarks: IL-6 appears to have multiple effects, some neuroprotective, and others damaging. The effects depend on the duration of exposure and the cell type [6]. IL-6 is known to protect from NMDA induced excitotoxicity under some conditions [7], but to elevate calcium currents that can lead to increased neuronal stress/death in other cases [3]. 

[3] Qiu Z, Sweeney DD, Netzeband J G, Gruol D L (1998). Chronic interleukin-6 alters NMDA receptor mediated membrane responses and enhances neurotoxicity in developing CNS neurons. J Neurosci 18(24):10445-56. Abstract

[3b] Conroy S M, Gruol D L (1997). The cytokine IL-6 enhances neurotoxicity involving NMDA receptors in developing central nervous system neurons. NCWH Abstracts archive, 1997.


Effects of TGF-beta on astrocytes




[4] Tarkowski E, Blennow K, Wallin A, Tarkowski A. (1999) Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent in Alzheimer's disease and vascular dementia. J Clinical Immunol 19(4): 223-30. Abstract

[5] Orzylowska O, Oderfeld-Nowak B, Zaremba M, Januszewski S, Mossakowski M (1999). Prolonged and concomitant induction of astroglial immunoreactivity of interleukin 1beta and interleukin-6 in the rat hippocampus after transient global ischemia. Neurosci Lett 263(1):72-6. Abstract

[6] Hull M, Eistetter J, Fiebich B L, Bauer J (1999). Glutamate but not interleukin-6 influences the phosphorylation of tau in primary rat hippocampal neurons. Neurosci Lett 261 (1-2):33-6.Abstract

[7] Brown DR (1999). Dependence of neurons on astrocytes in a co-culture system renders neurons sensitive to transforming growth factor beta 1 induced glutamate toxicity. J Neurochemistry 72(3):943-53. Abstract


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