Studies of Nmda- And Non-Nmda-Mediated Neurotoxicity in Cultured Neurons

Deupree, David L.; Tang, Xiao Wen; Yarom, Mina; Dickman, E.J.; Kirch, R.D; Schloss, John V.; Wu, Jang‐Yen

doi:10.1016/0197-0186(96)00003-4

Cited by 21 publications

(14 citation statements)

References 30 publications

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“…This conclusion is based on the following observations: 1) it is generally accepted that Glu-induced neurotoxicity is due to the disruption of intracellular calcium homeostasis resulting in elevation of intracellular free calcium, [Ca 2ϩ ] i (Rothman and Olney, 1986;Choi, 1988;McDonald and Johnston, 1990;Deupree et al, 1996); 2) fullerenols reduce Glu-induced increase of [Ca 2ϩ ] i markedly and rapidly (Fig. 3); 3) fullerenols prevent Glu-induced elevation of [Ca 2ϩ ] i if neurons are pre-incubated with fullerenols (Fig.…”

Section: Discussionmentioning

confidence: 99%

Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Ji¹,

Chen²,

Tang³

et al. 2000

J. Neurosci. Res.

147

101

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Section: Discussionmentioning

confidence: 99%

Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Ji¹,

Chen²,

Tang³

et al. 2000

J. Neurosci. Res.

147

101

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“…However, AMPA͞kainate receptors flux large amounts of sodium, which can depolarize cell membranes. Such depolarization may activate both voltage-sensitive calcium channels (21) and facilitate NMDAr activation (22,23). In this way, AMPA͞kainate receptor stimulation may lead indirectly to accumulation of toxic intracellular calcium levels.…”

Section: Resultsmentioning

confidence: 99%

Cannabidiol and (−)Δ ⁹ -tetrahydrocannabinol are neuroprotective antioxidants

Hampson

Grimaldi

Axelrod

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

765

529

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The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (؊)⌬ 9 -tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptorinduced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid͞kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or ␣-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.Cannabinoid components of marijuana are known to exert behavioral and psychotropic effects but also to possess therapeutic properties including analgesia (1), ocular hypotension (2), and antiemesis (3). This report examines another potential therapeutic role for cannabinoids as neuroprotectants and describes their mechanism of action in rat cortical neuronal cultures.During an ischemic episode, large quantities of the excitatory neurotransmitter glutamate are released. This event causes neuronal death by over-stimulating N-methyl-Daspartate receptors (NMDAr) and 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid (AMPA) and kainatetype receptors and results in metabolic stress and accumulation of toxic levels of intracellular calcium (4). In vitro and in vivo studies (4,5,6) have demonstrated that such neurotoxicity can be reduced by antioxidants or antagonists to NMDAr and AMPA͞kainate receptors. Antioxidants such as ␣-tocopherol (5, 6) are effective neuroprotectants because of their ability to reduce the toxic reactive oxygen species (ROS) formed during ischemic metabolism. Cannabinoids like (Ϫ)⌬ 9

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“…L-Glu-induced neurotoxicity was studied in neuronal cultures at 14 DIV as described previously [5]. Prior to Glu treatment, the original culture media were replaced with fresh serum-free GME and the cultures were equilibrated in the incubator for 2 h. The experiments were carried out at room temperature in an environmental hood.…”

Section: Treatment Of Neuronal Cultures With Glutamate or Acmentioning

confidence: 99%

“…The preparation of cell suspensions and the measurement of LDH were the same as described [5]. Change of absorbance at 340 nm upon addition of ß-NADH was used for the determination of LDH activities.…”

Section: Determination Of Neuronal Damage By Lactate Dehydrogenase Assaymentioning

confidence: 99%

Neurotoxic Effect of Acamprosate, N-Acetyl-Homotaurine, in Cultured Neurons

Jin

Schloss

et al. 2001

J Biomed Sci

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Acamprosate (AC), N-acetyl-homotaurine, has recently been introduced for treating alcohol craving and reducing relapses in weaned alcoholics. AC may exert its action through the taurine system rather than the glutamatergic or GABAergic system. This conclusion is based on the observations that AC strongly inhibits the binding of taurine to taurine receptors while it has little effect on the binding of glutamate to glutamate receptors or muscimol to GABA_A receptors. In addition, AC was found to be neurotoxic, at least in neuronal cultures, triggering neuronal damage at 1 mM. The underlying mechanism of AC-induced neuronal injury appears to be due to its action in increasing the intracellular calcium level, [Ca²⁺]_i. Both AC-induced neurotoxicity and elevation of [Ca²⁺]_i can be prevented by taurine suggesting that AC may exert its effect through its antagonistic interaction with taurine receptors.

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Studies of Nmda- And Non-Nmda-Mediated Neurotoxicity in Cultured Neurons

Cited by 21 publications

References 30 publications

Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Cannabidiol and (−)Δ ⁹ -tetrahydrocannabinol are neuroprotective antioxidants

Neurotoxic Effect of Acamprosate, N-Acetyl-Homotaurine, in Cultured Neurons

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Studies of Nmda- And Non-Nmda-Mediated Neurotoxicity in Cultured Neurons

Cited by 21 publications

References 30 publications

Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants

Neurotoxic Effect of Acamprosate, N-Acetyl-Homotaurine, in Cultured Neurons

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Cannabidiol and (−)Δ ⁹ -tetrahydrocannabinol are neuroprotective antioxidants