Differential alteration of dopamine, acetylcholine, and glutamate release during anoxia and/or 3,4-diaminopyridine treatment

Abstract

The potassium-stimulated release of acetylcholine (ACh), glutamate (GLU) and dopamine (DA) from mouse striatal slices was studied during anoxia and/or 3,4-diaminopyridine (DAP) treatment. Anoxia, in the presence of calcium, increased DA and GLU release, but depressed ACh release. Omission of calcium from an anoxic incubation further stimulated GLU and DA release and impaired ACh release. Under normoxic conditions, DAP (100 microM) increased the release of all three neurotransmitters; the sensitivity of the slices to DAP changed with the presence or absence of an acetylcholinesterase inhibitor in the preincubation media. During an anoxic incubation, DAP did not ameliorate the anoxic-induced, K+-stimulated impairment of ACh release, but significantly reduced the K+-stimulated release of GLU and DA. These results are consistent with the hypothesis that hypoxia induces a presynaptic deficit that may underlie postsynaptic ischemic-induced changes. Amelioration of these presynaptic alterations in neurotransmitter release may be an effective approach to preventing hypoxic-induced damage.

Cerebrometabolic Aspects of Delirium in Relationship to Dementia

“…Cholinergic transmission turns out to be exquisitely sensitive to impairments of cerebral metabolism, despite the two to three order of magnitude differences in fluxes of carbon to CO 2 and to acetylcholine. Results were similar in vitro and in vivo, and with several different types of experimental preparations [5][6][7]. The oxygen tensions associated with decreased acetylcholine synthesis in mice are those associated with impaired judgement in humans [2,6].…”

“…For instance, hypoxia leads to an increase in the release of potentially neurotoxic neurotransmitters including gluta- mate [7]. This finding provides a mechanism by which delirium could also lead to the permanent brain damage characteristic of dementia.…”

“…A functional connection between the metabolic encephalopathies and disorders of neurotransmission was uncovered by our coworkers and us in the 1970s [4][5][6][7]. Cholinergic transmission turns out to be exquisitely sensitive to impairments of cerebral metabolism, despite the two to three order of magnitude differences in fluxes of carbon to CO 2 and to acetylcholine.…”

“…Metabolic encephalopathies may also be related to excitotoxic damage and death of neurons [7]. For instance, hypoxia leads to an increase in the release of potentially neurotoxic neurotransmitters including gluta- mate [7].…”

Frequency, Risk Factors, and Prognosis of Prolonged Delirium in Elderly Patients After Hip Fracture Surgery

“…Five of eight (62.5%) patients in the prolonged delirium group who were able to ambulate outdoors were housebound at final followup (p = 0.003). similar causative factors, such as excitotoxic neuronal damage and neuron death [1,5,11].…”