Elsevier

Neuroscience

Volume 7, Issue 7, July 1982, Pages 1771-1778
Neuroscience

Post-mortem high affinity glutamate uptake in human brain

https://doi.org/10.1016/0306-4522(82)90034-3Get rights and content

Abstract

High-affinity uptake of the putative excitatory neurotransmitter glutamate was examined in human brain tissue collected at autopsy. Uptake characteristics were determined in crude synaptosomal (P2) fractions prepared under varying conditions of tissue storage. Portions of the P2 fractions were also examined by electron-microscopy. Both neurochemical and morphological features were compared with equivalent measures from fresh rat brain tissue. The data demonstrate the presence of sodium-dependent uptake sites for glutamate in the human specimens. Accumulation of the amino acid is abolished by sonicating the P2 suspension prior to incubation, indicating the dependency of the process on the integrity of brain elements. Frozen tissue samples can be stored up to three months without appreciable changes in experimental data. However, samples prepared from tissue which has been dissected and frozen 15–28 h post-mortem, display only 65% of the uptake capacity of specimens collected and frozen within 7 h after death. Regional distribution of uptake sites and kinetic analysis in caudate tissue (Km = 1.1 μM; Vmax = 114pmoles/min/mg protein) are in agreement with data obtained in rat brain. The selectivity of the uptake process (non-glutamatergic drugs do not interfere at 1 mM) and the absolute and relative potencies of a spectrum of specific and metabolic uptake inhibitors are virtually identical in human caudate and rat striatum. Ultrastructural examination of P2 preparations from frozen human caudate tissue demonstrates the presence of synaptosomes (approximately 1/3 in density) identical to those observed in fresh rat striatum.

The findings support the view that glutamate uptake measurements in quick-frozen and thawed human brain samples

  • (1)

    are technically feasible and

  • (2)

    may provide a tool for the examination of glutamatergic mechanisms in normal and neuropathological states.

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