Preserved induction of long-term potentiation in the stratum radiatum in the CA1 field of hippocampal slices from transgenic mice overexpressing ornithine decarboxylase and overproducing putrescine

Abstract

The role of putrescine in synaptic neurotransmission and plasticity was studied using transgenic mice overexpressing ornithine decarboxylase (ODC), a polyamine-synthesizing enzyme. Transgenic mice were produced using the standard microinjection technique leading to elevated levels of putrescine in the periphery and in the brain. The experiments investigated whether or not ODC mice with elevated levels of putrescine show alterations in synaptic transmission and induction of long-term potentiation in the CA1 field of the hippocampus in vitro. Our results indicated that (1) putrescine levels in brain slices of the transgenic mice were more than ten times higher than those in fresh slices of control mice, although the absolute levels of putrescine and spermine decreased (by 15 and 40%, respectively) after 3-6 h incubation in vitro, while the levels of spermidine slightly increased (by 10%), (2) the excitatory synaptic response waveforms were wider (an increased half-width), and paired-pulse facilitation was somewhat reduced in ODC mice as compared to controls, and (3) potentiation of excitatory synaptic responses (measured 30-45 min after theta burst stimulation) did not differ between ODC and control mice. These results indicate that synaptic transmission is affected, but synaptic plasticity in the field CA1 assessed in vitro is not changed by elevated levels of intracellular putrescine.

Neuroprotective role of ornithine decarboxylase activation in transient focal cerebral ischaemia: a study using ornithine decarboxylase-overexpressing transgenic rats

“…1998). These observations are related to high hippocampal putrescine and are thought to reflect effects on transmitter release and/or inhibition of postsynaptic receptors/ion channels (Pussinen et al . 1998).…”

“…Although much work is required to demonstrate the site of action of putrescine, it is tempting to speculate that extensively increased levels of the diamine influence neuronal excitability, thereby exerting neuroprotection. Recent results from electrophysiology in vitro show that excitatory synaptic response waves are wider and paired-pulse facilitation is impaired in hippocampal brain slices from ODCoverexpressing transgenic animals (Pussinen et al, 1998). These observations are related to high hippocampal putrescine and are thought to reflect effects on transmitter release and/or inhibition of postsynaptic receptors/ion channels (Pussinen et al, 1998).…”

“…Recent results from electrophysiology in vitro show that excitatory synaptic response waves are wider and paired-pulse facilitation is impaired in hippocampal brain slices from ODCoverexpressing transgenic animals (Pussinen et al, 1998). These observations are related to high hippocampal putrescine and are thought to reflect effects on transmitter release and/or inhibition of postsynaptic receptors/ion channels (Pussinen et al, 1998). This hypothesis is particularly appealing, as ODC transgenic animals exhibit elevated seizure threshold and learning defect, possibly as a consequence of weakened NMDA receptor function (Halonen et al, 1993).…”

“…1993) characteristics involving employment of hippocampal structures and NMDA receptors. Direct electrophysiological evaluation of hippocampal brain slices in vitro has shown that evoked field excitatory postsynaptic potentials are wider and paired‐pulse facilitation reduced in amplitude in ODC transgenic animals (Pussinen et al . 1998).…”

“…In addition, the transgenic animals show impaired spatial learning and memory (Halonen et al, 1993) characteristics involving employment of hippocampal structures and NMDA receptors. Direct electrophysiological evaluation of hippocampal brain slices in vitro has shown that evoked field excitatory postsynaptic potentials are wider and paired-pulse facilitation reduced in amplitude in ODC transgenic animals (Pussinen et al, 1998). Thus there is substantial evidence to show that polyamine profile due to ODC overexpression may influence electrical function through effect(s) on ion channels and/or neurotransmission.…”