Unilateral up-regulation of glutamate receptors in limbic regions of amygdaloid-kindled rats

Abstract

Quantitative autoradiography was used to examine central binding sites for L-[3H]glutamate in amygdaloid-kindled rats since receptors for excitatory amino acids have been implicated in epileptiform activity and seizure behaviors. In tissue from rats killed five days after two kindled seizures, the ipsilateral hippocampus, entorhinal, perirhinal and parietal cortices had significantly (35-100%) greater densities of binding sites for L-[3H]glutamate than the opposite, contralateral side or operated, unstimulated controls. These regions receive excitatory inputs from the amygdala via the entorhinal cortex. Dissociation constants were not altered and significant differences were not observed in the binding parameters for L-[3H]glutamate between control and kindled rats or ipsilateral and contralateral sides of the amygdala, corpus striatum, nucleus accumbens or substantia nigra. The proportion and affinity of N-methyl-D-aspartate (NMDA)-sensitive binding sites for L-[3H]glutamate was unchanged after kindling, as were the relative proportions of kainate- and AMPA-(DL-alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid) sensitive sites. However, the density of NMDA and non-NMDA receptor subtypes was increased in the ipsilateral hippocampus, entorhinal, perirhinal and parietal cortices of kindled rats. These findings of specific, unilateral glutamate receptor up-regulation may indicate adaptive responses to the enhanced excitation found in kindling, and are consistent with other neuronal changes reported in early kindling.

Rat Hippocampal Kindling Induces Changes in the Glutamate Receptor mRNA Expression Patterns in Dentate Granule Neurons

“…The enhanced expression level of the AMPA-type GluR subunits suggests an increase in the number of the high affinity AMPA binding sites in the fascia dentata of kindled rats. However, autoradiographic studies of AMPA-selective binding sites in relation to kindling have provided conflicting results, reporting an increase (Cincotta et al, 1991), no change (Vezzani et al, 1990;Akiyama et al, 1992b), or a decrease (Okazaki et al, 1990) in the number of binding sites. The use of specific antibodies against the AMPA type GluR subunits in kindled animals may help to resolve this issue (Hampson et al, 1992;Petralia and Wenthold, 1992).…”

“…Presynaptic alterations in glutamatergic transmission may involve an increased glutamate exocytosis (Jarvie et al, 1990;Kamphuis et al, 1991b), while at the postsynaptic level kindling may be. related to an enhanced glutamate receptor sensitivity (Akiyama er al., 1992a;Cincotta et al, 1991). Accordingly, kindled animals show a hypersensitivity to epileptiform activity triggered by microinjection of L-glutamate in the amygdala (Croucher and Bradford, 1989;Mori et al, 1989).…”

Corneal kindled C57BL/6 mice exhibit saturated dentate gyrus long-term potentiation and associated memory deficits in the absence of overt neuron loss

“…For instance, trafficking of AMPA receptors to the postsynaptic membrane has long been appreciated as a prominent mechanism underlying LTP at excitatory synapses (Herring and Nicoll, 2016; Kessels and Malinow, 2009; Kneussel and Hausrat, 2016; Malenka, 2003; Malinow, 2003). Although not universally true, especially in some kindling models where AMPA receptor expression tends to not change or can even show decreased expression patterns, increased expression of AMPA receptors is also found in the hippocampus of a number of animal models of epilepsy and human TLE tissues (Behr et al, 2000; Cincotta et al, 1991; Ekonomou et al, 2001; Gitaí et al, 2010; Hosford et al, 1991; Lopes et al, 2013; Mathern et al, 1997; 1998; Schroeder et al, 1998). The data presented in this report suggests that corneal kindling of C57Bl/6 mice leads to an increased functional expression of AMPA receptors at the perforant path – DGC synapse; specifically, the strengthening of basal synaptic transmission and increased sEPSC amplitudes documented in Figures 6–7 and Table 1 are consistent with the increased expression, insertion, and/or phosphorylation of AMPA receptors on DGCs.…”

Anticonvulsant evaluation of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, in rodents

“…However, PTZ has been shown to interact with the GABA neurotransmitter and the GABA receptor complex (Löscher & Schmidt, 2006). On the other hand, investigations concerning the biochemistry of glutamate, especially modifications in glutamate binding after electrical kindling, showed increased glutamate release and increased receptor density in target neurons populations (Cincotta et al, 1991). Other studies provided evidence that AMPA and NMDA receptors are involved in the initiation of convulsions and their propagation, and that NMDA receptors antagonists retard the development of kindling (Becker et al, 2001).…”