The development of changes in hippocampal GABA immunoreactivity in the rat kindling model of epilepsy: A light microscopic study with gaba antibodies

Abstract

Immunocytochemical techniques were used to study changes of GABA immunoreactivity in the rat hippocampal CA1 region during kindling epileptogenesis, gradually developing over a period of two weeks by daily electrical tetanization of Schaffer collaterals/commissural fibres. The number of GABA-immunoreactive somata per mm2 was quantified in CA1 region after 6 and 14 stimulus-induced afterdischarges and in fully kindled animals. The absolute values were compared with those obtained from controls and the relative difference between the side where the stimulations were applied and the contralateral side was determined. In comparison to controls the rats showed, after 6 afterdischarges at the ipsilateral, stimulated side, a slight increase in cell density of about 10%; after 14 afterdischarges, there was a significant increase of 38% together with an enhanced labelling density, while in fully kindled rats (34 afterdischarges) there was no significant difference with controls. At the contralateral side, we observed a different pattern of, respectively, a small decrease (17%), no significant difference, and a significant increase of 22% in fully kindled animals. This result is discussed in relation to observations that fully kindled rats, investigated 24 days after the last seizure of the acquisition phase, showed rather a significant decrease by 35% of cell density at the stimulated side and a regional loss of immunoreactivity of varicosities. At this point in time, no significant changes were found at the contralateral side. The complex time-course of GABA immunoreactivity during epileptogenesis consists of a transient increase in the early phase of kindling acquisition followed by a process of gradual reduction that leads to the long-term decrease of GABA immunoreactivity and high excitability.

Increased expression of gamma-aminobutyric acid transporter-1 in the forebrain of infant rats with corticotropin-releasing hormone-induced seizures but not in those with hyperthermia-induced seizures

“…Many previous neurophysiological studies have indicated that a failure of inhibition is a principal reason for neuronal hyperexcitability during epileptic seizures (Gean et al, 1989;Kamphuis et al, 1987;Kapur et al, 1989;Morimoto et al, 1987a,b;Ribak, 1991). Gammaaminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system.…”

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“…This induces a progressive and permanent decrease in seizure threshold, which usually is apparent as increasing intensities of convulsive responses to successive, initially subconvulsive, stimuli (Goddard et al 1969). There has been disagreement on what happens to inhibition with kindling, but a combination of recent anatomical and physiological studies suggests that after an initial transient increase, GABA-mediated inhibition progressively weakens as the kindling develops (Morimoto & Goddard, 1986; Kamphuis, Wadman, Buijs & Lopes da Silva, 1987;Maru & Goddard, 1987 a; Kamphuis, Lopes da Silva & Wadman, 1988), perhaps as a result of plastic changes involving NMDA receptors (Stelzer, Slater & Ten Bruggencate, 1987).…”

Activation of Kainate GLUK5 Transmission Rescues Kindling-Induced Impairment of LTP in the Rat Lateral Amygdala

“…g-Aminobutyric acid (GABA)ergic transmission may also be important in TLE, as GABAergic interneurons seem to be involved in kindling-induced plasticity changes in the amygdala (Kamphuis et al, 1987;Callahan et al, 1991) and activation of kainate receptors modulates GABAergic synaptic transmission in the amygdala (Braga et al, 2003). Therefore, the aim of this study was to investigate whether the activation of GLU K5 kainate receptors and/or inactivation of GABA A receptors can rescue the kindling-induced impairment of LA-LTP.…”