Differential Impairments of Spatial Memory and Social Behavior in Two Models of Limbic Epilepsy

Abstract

To explore memory impairments in temporal lobe epilepsy, we used two experimental models in the rats: (a) kainate-induced status epilepticus (SE) resulting in excitotoxic damage and in later spontaneous seizures; and (b) amygdala kindling, known to induce no lesions (or only minor) and neuronal reorganization. Long-term effects of these models on memory were investigated with a spatial learning task in a radial-arm maze, and a social interaction test that implies degree of short-term memory. An histological analysis was made to determine neuronal damage or loss caused by epileptic activity in brain regions that could be related to memory functions. Kainate-induced epilepsy produced large memory deficits in animals tested 5 months after the injection. The rats showed severe lesions in amygdala and hippocampus and piriform and entorhinal cortex. Spatial memory was strongly diminished. The social memory test was severely impaired, probably due to the extent of amygdala injury, which is known to disturb social behavior. On the contrary, kindled rats showed no evident lesion in any brain region and displayed performances as good as those of controls in both tests. These experiments demonstrated that memory deficits appear to be related to the severity of neuronal damage in limbic areas, and the ability to develop seizures (permanence) is not solely responsible for these memory disturbances.

Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

“…Li-Pilo SE is known to impair spatial memory (Detour et al, 2005). Spatial memory was also diminished in KA or pentylenetetrazole-induced SE models (Letty et al, 1995;Mortazavi et al, 2005). Our SE group was severely impaired in the spatial learning task, as shown by the time to reach learning criterion and number of memory errors.…”

Decreased neuronal differentiation of newly generated cells underlies reduced hippocampal neurogenesis in chronic temporal lobe epilepsy

“…The early phase after the initial precipitating injury (IPI) such as status epilepticus (SE) or hippocampal injury is characterized by an increased DG neurogenesis and abnormal migration of a substantial fraction of newly generated granule cells into the dentate hilus (Gray and Sundstrom, 1998; Parent et al, 1997, 2006; Scharfman et al, 2000, 2002, 2003; Gong et al, 2007; Scharfman and Gray, 2007; Kuruba et al, 2009). In contrast, the chronic phase of TLE exhibits substantially declined DG neurogenesis (Hattiangady et al, 2004; Hattiangady and Shetty, 2008a), and is associated with spontaneous recurrent motor seizures (SRMS), learning and memory impairments and depression (Letty et al, 1995; Schwarcz and Witter, 2002; Rao et al, 2006a, 2007). Because of the perceived functions of DG neurogenesis concerning learning, memory and mood (Shors et al, 2001; van Praag et al, 2002; Drapeau et al, 2003; Santarelli et al, 2003; Aimone et al, 2006; Sahay and Hen, 2007; Dupret et al, 2008; Imayoshi et al, 2008), it is plausible that decreased DG neurogenesis during chronic epilepsy contributes to impairments in these functions.…”

Carbamazepine Enhances Discriminative Memory in a Rat Model of Epilepsy

“…In preclinical studies, spatial memory of temporal lobe epileptic rats is shown to be compromised (5,6). Light-discrimination tasks and Y-maze performance also are impaired in epileptic animals, and CBZ reverses these difficulties (7,8).…”