Adult Genetic Absence Epilepsy Rats From Strasbourg Research Articles

Astrocytes may play a role in the etiology of absence epilepsy: A comparison between immature GAERS not yet expressing seizures and adults

Neuronal-astrocytic interactions in 1-month-old Genetic Absence Epilepsy Rats from Strasbourg (GAERS) before the occurrence of seizures are compared to those in non-epileptic rats (NERs) and in adult GAERS expressing epilepsy. Animals received [1-13C]glucose and [1,2-13C]acetate, preferential substrates of neurons and astrocytes, respectively, and extracts from cerebral cortex, subcortex and cerebellum were analyzed by NMR spectroscopy. Increased mitochondrial metabolism took place in the cortical neurons of immature and adult GAERS and therefore does not seem to be a consequence of the occurrence of absence seizures. Glutamine supply to GABAergic neurons was reduced in cortex and subcortex in young GAERS, as reflected by increased glutamine content and decreased 13C-labeling of GABA. In the brain of immature GAERS, interactions between glutamatergic neurons and astrocytes appeared normal whereas increased astrocytic metabolism took place in adult GAERS, suggesting that astrocytic alterations could possibly be the cause of seizures.

Specific alteration in the expression of glial fibrillary acidic protein, glutamate dehydrogenase, and glutamine synthetase in rats with genetic absence epilepsy.

Astrocytes play a predominant role in energy metabolism and in the catabolism of gamma-aminobutyric acid (GABA) and glutamate, neurotransmitters critically involved in epileptic processes. We show specific astrocytic alterations in the genetic absence epilepsy rats from Strasbourg (GAERS). Spontaneous absence seizures appear in this strain in the cortex and thalamus after the age of 1 month. In these brain structures, we demonstrate increased GFAP expression in both adult and young GAERS, suggesting that reactive astrocytes are already present before the onset of seizures. Glutamate dehydrogenase (GDH) and glutamine synthetase (GS), which are localized mainly in astrocytes and involved in glutamate catabolism, are shown to be differentially altered. GDH expression was increased in the thalamus of both young and adult GAERS and in the cortex of young GAERS. GS expression was slightly decreased in the thalamus of young GAERS. These astrocytic modifications are not adaptive responses to seizures, as the modifications appear before the development of absence seizures. Thus, astrocytes might be involved in the neuronal processes giving rise to epileptic seizures in this strain.

Specific alteration in the expression of glial fibrillary acidic protein, glutamate dehydrogenase, and glutamine synthetase in rats with genetic absence epilepsy

Astrocytes play a predominant role in energy metabolism and in the catabolism of gamma-aminobutyric acid (GABA) and glutamate, neurotransmitters critically involved in epileptic processes. We show specific astrocytic alterations in the genetic absence epilepsy rats from Strasbourg (GAERS). Spontaneous absence seizures appear in this strain in the cortex and thalamus after the age of 1 month. In these brain structures, we demonstrate increased GFAP expression in both adult and young GAERS, suggesting that reactive astrocytes are already present before the onset of seizures. Glutamate dehydrogenase (GDH) and glutamine synthetase (GS), which are localized mainly in astrocytes and involved in glutamate catabolism, are shown to be differentially altered. GDH expression was increased in the thalamus of both young and adult GAERS and in the cortex of young GAERS. GS expression was slightly decreased in the thalamus of young GAERS. These astrocytic modifications are not adaptive responses to seizures, as the modifications appear before the development of absence seizures. Thus, astrocytes might be involved in the neuronal processes giving rise to epileptic seizures in this strain.

Metabolic activity is increased in discrete brain regions before the occurrence of spike-and-wave discharges in weanling rats with genetic absence epilepsy

In the present study, we measured basal local cerebral metabolic rates for glucose (LCMRglcs) in immature genetic absence epilepsy rats from Strasbourg (GAERS) at postnatal day 21 (P21), at which age no spike-and-wave discharges can be recorded. LCMRglcs in GAERS were compared to those in control non-epileptic (NE) rats of the same age selected from our breeding colony. LCMRglcs were measured in 60 structures by the quantitative [ 14C]2-deoxyglucose (2DG) autoradiographic technique. In P21 GAERS, LCMRglcs were similar to those of P21 NE rats in 46 areas. They increased over NE control levels in two groups of structures. First, metabolic increases were recorded in limbic structures such as entorhinal and piriform cortex, lateral septum as well as all hippocampal subfields and basolateral amygdala, although no spike-and-wave discharges can be recorded from those areas in adult GAERS. On the other hand, increases in LCMRglcs were also recorded in substantia nigra pars reticulata, superior colliculus and globus pallidus which are structures involved in the control of seizure activity. Finally, significant metabolic decreases in P21 GAERS were recorded in two posterior auditory regions, the inferior colliculus and the superior olive. In conclusion, our data show that the genetic mutation(s) underlying the cellular and molecular events responsible for the expression of spike-and-wave discharges in adult GAERS is(are) able to increase metabolic activity in limbic structures and in the nigral inhibitory system before the occurrence of absence seizures. Conversely, the full electrocortical maturation seems necessary for the expression of spike-and-wave discharges with the concurrent increase in LCMRglcs in adult GAERS.