Acute and chronic changes in glycogen phosphorylase in hippocampus and entorhinal cortex after status epilepticus in the adult male rat

Abstract

Glial cells provide energy substrates to neurons, in part from glycogen metabolism, which is influenced by glycogen phosphorylase (GP). To gain insight into the potential subfield and laminarspecific expression of GP, histochemistry can be used to evaluate active GP (GPa) or totalGP (GPa + GPb). Using this approach, we tested the hypothesis that changes in GP would occur under pathological conditions that are associated with increased energy demand, i.e. severe seizures (status epilepticus or 'status'). We also hypothesized that GP histochemistry would provide insight into changes in the days and weeks after status, particularly in the hippocampus and entorhinal cortex, where there are robust changes in structure and function. One hour after the onset of pilocarpineinduced status, GPa staining was reduced in most regions of the hippocampus and entorhinal cortex relative to saline-injected controls. One week after status, there was increased GPa and totalGP, especially in the inner molecular layer, where synaptic reorganization of granule cell mossy fibre axons occurs (mossy fibre sprouting). In addition, patches of dense GP reactivity were evident in many areas. One month after status, levels of GPa and totalGP remained elevated in some areas, suggesting an ongoing role of GP or other aspects of glycogen metabolism, possibly due to the evolution of intermittent, recurrent seizures at approximately 3-4 weeks after status. Taken together, the results suggest that GP is dynamically regulated during and after status in the adult rat, and may have an important role in the pilocarpine model of epilepsy.

Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

“…On this basis, a possible causal link between glycogen metabolism and epileptogenesis has been proposed (Cloix and Hevor, 2011). However, studies aimed at establishing such a role for glycogen failed to demonstrate consistent effects of seizures on glycogen levels (see Walling et al, 2007). The lack of success in correlating epilepsy and glycogen content has been evidenced by the finding that some animals subjected to MSO developed violent seizures without any variation in tissue glycogen (Bernard-Helary et al, 2000).…”

Brain glycogen content is increased in the acute and interictal chronic stages of the mouse pilocarpine model of epilepsy

“…Similarly, brain and muscle glycogen phosphorylase mRNA levels were unchanged in hippocampal formations from chronic CSE mice. We note that in the rat pilocarpine model, glycogen phosphorylase activity was increased one month after SE in CA1 and CA3 pyramidal layers of the hippocampus 42 …”

Ischemic–hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus

“…Using also an antibody against the cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) [27,28], we differently illustrated the same, already described changes of distribution of astrocyte immunostaining in the core lesion and its surroundings. In addition, damage to hippocampal astrocytes was also shown, but not detailed, by another independent study based on glycogen phosphorylase enzymohistochemistry, in which a complete loss of this enzymatic activity was evident in the strata lacunosummoleculare and radiatum of the CA3b sector, one week after SE induction [29]. Interestingly, an initial loss of glycogen phosphorylase activity was present also in slices obtained just after 1 h of SE [29], and consistently, this lesion appeared very close to the dentate gyrus upper blade, exactly where we found damage to blood vessels [17].…”