Neuraminidase inhibition primes short-term depression and suppresses long-term potentiation of synaptic transmission in the rat hippocampus.

Neuraminidase (NEU) is a key enzyme that cleaves negatively charged sialic acid residues from membrane proteins and lipids. Clinical and basic science studies have shown that an imbalance in NEU metabolism or changes in NEU activity due to various pathological conditions parallel with behavior and cognitive impairment. It has been suggested that the decreases of NEU activity could cause serious neurological consequences. However, there is a lack of direct evidences that modulation of endogenous NEU activity can impair neuronal function. Using combined rat entorhinal cortex/hippocampal slices and a specific inhibitor of NEU, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NADNA), we examined the effect of downregulation of NEU activity on different forms of synaptic plasticity in the hippocampal CA3-to-CA1 network. We show that NEU inhibition results in a significant decrease in long-term potentiation (LTP) and an increase in short-term depression. Synaptic depotentiation restores LTP in NADNA-pretreated slices to the control level. These data suggest that short-term NEU inhibition produces the LTP-like effect on neuronal network, which results in damping of further LTP induction. Our findings demonstrate that downregulation of NEU activity could have a major impact on synaptic plasticity and provide a new insight into the cellular mechanism underlying behavioral and cognitive impairment associated with abnormal metabolism of NEU.

Status epilepticus results in region-specific alterations in seizure susceptibility along the hippocampal longitudinal axis.

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome in adults. In particular, the hippocampus is highly susceptible to abnormal synchronization. Recent advances in the surgical treatment of patients with refractory TLE have shown that multiple hippocampal transections can effectively control seizures. It has been suggested that in TLE the synchrony in the longitudinal connections is required for seizure generation; however the physiological background for the increase in hippocampal synchronization along the longitudinal axis is not fully understood. The hippocampus varies in seizure susceptibility along its longitudinal axis with the ventral hippocampus (VH) region being more seizure-prone and susceptible to neuronal damage than the dorsal hippocampus (DH). In the present study we studied seizure susceptibility along the longitudinal axis of the hippocampus following pilocarpine-induced status epilepticus (SE). In control conditions the VH generates epileptiform activity (EA) more frequently than the DH when exposed to a low Mg(2+)/1Ca(2+)/5K(+) solution. Following SE the probability of inducing epileptiform activity (EA) is similar in the VH and DH slices. This SE-induced change is due to an increase in the proportion of DH slices responding to the low Mg(2+)/1Ca(2+)/5K(+) solution with EA. Moreover, both the VH and DH show similar responses to a low Mg(2+)/1Ca(2+)/5K(+) solution. These findings indicate that the hippocampus undergoes significant functional changes following SE, which may provide the necessary increase of synchrony along the longitudinal axis to generate seizures in TLE.