Neuraminidase Inhibition Primes Short-Term Depression and Suppresses Long-Term Potentiation of Synaptic Transmission in the Rat Hippocampus

Abstract

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.

Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory

“…The mutant mice lacking ST8SiaIV, a sialyltransferase for PSA production, exhibit abnormal LTP at Schaffer collateral-CA1 synapses [36]. Since inhibition of sialidase impairs LTP at Schaffer collateral-CA1 synapses, regulation of sialyl signaling by sialidase is necessary for memory processing in the CA1 region [37]. …”

The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment

“…Within the SARS-CoV-2 context, chloroquine is also known to cause similar CNS-related adverse effects [ 240 ]. Although the exact mechanisms involved in these CNS adverse effects are unknown, it may include altered neuroplasticity [ 255 ], via direct (programmed necrosis, cell lysis and/or by inducing apoptosis and necroptosis [ [256] , [257] , [258] ]) or indirect mechanisms [ 258 ], such as the activation of toll-like receptor signalling receptors (TLRs) 3, 7, and 8. The latter leads to increased free radical production and inflammation and ultimately neuronal damage.…”

The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

“…Hippocampal-dependent spatial memory in rats assessed in the Morris water maze is attenuated by administration of DANA or Neu4 siRNA into the hippocampus [ 12 ]. DANA also attenuates the LTP at synapses between the hippocampal mossy fibers and CA3 pyramidal cells, and between Schaffer collaterals and CA1 pyramidal cells [ 12 , 16 ]. Contextual learning with fear conditioning increased the amount of sialic acid released into the hippocampal extracellular fluid ( Figure 2 C).…”