The effects of hyperbilirubinaemia on synaptic plasticity in the dentate gyrus region of the rat hippocampus in vivo

Abstract

Introduction: The aim of our study is to investigate the effect of hyperbilirubinaemia on synaptic plasticity in the dentate gyrus (DG) region of the rat hippocampus. Material and methods: Seven-day-old healthy Sprague Dawley (SD) rats were randomly divided into a control group and an experiment group (n = 20 in each group). The input/output (I/O) functions, paired-pulse reactions (PPR), excitatory postsynaptic potential (EPSP), and population spike (PS) amplitude were measured in the DG area of both groups of rats in response to stimulation applied to the lateral perforant path. Results: Compared with that in the control rats, the current-voltage curves of both EPSP slope and PS amplitude in the experimental rats were significantly depressed. The average peak facilitation was 187 ±16% in the control and 164 ±18% in the experiment group (F = 21.054, p < 0.01). The facilitation period duration of PS was 155 ms in the experimental rats, which was less than that of the controls (235 ms). In the control group, the long-term potentiation (LTP) amplitudes were 140 ±3.5% and 242 ±6%, when estimated from the EPSP slope and PS amplitude, respectively, which were significantly depressed to 124 ±3.4% (EPSP slope, F = 70.489, p < 0.01) and 138 ±8.6% (PS amplitude, F = 253.46, p < 0.01), respectively, in the experiment group. Conclusions: These findings suggest that hyperbilirubinaemia could induce impairment of synaptic plasticity in the rat DG area in vivo, including I/O function, paired-pulse ratio (PPR), and LTP, which may be closely related to cognitive impairment.

Comparing prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 diabetes mellitus

“…It is well accepted that memory is intimately associated with the plasticity of neuronal synapses in the hippocampus [ 66 ]. In our study, the granular cells of the dentate gyrus region were significantly fewer in diabetic, exercised, and metformin-treated groups compared to the control group.…”

Effects of bilirubin on the development and electrical activity of neural circuits

“… Chang et al (2009) reported that long-term potentiation (LTP) and long-term depression (LTD) induction were impaired by UCB (1–10 μM for 24–48 h) in a time- and concentration-dependent manner ( Chang et al, 2009 ), possibly through calpain-mediated proteolytic cleavage of NMDA receptor subunits. In vivo studies have also demonstrated that hyperbilirubinemia can cause LTP inhibition ( Zhang et al, 2003 ; Yang et al, 2020 ) and the impairment of input/output functions and paired-pulse reactions, which reflect the basal synaptic response and short-term synaptic plasticity ( Yang et al, 2020 ).…”

The possible effect of coenzyme Q10 and captopril on acetaminophen-induced encephalopathy in rats: possible influence on autophagy, antioxidant and Na+/K+ ATPase

“…It is well known that a high level of ammonia is toxic to the ner-vous system; it results in encephalopathy, and eventually coma and death [39]. Moreover, the hyperbilirubinemia that may be encountered in patients with hepatic encephalopathy induced impairment of memory through impairing synaptic plasticity in the hippocampus via disturbing longterm potentiation that facilitates information storage at the synaptic level and is considered the chief component of memory consolidation [40]. Acetaminophen can easily penetrate the blood brain barrier, activating the neuronal cytochrome P450 2E1, generating toxic metabolites such as N-acetyl-p-benzoquinoneimine (NAPQI), which decreases glutathione, ascorbic acid, superoxide dismutase levels, resulting in oxidative stress and neurotoxicity [3].…”