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1 |
Short-term neuronal effects of Fumonisin B1 on neuronal activity in rodents
اثرات عصبی کوتاه مدت Fumonisin B1 بر فعالیت عصبی در جوندگان-2020 Fumonisin B1 (FB1) is a mycotoxin produced by microscopic fungi (mostly Fusarium
species), which may infect our major crops. The toxin inhibits the development of these plants
and may also have harmful effects on animals and humans consuming the infected crops.
FB1 inhibits sphingolipid biosynthesis which leads to altered membrane characteristics and
consequently, altered cellular functions. There are some indications that the toxin has
inhibitory effects on neuronal activity in case of repeated consumption, presumably due to
sphingolipid depletion. However, according to new literature data, FB1 may have acute
excitatory neural effects, too, via different mechanisms of action. Therefore, in the present
study, we addressed the neuronal network effects of FB1 following acute treatment, using
different electrophysiological techniques in vitro and in vivo.
Acute treatments with FB1 (10-100 μM) were carried out on brain slices, tissue cultures and
live animals. After direct treatment of samples, electrically evoked or spontaneous field
potentials were examined in the hippocampus and the neocortex of rat brain slices and in
hippocampal cell cultures. In the hippocampus, a short-term increase in the excitability of
neuronal networks and individual cells was observed in response to FB1 treatment. In some
cases, the initially enhanced excitation was reversed presumably due to overactivation of
neuronal networks. Normal spontaneous activity was found to be stimulated in hippocampal
cell cultures. Seizure susceptibility was not affected in the neocortex of brain slices.
For the verification of the results caused by direct treatment, effects of systemic
administration of FB1 (7.5 mg/kg, i.p.) were also examined. Evoked field potentials recorded
in vivo from the somatosensory cortex and cell activation measured by the c-fos technique in hippocampus and somatosensory cortex were analyzed. However, the hippocampal and cortical stimulatory effect detected in vitro could not be demonstrated by these in vivo assays.
Altogether, the toxin enhanced the basic excitability of neurons and neuronal networks after
direct treatment but there were no effects on the given brain areas after systemic treatment in
vivo. Based on the observed in vitro FB1 effects and the lack of data on the penetration of
FB1 across the blood-brain barrier, we assume that in vivo consequences of FB1
administration can be more prominent in case of perturbed blood-brain barrier functions. Keywords: neurotoxicity | electrophysiology | c-Fos, mycotoxin | field potential | brain slice | tissue culture |
مقاله انگلیسی |
2 |
Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks
انعطاف پذیری انتقال سیناپسی در شبکه های عصبی مشتق از سلولهای بنیادی انسان-2020 Long-term potentiation and depression, inferred from analysis on brain slices, are considered the
cellular processes underlying learning and memory formation. They have not so far been demonstrated
in human stem cell-derived neurons. By expressing channelrhodopsin in hESCs-derived glutamate
neurons and co-culturing them with GABA neurons, we found that blue light stimulation
increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) and decreased the
ratio of paired pulse facilitation (PPF) in non-ChR2-expressing GABA neurons, indicating a facilitating
action at the presynaptic terminals. When paired with postsynaptic depolarization, the repetitive
stimulation significantly increased the amplitude of light-evoked EPSCs that persisted during the
period, indicating long-term potentiation (LTP). In contrast, low-frequency light stimulation induced
long-term depression (LTD). These effects were blocked by N-methyl-D-aspartic acid (NMDA) receptor
antagonists, suggesting NMDA receptor-mediated synaptic plasticity in human neural networks.
Furthermore, induced pluripotent stem cell (iPSC)-derived neurons of patient with Down syndrome
showed absence of LTP or LTD. Thus, our platformoffers a versatile model for assessing human neural
plasticity under physiological and pathological conditions |
مقاله انگلیسی |