Neuroprotective and long term potentiation improving effects of vitamin E in juvenile hypothyroid rats

Abstract. Protective effects of vitamin E (Vit E) on long term potentiation (LTP) impairment, neuronal apoptosis and increase of nitric oxide (NO) metabolites in the hippocampus of juvenile rats were examined. The rats were grouped (n=13) as: (1) control; (2) hypothyroid (Hypo) and (3) Hypo-Vit E. Propylthiouracil (PTU) was given in drinking water (0.05%) during 6 weeks. Vit E (20 mg/ kg) was daily injected (IP). To evaluate synaptic plasticity, LTP from the CA1 area of the hippocampus followed by high frequency stimulation to the ipsilateral Schafer collateral pathway was carried out. The cortical and hippocampal tissues were then removed to measure NO metabolites. The brains of 5 animals in each group were removed for apoptosis study. The hypothyroidism status decreased the slope, 10–90% slope and amplitude of field excitatory post synaptic potential (fEPSP) compared to the control group (P<0.01–P<0.001). Injection of Vit E increased the slope, 10–90% slope and amplitude of the fEPSP in the Hypo-Vit E group in comparison to the Hypo group (P<0.05–P<0.01). TUNEL positive neurons and NO metabolites were higher in the hippocampus of the Hypo rats, as compared to those in the hippocampus of the control ones (P<0.001). Treatment of the Hypo rats by Vit E decreased apoptotic neurons (P<0.01–P<0.001) and NO metabolites (P<0.001) in the hippocampus compared to the Hypo rats. The results of the present study showed that Vit E prevented the LTP impairment and neuronal apoptosis in the hippocampus of juvenile hypothyroid rats.

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Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models

Acta Neuropathologica Communications ◽

10.1186/s40478-019-0813-4 ◽

2019 ◽

Vol 7 (1) ◽

Author(s):

Enrico Faldini ◽

Tariq Ahmed ◽

Luc Bueé ◽

David Blum ◽

Detlef Balschun

Keyword(s):

Synaptic Plasticity ◽

Transgenic Mice ◽

Mouse Models ◽

Long Term Potentiation ◽

High Frequency Stimulation ◽

Synaptic Loss ◽

Ca1 Region ◽

Term Potentiation ◽

Frequency Stimulation

AbstractMany mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

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Cholecystokinin release triggered by NMDA receptors produces LTP and sound–sound associative memory

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816833116 ◽

2019 ◽

Vol 116 (13) ◽

pp. 6397-6406 ◽

Cited By ~ 3

Author(s):

Xi Chen ◽

Xiao Li ◽

Yin Ting Wong ◽

Xuejiao Zheng ◽

Haitao Wang ◽

...

Keyword(s):

Associative Learning ◽

Associative Memory ◽

High Frequency ◽

Low Frequency ◽

Long Term Potentiation ◽

High Frequency Stimulation ◽

Low Frequency Stimulation ◽

Term Potentiation ◽

Frequency Stimulation

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK−/−mice lacked neocortical LTP and showed deficits in a cue–cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue–cue associative memory.

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LTD and LTP at the Developing Retinogeniculate Synapse

Journal of Neurophysiology ◽

10.1152/jn.90618.2008 ◽

2009 ◽

Vol 102 (6) ◽

pp. 3082-3090 ◽

Cited By ~ 17

Author(s):

Jokūbas Žiburkus ◽

Emily K. Dilger ◽

Fu-Sun Lo ◽

William Guido

Keyword(s):

Optic Tract ◽

Long Term Potentiation ◽

Dorsal Lateral Geniculate Nucleus ◽

High Frequency Stimulation ◽

Retinal Stimulation ◽

Term Potentiation ◽

Frequency Stimulation ◽

Retinogeniculate Synapse

The purpose of the present study was to determine whether retinal activity can support long-term changes in synaptic strength in the developing dorsal lateral geniculate nucleus (LGN) of thalamus. To test for this we made use of a rodent in vitro explant preparation in which retinal afferents and the intrinsic circuitry of the LGN remain intact. We repetitively stimulated the optic tract with a tetanus protocol that approximated the temporal features of spontaneous retinal waves. We found the amplitude of extracellular field potentials evoked by retinal stimulation changed significantly after tetanus and that the polarity of these alterations was related to postnatal age. At a time when substantial pruning of retinal connections occurs (postnatal day 1 [P1] to P14), high-frequency stimulation led to an immediate and long-term depression (LTD). However, at times when pruning wanes and adultlike patterns of connectivity are stabilizing (P16 to P30), the identical form of stimulation produced a modest form of potentiation (long-term potentiation [LTP]). The LTD was unaffected by the bath application of γ-aminobutyric acid type A and N-methyl-d-aspartate receptor antagonists. However, both LTD and LTP were blocked by L-type Ca2+-channel antagonists. Thus the Ca2+ influx associated with L-type channel activation mediates the induction of synaptic plasticity and may signal the pruning and subsequent stabilization of developing retinogeniculate connections.

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