Effects of the neurotrophic agent T-817MA on oligomeric amyloid-β–induced deficits in long-term potentiation in the hippocampal CA1 subfield

CNG channels are cyclic nucleotide-gated Ca2+-permeable channels that are suggested to be involved in the activity-dependent alterations of synaptic strength that are thought to underlie information storage in the CNS. In this study, we isolated an endogenous RNA transcript antisense to CNGα1 mRNA. This transcript was capable of down-regulating the expression of sense CNGα1 in theXenopus oocyte expression system. RT-PCR, Northern blot, and in situ hybridization analyses showed that the transcript was coexpressed with CNGα1 mRNA in many regions of human brain, notably in those regions that were involved in long-term potentiation and long-term depression, such as hippocampal CA1 and CA3, dentate gyrus, and cerebellar Purkinje layer. Comparison of expression patterns between adult and fetal cerebral cortex revealed that there were concurrent developmental changes in the expression levels of anti-CNG1 and CNGα1. Treatment of human glioma cell T98 with thyroid hormone T3 caused a significant increase in anti-CNG1 expression and a parallel decrease in sense CNGα1 expression. These data suggest that the suppression of CNGα1 expression by anti-CNG1 may play an important role in neuronal functions, especially in synaptic plasticity and cortical development. Endogenous antisense RNA-mediated regulation may represent a new mechanism through which the activity of ion channels can be regulated in the human CNS.

Download Full-text

PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

Nature Communications ◽

10.1038/s41467-020-20523-3 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Pojeong Park ◽

John Georgiou ◽

Thomas M. Sanderson ◽

Kwang-Hee Ko ◽

Heather Kang ◽

...

Keyword(s):

Ampa Receptors ◽

Single Channel ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Theta Burst Stimulation ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Necessary And Sufficient ◽

Theta Burst

AbstractLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

Download Full-text

Phosphatidylinositol 3-Kinase Is Required for the Expression But Not for the Induction or the Maintenance of Long-Term Potentiation in the Hippocampal CA1 Region

Journal of Neuroscience ◽

10.1523/jneurosci.22-09-03359.2002 ◽

2002 ◽

Vol 22 (9) ◽

pp. 3359-3365 ◽

Cited By ~ 157

Author(s):

Pietro Paolo Sanna ◽

Maurizio Cammalleri ◽

Fulvia Berton ◽

Cindy Simpson ◽

Robert Lutjens ◽

...

Keyword(s):

Long Term Potentiation ◽

Phosphatidylinositol 3 Kinase ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Phosphatidylinositol 3

Download Full-text

Neuroprotective properties of mitochondria-targeted antioxidants of the SkQ-type

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0036 ◽

2016 ◽

Vol 27 (8) ◽

pp. 849-855 ◽

Cited By ~ 17

Author(s):

Nickolay K. Isaev ◽

Elena V. Stelmashook ◽

Elisaveta E. Genrikhs ◽

Galina A. Korshunova ◽

Natalya V. Sumbatyan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Area ◽

Hippocampal Slices ◽

Amyloid Β ◽

Long Term Potentiation ◽

Term Potentiation ◽

Neuroprotective Action

AbstractIn 2008, using a model of compression brain ischemia, we presented the first evidence that mitochondria-targeted antioxidants of the SkQ family, i.e. SkQR1 [10-(6′-plastoquinonyl)decylrhodamine], have a neuroprotective action. It was shown that intraperitoneal injections of SkQR1 (0.5–1 μmol/kg) 1 day before ischemia significantly decreased the damaged brain area. Later, we studied in more detail the anti-ischemic action of this antioxidant in a model of experimental focal ischemia provoked by unilateral intravascular occlusion of the middle cerebral artery. The neuroprotective action of SkQ family compounds (SkQR1, SkQ1, SkQTR1, SkQT1) was manifested through the decrease in trauma-induced neurological deficit in animals and prevention of amyloid-β-induced impairment of long-term potentiation in rat hippocampal slices. At present, most neurophysiologists suppose that long-term potentiation underlies cellular mechanisms of memory and learning. They consider inhibition of this process by amyloid-β1-42as anin vitromodel of memory disturbance in Alzheimer’s disease. Further development of the above studies revealed that mitochondria-targeted antioxidants could retard accumulation of hyperphosphorylated τ-protein, as well as amyloid-β1-42, and its precursor APP in the brain, which are involved in developing neurodegenerative processes in Alzheimer’s disease.

Download Full-text

AMPA Silencing Is a Prerequisite for Developmental Long-Term Potentiation in the Hippocampal CA1 Region

Journal of Neurophysiology ◽

10.1152/jn.90476.2008 ◽

2008 ◽

Vol 100 (5) ◽

pp. 2605-2614 ◽

Cited By ~ 23

Author(s):

Therése Abrahamsson ◽

Bengt Gustafsson ◽

Eric Hanse

Keyword(s):

Developmental Stages ◽

Long Term Potentiation ◽

Synaptic Strength ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Silent Synapses ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Hippocampal Ca3

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) unsilencing is an often proposed expression mechanism both for developmental long-term potentiation (LTP), involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3–CA1 connection naïve (nonstimulated) synapses are AMPA signaling and AMPA-silent synapses are created from naïve AMPA-signaling (AMPA-labile) synapses by test-pulse synaptic activation (AMPA silencing). To investigate to what extent LTPs at different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naïve synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naïve synaptic strength. Thus this early, or developmental, LTP is nothing more than an unsilencing (dedepression) and stabilization of the AMPA signaling that was lost by the prior AMPA silencing. This dedepression and stabilization of AMPA signaling was mimicked by the presence of the protein kinase A activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a “genuine” potentiation (as opposed to a dedepression) not explained by unsilencing and stabilization of AMPA-labile synapses. This “genuine,” or mature, LTP rose from close to nothing of total LTP prior to postnatal day (P)13, to about 70% of total LTP at P16, and to about 90% of total LTP at P30. Developmental LTP, by stabilization of AMPA-labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.

Download Full-text