Objectives: Beta-amyloid (Abeta) is the principal component of senile plaques, which represent a prominent feature of Alzheimer s disease (AD). However, loss of neuronal function and cognitive impairment precedes Abeta plaque formation. We have previously reported that soluble Abeta oligomers impair synaptic transmission and plasticity in the entorhinal cortex, an area crucially involved in cognitive functions and early affected in AD. Recently 3-iodothyronamine (T1AM), a novel endogenous chemical messenger, was shown to stimulate memory acquisition in mouse. Our aim was to investigate whether T1AM can exert a protective effect versus Abeta-induced synaptic plasticity impairment. Methods: Synaptic function was studied recording extracellular field potentials evoked in cortical layers II III of entorhinal cortex slices; long term potentiation (LTP) was elicited by high frequency stimulation. T1AM concentration was measured by HPLC coupled to mass spectrometry. Results: We first evaluated the effects of T1AM perfusion, and identified a concentration (5 M) which does not interfere with either basal synaptic transmission or LTP induction and maintenance. As previously reported, Abeta oligomeric peptide at the concentration of 200 nM was capable of inhibiting LTP without affecting basic synaptic transmission. However perfusion with T1AM before high frequency stimulation delivery was able to rescue LTP in Abeta treated slices. Assaying endogenous T1AM concentration in the entorhinal cortex yielded values on the order of 6 pmol/g. Conclusions: Our results highlight the neuroprotective properties of T1AM, an endogenous thyroid hormone relative which can be detected in brain, and particularly in the entorhinal cortex. A better understanding of the mechanisms underlying the effect of T1AM against Abeta-induced neuronal dysfunction might allow the development of new pharmacological strategies to delay disease progression in AD patients.
3-Iodothyronamine rescues beta-amyloid dependent long term potentiation impairment in the enthorinal cortex
SABA, ALESSANDRO;ZUCCHI, RICCARDO;
2014-01-01
Abstract
Objectives: Beta-amyloid (Abeta) is the principal component of senile plaques, which represent a prominent feature of Alzheimer s disease (AD). However, loss of neuronal function and cognitive impairment precedes Abeta plaque formation. We have previously reported that soluble Abeta oligomers impair synaptic transmission and plasticity in the entorhinal cortex, an area crucially involved in cognitive functions and early affected in AD. Recently 3-iodothyronamine (T1AM), a novel endogenous chemical messenger, was shown to stimulate memory acquisition in mouse. Our aim was to investigate whether T1AM can exert a protective effect versus Abeta-induced synaptic plasticity impairment. Methods: Synaptic function was studied recording extracellular field potentials evoked in cortical layers II III of entorhinal cortex slices; long term potentiation (LTP) was elicited by high frequency stimulation. T1AM concentration was measured by HPLC coupled to mass spectrometry. Results: We first evaluated the effects of T1AM perfusion, and identified a concentration (5 M) which does not interfere with either basal synaptic transmission or LTP induction and maintenance. As previously reported, Abeta oligomeric peptide at the concentration of 200 nM was capable of inhibiting LTP without affecting basic synaptic transmission. However perfusion with T1AM before high frequency stimulation delivery was able to rescue LTP in Abeta treated slices. Assaying endogenous T1AM concentration in the entorhinal cortex yielded values on the order of 6 pmol/g. Conclusions: Our results highlight the neuroprotective properties of T1AM, an endogenous thyroid hormone relative which can be detected in brain, and particularly in the entorhinal cortex. A better understanding of the mechanisms underlying the effect of T1AM against Abeta-induced neuronal dysfunction might allow the development of new pharmacological strategies to delay disease progression in AD patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
