PS 07-19 KNOCKDOWN OF P38 MAPK IMPROVES HIPPOCAMPAL SYNAPTIC PLASTICITY IN ANGIOTENSIN II-DEPENDENT HYPERTENSIVE MICE

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Abstract

Objective:

The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, new molecular targets are needed. Synaptic plasticity is the neurobiological basis of learning and memory. p38 MAPK signalling pathway plays an important role in hypertensive target organ damage and synaptic plasticity. To examine whether there is a link between p38 MAPK and hippocampal synaptic plasticity in angiotensin II-dependent hypertensive mice.

Design and Method:

We used p38 heterozygous knockdown mouse (p38KI/+). 2 month old p38KI/+ and wild type (WT) mice were infused via minipump with angiotensin II or saline solution as a control. Post-tetanic potentiation(PTP) and Long-term potentiation(LTP) were measured by vitro electrophysiology on hippocampal slices at the Schaffer-CA1 pathway. Data of fEPSP slopes during 0–10 min (i.e. PTP) and 50–60 min(i.e. LTP) after theta burst stimuli application were summarized and compared.

Results:

The treatment of angiotensin II significantly raised the systolic blood pressure constant throughout the experiment in p38KI/+ and WT mice (p < 0.01). No unequivocal change was found for the I/O curves of the various treatment conditions(all P > 0.05). Compared to control WT mice, hippocampal CA1 PTP and LTP were decreased in angiotensin II-dependent hypertensive WT mice (p < 0.05). In angiotensin II-treated hypertensive p38KI/+ mice, hippocampal synaptic plasticity was improved, compared to hypertensive WT mice (p < 0.05).

Results:

Ion were summarized and compared.

Conclusions:

Knockdown of p38 MAPK improves hippocampal synaptic plasticity in angiotensin II-dependent hypertensive mice. p38 MAPK inhibition may provide a new target for the treatment of hypertension-related cognitive dysfunction.

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