dementia-2016_scientifictracks-abstracts

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Dementia 2016

September 29-October 01, 2016

Volume 6 Issue 5(Suppl)

J Alzheimers Dis Parkinsonism 2016

ISSN:2161-0460 JADP, an open access journal

conferenceseries

.com

September 29-October 01, 2016 London, UK

International Conference on

Alzheimer’s Disease & Dementia

Shahnawaz Ali Bhat et al., J Alzheimers Dis Parkinsonism 2016, 6:5(Suppl)

Platelet CD40Lmediates activation of Astrocytes and Microglia culminating in Neuronal injury in

brain regions associated with Memory functions during Chronic Hypertension

Shahnawaz Ali Bhat, Ruby Goel, Rakesh Shukla

and

Kashif Hanif

CSIR-Central Drug Research Institute, India

tudies have reported hypertension as a prominent risk factor for dementia. Further, earlier reports have separately

demonstrated that chronic hypertension is associated with platelet activation in periphery (resulting in accumulation

and localized inflammatory response) and glial activation in brain. We investigated the contribution of platelets in brain

inflammation, particularly glial activation and associated neuronal injury

in vitro

and in a rat model of chronic hypertension.

We found that chronic HTN increased the expression of adhesion molecules like JAM-1, ICAM-1 and VCAM-1 on brain

endothelium and resulted in the deposition of platelets in brain. Platelet deposition in chronic hypertension was associated

with the augmented CD40 and CD40L and activation of astrocytes (GFAP expression) and microglia (Iba-1 expression) and

increased caspase 3 expression and more TUNEL positive cells in the brain. Platelets isolated from hypertensive rats had

significantly higher sCD40L level and induced prominent glial activation than platelets from normotensive rats. Moreover,

CD40L induced astrocyte and microglia activation and NFкB and MAPK inflammatory signaling, with subsequent release

of inflammatory TNF-α. Remarkably, conditioned media from CD40L activated glia induced the apoptosis in neuronal cells,

Neuro2A (evidenced by increased Annexin V/PI +ve cells via flowcytometry). On the contrary, inhibition of platelet activation

by clopidogrel or disruption of CD40 signaling prevented astrocyte and microglial activation and provided neuroprotection in

both

in vivo

and

in vitro

conditions. Thus, we have identified platelet CD40L as a key inflammatory molecule for the induction

of astrocytes and microglia activation, the major contributors of inflammation mediated neurodegeneration in brain.