7/30/2019 Ravi Chandra POSTER (2)

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Minocycline prevents cerebral malaria and cognitive decline in

Plasmodium berghei infected miceRavi Chandra K. , Apoorv Thittayil Suresh, Prof. P. PrakashBabu*

Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad-500 046, India

INTRODUCTION

Cerebral malaria (CM) is the neurological complication caused by

infection of protozoanPlasmodium falciparum and Plasmodium vivax.

Major clinical symptoms include convulsions, dyspnea, sudden

bleeding, abnormal body posturing, coma and death. It affects 5-10%

of the malarial patients and is the main reason for death. Antimalarial

combination therapies are able to rescue some of the patients but the

CM survivors continue to suffer from cognitive impairment later in

their lives. Poor prognosis and post-regimen cognitive decline makes

CM an important area of research for discovery of novel adjunctive

therapies with neuroprotective properties.

Minocycline (MC), a semi-synthetic tetracycline, has been found to be

reliable in neurodegenerative disorders like spinal cord injury,

ischemia, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimers

disease, Parkinsons disease and Huntingtons disease. As one of the

reasons for CM is the cytokine storms produced in brain and

minocycline has the ability to decrease the inflammatory cytokines, we

hypothesize that minocycline might be neuroprotective in CM too.

OBJECTIVES

1. To calculate the effect of MC on the survivability ofPbA infected mice2. To assess the cognitive impairment/improvement in MC treated mice3. To evaluate dendritic spine morphology and density difference in

infected and MC treated mice

METHODOLOGY

InfectedControl MC

45mg/kgBodyWeight

C57BL/6mousewith5-10%

ascendingparasitemia

Spatial Learning and Memory

T-Maze for checking memory retention

Non-Spatial Learning and Memory

Novel Object Recognition (NOR) Test for checking Retrograde

Amnesia

Bow Tie Maze NOR Test - for checking Anterograde Amnesia

Assessment of Social Approach Behaviour using 3 chamber apparatus

Depression - Marble burying ability

INFECTION

Neurological

Symptoms&death

duetoCM

SevereAnemicmice

dieonday14-15

Parasiteclearedin

MCtreatedmice&

survive2months

1.

2.

3. Golgi Cox staining for dendritic morphology

For studying both the normal and abnormal morphology of neurons

STATISTICAL ANALYSIS OF ALL PARAMETERS using

Graph pad prism software expressed as mean SEM

RESULTS

Non-Spatial Learning and Memory

Novel Object Recognition (NOR) Test

Bow Tie Maze NOR Test for Anterograde Amnesia

KaplanMeiersurvivalcurve

Survivability ofPbA infected mice Spatial Learning and Memory

T-Maze

Social Approach Behaviour

Golgi Cox staining

Bow-TieMaze

Marble burying ability

3-ChamberApparatus

Control MinocyclineTreatedInfected

Control Hippocampus (4X Objective) Control Hippocampal Dendrite

(100X Objective)

CONCLUSION

Minocycline improves the cognitive outcome in PbA infeced mice and is a promising drug

for human clinical trials.

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