MicroRNA and Memory Deficits in Aging

8/10/2019 MicroRNA and Memory Deficits in Aging

1/13

MicroRNA Scientific InterestGroup

University of California San Diego

Erick [email protected]

First MeetingOctober 14, 2014
mailto:[email protected]


2/13

4:00 - 4:05 Introduction

4:05 - 4:20 Study of MicroRNA and Memory

Deficits in Aging

4:20 - 4:50 Sketches of miRNA Regulation in T

and B Cells: Prospects for

Immunogenomic Therapy

4:50 - 5:00 Discussion

AGENDA


3/13

MicroRNA and Memory Deficits inAging

Erick T. TatroDepartment of Psychiatry, UC San Diego

October 14, 2014


4/13

Sam and Rose Stein Institute for Research on Aging

Young vs Aged Mouse

Some Aged Mice Exhibit Memory Deficit

BACKGROUND Model Mammal

ObjectDiscriminationRatio(DR)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Young Old

ImpairedNormalNormal

Aged

Training Phase

Testing Phase

?


5/13

Mouse - TaqMan Low Densi ty Array (384 wells)

MIRNA ARRAY Hippocampus

-0.4

-0.3

-0.2

-0.1

0.0

0.1

0.2

0.3

0.4

Legend

miR-130b

miR-138

miR-222

miR-29b

miR-339-3p

miR-340-5p

miR-582-3p

Young Aged

NormalNormal ImpairedLog

(Fold

Control)Expression

Tatro & Scott et al. PLOS One(2010)


6/13

Validate & ImageRESULTSQ PCR

Young Old

ImpairedNormalNormal

In Situ Hybridization

MiR-138

Whole Brain

Hippocampus

Whole Brain

Hippocampus

Young

Aged /

Impaired

MiR-138

Aged

Exiqon Corporation


7/13

Target of miR138SIGNIFICANCE

S SH

APT1

APT1mRNA

miR-138

Palmitoylation of Proteins in Dendritic Spine

Stable Extend

Acyl Protein Thioesterase 1


8/13

Target of miR138RESULTS

APT1-mR

NA

-0.25

0.00

0.25

0.50

0.75

1.00 GroupYoung

Aged Unimpaired

Aged Impaired

Young Aged

NormalNormal Impaired

Q PCR In Situ Hybridization

Acyl ProteinThioesterase

Acyl ProteinThioesterase

Whole Brain

Dentate Gyrus

Hippocampus Aged


9/13

Serial SectionsRESULTS

miR-138 APT1 Protein

Dentate

Gyrus

Aged /

Impaired

Young

Tatro et al. Am J Geriatric Psych. (2013)


10/13

CONCLUSION Age associated memory impairment correlated

with lower miR-138 expression, particularly inthe hippocampus.

FURTHERSTUDY Examine miR - mediated syanptodendritic

changes. Examine causes of differential miR-138

regulation: epigenetics, transcription factors,

HPA axis homeostasis.


11/13

THANKYOU Department of Psychiatry

Cristian Achim, Ian Everall, Mariana Cherner, Svetlana Semenova, David Moore, IgorGrant, Hamp Atkinson

Eliezer Masliah, Erick Scott

Ben Soontornniyomkij, Virawudh Soontornniyomkij, Silke Nuber, Ben Guoux, MichaelYang, Intan Purnajo, Alex Yermanos

Sam and Rose Stein Institute for Research on Aging Dillip Jeste, Vicki Risbrough, Jared Young

UC San Diego Center for AIDS Research

Virology Core

Davey Smith, Sara Gianella, Doug Richman

Genomics Core

Christopher Woelk, Steffney Rought, Pinyi Du

HIV Neurobehavioral Research Programs

Exiqon Corporation (Small Grants Award for Supplies)

NIDA (R03DA031591) and NIMH


12/13

4:00 - 4:05 Introduction

4:05 - 4:20 Study of MicroRNA and MemoryDeficits in Aging

4:20 - 4:50 Sketches of miRNA regulation in T and

B cells: Prospects for immunogenomic

therapy

4:50 - 5:00 Discussion

AGENDA


13/13

MicroRNA Scientific InterestGroup

University of California San Diego

Erick [email protected]

First MeetingOctober 14, 2014
mailto:[email protected]

MicroRNA and Memory Deficits in Aging

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