The role of Pituitary Adenylate

Cyclase-activating Polypeptide (PACAP)

in learning during lifespan

By Francesca, Carlo, Nikolaos, Gayane, Yana, Charlotte, Hanna, Felisa

Application for Summer school Grants

Group 3: Molecular targets and neurodevelopment

-prevalence of neurodegenerative diseases, and aged population are increasing

- PACAP: - neuropeptide- spread through the brain- three receptors

- PACAP involved in learning and memory formation (PACAP receptor-deficient rats, receptor mutant mice)

- memory-related brain areas has not been investigated yet

- unknown if PACAP expression is changing during neurodevelopment.

Introduction

AIM OF THE STUDY

• To follow the expression of PACAP throughout lifespan in different brain regions.

• To detect changes in PACAP expression after a learning experience.

• To test the effect of PACAP and its analogues in models of memory deficit.

BEHAVIORAL STUDIES

In our experiment, in order to investigate the involvement\expression of PACAPergic system, we will use aversive learning paradigm

i.e. odor-shock conditioning

1 sec 30 secCS (odor)

1 sec4 min I.T.I.

shock: 0.5 mA

X 11

US

4 groups of Brown Norway male rats will be used

1: neonatal (PND 8)

2: juvenile (PND 27)

3: adult (PND 60)

4: aged rats (24 months)

From the Institute of Neurobehavioral studies, Zimbabwe: Preliminary results showed that the odor conditioning

protocol succeeded to induce stable odor memory 24 hours after the learning takes place

HISTOLOGY

Brain areas that will be investigated:

•Olfactory bulbs•LC (locus coeruleus)•Hippocampus•Amygdala

As control area: hypothalamus (PVN)

COLLABORATION

2. Institute of Neuroanatomy, Haiti (Nikolaos, Carlo, Gayane, Hanna)

1. Institute of Neurobehavioral studies, Zimbabwe (Yana, Felisa, Charlotte)

3. HOP (Help Old People) Pharmaceutical Co. (Francesca)

How it will work?

Institute of Neurobehavioral studies (Zimbabwe)

Behavior and tissues preparation

Institute of Neuroanatomy, (Haiti)

Molecular biology

HOP (Help Old People) Pharmaceutical Co. (Rome)

Drug supply

Expectations

• expression levels and distribution of PACAP throughout the brain will be significantly affected by learning and aging

• Different brain areas distribution of PACAP expression after the learning task at different developmental stages

• new perspectives in the field of learning and give new

targets for therapeutical intervention in memory loss disorders.

References

• Arimura A., Somogyvári-Vigh A., Miyata A., Mizumo K., Coy D.H., Kitada C., Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes, Endocrinology 129 (1991), pp. 2787–2789.

• Adamik A, Telegdy G. Effects of pituitary adenylate cyclase polypeptide (PACAP) on extinction of active avoidance learning in rats: involvement of neurotransmitters. Regul Pept. 2005 Apr 15;127(1-3):55-62.

• Sacchetti B., Lorenzini C.A., Baldi E., Bucherelli C., Roberto M., Tassoni G., Brunelli M., Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at very low dosages improves memory in the rat, Neurobiol. Learn. Mem. 76 (2001), pp. 1–6.

• Hashimoto H, Shintani N, Baba A. New insights into the central PACAPergic system from the phenotypes in PACAP- and PACAP receptor-knockout mice. Ann N Y Acad Sci. 2006 Jul;1070:75-89.

• Moriceau S., Wilson D.A., Levine S., Sullivan R.M., Dual Circuitry for Odor–Shock Conditioning during Infancy: Corticosterone Switches between Fear and Attraction via Amygdala.The Journal of Neuroscience, 2006 26(25):6737– 6748

For your attention

And special thanks for Krisztina and Sara

Please, give us a Grant, we want visit Haiti