8/13/2019 RSC MU 2013

1/21

1

The Insight of Chronobiology with

an Emphasis on the Nightly Surge

of Serotonin Output in the RatPineal Gland and the Role of TPH1

Asamanja Chattoraj, PhD

Scient is t -D; Anim al Bioresources ProgrammeINSTITUTE OF BIORESOURCES & SUSTAINABLE DEVELOPMENT (IBSD)

DEPARTMENT OF BIOTECHNOLOGY, GOVERNMENT OF INDIA

Takyelpat, Imphal795001, Manipur (India)

Email: achattoraj.ibsd@nic.inasamanja.chattoraj@gmail.com

8/13/2019 RSC MU 2013

2/21

2

What is chronobiology?

Biological rhythm persisting as a fundamental property of biologic entities under various

conditions of presumed constancy in environmental factors.

The formal study of biological temporal rhythms such as daily, tidal, weekly, seasonal,

and annual rhythms is called chronobiology.

A circadian rhythm is an endogenously driven roughly 24-hour cycle in biochemical,

physiological, or behavioural processes.

Circadian rhythms have been widely observed, in plants, animals, fungi and

cyanobacteria.

The term "circadian" comes from the Latin

circa, meaning "around", and

diem or

dies,

meaning "day".

Although circadian rhythms are endogenous ("built-in", self-sustained), they are adjusted

(entrained) to the environment by external cues called zeitgebers, the primary one of

which is daylight.

8/13/2019 RSC MU 2013

3/21

8/13/2019 RSC MU 2013

4/21

4

Travelling of Light into the Mammalian Pineal Gland

8/13/2019 RSC MU 2013

5/21

8/13/2019 RSC MU 2013

6/21

Importance of Melatonin and Serotonin

Serotonin:

Neurotransmitter

Control of appetite Sleep Memory and learning Temperature regulation Mood Behavior (including sexual and hallucinogenic behavior) Cardiovascular function Muscle contraction Endocrine regulation Depression

Melatonin:

Sleep-Wakefulness Cycle Reproduction

Hibernation Hypertension Cell Proliferation Seasonal Affective Disorders Immune-Response Jet-lag Scavenger of Free Radicals

Aging 6

8/13/2019 RSC MU 2013

7/21

The pineal gland of all vertebrates produces 5-HT.

The synthesis of 5-HT from tryptophan requires two enzymes:

a) Tryptophan Hydroxylase 1(TPH1) which limits the rate of 5-HT production and

b) Aromatic Amino Acid Decarboxylase,constitutively expressed at high levels.

TPH1 enzyme activity displays a two fold increase in the night pineal gland of rats.

A number of studies points to an essential role of -adrenargic signallingin the

regulation of TPH1 activity.

In vitro studies also pointed out the role of cAMP and PKAin the activity of TPH1.

PKA phosphorylates TPH1 in vitro at serine 58 residue.

It remains unknown , whether PKA elevates TPH1 activity by increasing its protein

stability and whether TPH1 is phosphorylated in v ivo at the S58 site.

Existing Information

7

8/13/2019 RSC MU 2013

8/21

Aims of the Present Study

The regulation of nocturnal increase of 5-HT total

output in the night pineal gland.

The role of cAMP signaling in 5-HT synthesis in vivo.

The role of TPH1 phosphorylationin the regulation of

TPH1 protein content.

8

8/13/2019 RSC MU 2013

9/21

DARKLIGHT

TPH1 mRNA Expression is NOT Under Circadian Control In Rat Pineal

99

8/13/2019 RSC MU 2013

10/21

Night-time TPH1 mRNA Expression is INSENSIBLE to Light Exposure

1010

1: No Light

2: 10 mints Light

3: 24 hr Light

8/13/2019 RSC MU 2013

11/21

Measurement of Pineal Indoleamines by Microdialysis

11

8/13/2019 RSC MU 2013

12/21

5-HT Total Output and TPH1 Protein Levels Display

Dramatic Circadian Rhythms

12

8/13/2019 RSC MU 2013

13/21

Cyclic AMP Signaling in the Pineal Gland Stimulates

the Total Output of 5-HT in v ivo

13

8/13/2019 RSC MU 2013

14/21

TPH1 is Phosphorylated at the S58 in the Night Pineal Gland

14

8/13/2019 RSC MU 2013

15/21

8/13/2019 RSC MU 2013

16/21

Light Pulses at Night Suppress the Nocturnal Increase of both 5-

HT Total Output and TPH1 Protein Levels in the Living Pineal Gland

16

8/13/2019 RSC MU 2013

17/21

Conclusion and Summary

17

8/13/2019 RSC MU 2013

18/21

18

Melatonin as Bioindicator for Oocyte

maturation in carp.

Fish Gut Microflora and Melatonin: A

Chronobiological Study on Indian Major

Carp

Current Research

8/13/2019 RSC MU 2013

19/21

19

The Group

8/13/2019 RSC MU 2013

20/21

Acknowledgement

20

I am grateful to my mentor Prof. S.K. Maitra,

Department of Zoology, Visva-Bharati, West-Bengal,INDIA, for everything I have learned and still learningfrom him.

I am thankful to Dr Jimo Borjigin,MIP, Universityof Michigan, USA For helping me in my post-doctoralstudies.

Financial Support from United States Air force and

NIH, USA, are thankfully acknowledged.

8/13/2019 RSC MU 2013

21/21

21