Androgens modulate structure and function of the suprachiasmatic nucleus brain clock

Ilia N Karatsoreos; Matthew P Butler; Joseph Lesauter; Rae Silver

doi:10.1210/en.2010-1398

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Androgens modulate structure and function of the suprachiasmatic nucleus brain clock

Journal article

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Peer reviewed

Androgens modulate structure and function of the suprachiasmatic nucleus brain clock

Ilia N Karatsoreos, Matthew P Butler, Joseph Lesauter and Rae Silver

Endocrinology (Philadelphia), Vol.152(5), pp.1970-1978

05/2011

DOI: https://doi.org/10.1210/en.2010-1398

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https://hdl.handle.net/2376/106283

PMCID: PMC3075936

PMID: 21363939

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Abstract

Disks Large Homolog 4 Protein

Suprachiasmatic Nucleus - drug effects

Gene Expression - drug effects

Motor Activity - drug effects

Male

Intracellular Signaling Peptides and Proteins - metabolism

Glial Fibrillary Acidic Protein - metabolism

Biological Clocks - drug effects

Brain - metabolism

Motor Activity - radiation effects

In Situ Hybridization

Period Circadian Proteins - genetics

Time Factors

Light

Dihydrotestosterone - pharmacology

Suprachiasmatic Nucleus - metabolism

Membrane Proteins - metabolism

Synaptophysin - metabolism

Mice, Inbred C57BL

Brain - radiation effects

Circadian Rhythm

Gene Expression - radiation effects

Blotting, Western

Orchiectomy

Brain - drug effects

Microscopy, Confocal

Animals

Guanylate Kinases

Androgens - pharmacology

Biological Clocks - physiology

Biological Clocks - genetics

Mice

Gonadal hormones can modulate circadian rhythms in rodents and humans, and androgen receptors are highly localized within the core region of the mouse suprachiasmatic nucleus (SCN) brain clock. Although androgens are known to modulate neural plasticity in other CNS compartments, the role of androgens and their receptors on plasticity in the SCN is unexplored. In the present study, we ask whether androgens influence the structure and function of the mouse SCN by examining the effects of gonadectomy (GDX) on the structure of the SCN circuit and its responses to light, including induction of clock genes and behavioral phase shifting. We found that after GDX, glial fibrillary acidic protein increased with concomitant decreases in the expression of the synaptic proteins synaptophysin and postsynaptic density 95. We also found that GDX exerts effects on the molecular and behavioral responses to light that are phase dependent. In late night [circadian time (CT)21], GDX increased light-induced mPer1 but not mPer2 expression compared with intact (INT) controls. In contrast, in early night (CT13.5), GDX decreased light induced mPer2 but had no effect on mPer1. At CT13.5, GDX animals also showed larger phase delays than did INT. Treatment of GDX animals with the nonaromatizable androgen dihydrotestosterone restored glial fibrillary acidic protein, postsynaptic density 95, and synaptophysin in the SCN and reinstated the INT pattern of molecular and behavioral responses to light. Together, the results reveal a role for androgens in regulating circuitry in the mouse SCN, with functional consequences for clock gene expression and behavioral responses to photic phase resetting stimuli.

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Title: Androgens modulate structure and function of the suprachiasmatic nucleus brain clock
Creators: Ilia N Karatsoreos - Department of Psychology, Columbia University, New York, New York 10027, USA
Matthew P Butler
Joseph Lesauter
Rae Silver
Publication Details: Endocrinology (Philadelphia), Vol.152(5), pp.1970-1978
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: T32 DK007328 / NIDDK NIH HHS R01 NS037919 / NINDS NIH HHS NS37919 / NINDS NIH HHS T32DK07328 / NIDDK NIH HHS
Identifiers: 99900546631101842
Language: English
Resource Type: Journal article