title: Androgens modulate structure and function of the suprachiasmatic nucleus brain clock.
abstract: 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.
authors.affiliation: Department of Psychology, Columbia University, New York, New York 10027, USA.
authors.forename: Ilia N
authors.initials: IN
authors.lastname: Karatsoreos
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Butler
authors.forename: Joseph
authors.initials: J
authors.lastname: Lesauter
authors.forename: Rae
authors.initials: R
authors.lastname: Silver
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002940:Circadian Rhythm; D013196:Dihydrotestosterone / Q000494:pharmacology*; D000076122:Disks Large Homolog 4 Protein; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051528:Guanylate Kinases; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008027:Light; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D009919:Orchiectomy; D056950:Period Circadian Proteins / Q000235:genetics; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000728:Androgens; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D016708:Synaptophysin; D013196:Dihydrotestosterone; D051528:Guanylate Kinases