Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating.
One of the primary lines of defense against oxidative stress is the selenoprotein family, a class of proteins that contain selenium in the form of the 21st amino acid, selenocysteine. Within this class of proteins, selenoprotein P (Sepp1) is unique, as it contains multiple selenocysteine residues and is postulated to act in selenium transport. Recent findings have demonstrated that neuronal selenoprotein synthesis is required for the development of parvalbumin (PV)-interneurons, a class of GABAergic neurons involved in the synchronization of neural activity. To investigate the potential influence of Sepp1 on PV-interneurons, we first mapped the distribution of the Sepp1 receptor, ApoER2, and parvalbumin in the mouse brain. Our results indicate that ApoER2 is highly expressed on PV-interneurons in multiple brain regions. Next, to determine whether PV-interneuron populations are affected by Sepp1 deletion, we performed stereology on several brain regions in which we observed ApoER2 expression on PV-interneurons, comparing wild-type and Sepp1(-/-) mice. We observed reduced numbers of PV-interneurons in the inferior colliculus of Sepp1(-/-) mice, which corresponded with a regional increase in oxidative stress. Finally, as impaired PV-interneuron function has been implicated in several neuropsychiatric conditions, we performed multiple behavioral tests on Sepp1(-/-) mice. Our behavioral results indicate that Sepp1(-/-) mice have impairments in contextual fear extinction, latent inhibition, and sensorimotor gating. In sum, these findings demonstrate the important supporting role of Sepp1 on ApoER2-expressing PV-interneurons.
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, HI 96813, USA. mwpitts@hawaii.edu
M W
MW
Pitts
A V
AV
Raman
A C
AC
Hashimoto
C
C
Todorovic
R A
RA
Nichols
M J
MJ
Berry
D000818:Animals; D005239:Fear / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics; D010320:Parvalbumins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051149:Selenoprotein P / Q000172:deficiency* / Q000235:genetics; D055139:Sensory Gating / Q000235:genetics*
D010320:Parvalbumins; D051149:Selenoprotein P