Neonatal neurosteroid administration alters parvalbumin expression and neuron number in medial dorsal thalamus of adult rats.
The neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) is a potent endogenous modulator of GABAA receptor function. A single neonatal allopregnanolone administration (10 mg/kg, i.p.) was previously shown to alter the localization of parvalbumin-positive neurons in the prefrontal cortex at maturity. Cells in the prefrontal cortex receive the majority of their inputs from the medial dorsal nucleus of the thalamus. We investigated whether neonatal allopregnanolone administration alters the neuronal population of the medial dorsal nucleus of the thalamus. We show that the number of parvalbumin-expressing neurons is increased while the total neuron number is decreased in the medial dorsal nucleus after allopregnanolone administration. EAAT3 (excitatory amino acid transporter type 3, the neuron-specific glutamate reuptake transporter) immunoreactivity was unchanged in adjacent sections. These findings suggest that neonatal allopregnanolone administration disrupts the normal development of the prefrontal cortex and medial dorsal thalamus, indicating that neurosteroid levels are important for proper development of thalamocortical systems and may play a role in neurodevelopmental disorders such as schizophrenia.
Gizerian
Samantha S
SS
Curriculum in Neurobiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Morrow
A Leslie
AL
Lieberman
Jeffrey A
JA
Grobin
A Chistina
AC
D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010320:Parvalbumins / Q000096:biosynthesis*; D011247:Pregnancy; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000096:biosynthesis
D027322:Amino Acid Transport System X-AG; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D010320:Parvalbumins; C493398:Slc1a1 protein, rat; D027981:Symporters; D011280:Pregnanolone