Neonatal thyroxine treatment: changes in the number of corticotropin-releasing-factor (CRF) and neuropeptide Y (NPY) containing neurons and density of tyrosine hydroxylase positive fibers (TH) in the amygdala correlate with anxiety-related behavior of wistar rats.
Neonatal hyperthyroidism induces persisting alterations in the adult brain, e.g. in spatial learning and hippocampal morphology. In the present study, the relationship between anxiety-related behavior and amygdala morphology was investigated in the adult rat after transient neonatal hyperthyroidism (daily s.c. injections of 7.5 microg L-thyroxine in 0.5 ml 0.9% NaCl solution from postnatal day p1 to p12). The behavioral tests used to study anxiety-related behavior were the motility test, elevated plus-maze and fear-sensitized acoustic startle response. In the amygdala, the number of neurons containing the anxiogenic peptide corticotropin releasing factor (CRF-ir and CRF mRNA) and anxiolytic neuropeptide Y (NPY-ir), the total number of neurons and the density of tyrosine hydroxylase immunoreactive (TH-ir) fibers were quantified. Thyroxine-treated pups presented an accelerated development including opening of eyes and snout elongation as typical signs of hyperthyroidism. Thyroxine-treated adult animals displayed a reduced anxiety in the motility box and elevated plus maze, a reduction in the number of CRF-ir neurons in the central nucleus of the amygdala, as well as an increase in the number of NPY-ir neurons and density of TH-ir fibers in nuclei of the basolateral complex of the amygdala. Moreover, there was a reduction in the total number of neurons in all nuclei of the basolateral complex (despite the higher number of NPY-ir neurons), but not central nucleus of the amygdala. The number of CRF-ir neurons in the central nucleus correlated positively with anxiety-related behavior, and the number of NPY-ir neurons and the density of TH-ir fibers in the basolateral complex correlated inversely with anxiety-related behavior. The findings suggested a shift toward an anxiolytic rather than anxiogenic distribution of peptidergic neurons and fibers in the amygdala at adult age following transient neonatal hyperthyroidism.
Institute of Anatomy, Otto-von-Guericke Universität Magdeburg, Institut für Anatomie, Leipziger Strasse 44, D-39120 Magdeburg, Germany. deniz.yilmazer-hanke@medizin.uni-magdeburg.de
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Yilmazer-Hanke
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Hantsch
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Hanke
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Schulz
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Faber-Zuschratter
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Schwegler
D000679:Amygdala / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004195:Disease Models, Animal; D004597:Electroshock / Q000379:methods; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009478:Neuropeptide Y / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D013216:Reflex, Startle / Q000187:drug effects; D013974:Thyroxine / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009478:Neuropeptide Y; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D013974:Thyroxine