Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor.
Hyperthyroidism, induced in rat pups by the daily intraperitoneal administration of 1 microgram/g body weight triiodothyronine, facilitated the development of ChAT fiber plexuses in brain regions innervated by basal forebrain cholinergic neurons, leading to an earlier and increased expression of cholinergic markers in those fibers in the cortex, hippocampus and amygdala. A similar enhancement was seen in the caudate-putamen complex. This histochemical profile was correlated with an accelerated appearance of ChAT-positive telencephalic puncta, as well as with a larger total number of cholinergic terminals expressed, which persisted throughout the eight postnatal week, the longest time examined in the present study. Hypothyroidism was produced in rat pups by adding 0.5% propylthiouracil to the dams' diet beginning the day after birth. This dietary manipulation resulted in the diminished expression of ChAT in forebrain fibers and terminals. Hypothyroid treatment also reduced the quantity of ChAT puncta present during postnatal weeks 2 and 3, and, from week 4 and continuing through week 6, the number of ChAT-positive terminals in the telencephalic regions examined was actually less than the amount extant during the former developmental epoch. Immunostaining for nerve growth factor receptor (NGF-R), which is associated almost exclusively with ChAT-positive somata and fibers in the basal forebrain, demonstrated a different time course of postnatal development. Forebrain fibers and terminals demonstrating NGF-R were maximally visualized 1 week postnatally, a time at which these same neuronal elements evinced minimal ChAT-like immunopositivity. Thereafter and correlated with increased immunoreactivity for ChAT, fine details of NGF-R stained fibers were observed less frequently. Although propylthiouracil administration decreased NGF-R immunodensity, no alteration in the development of that receptor was observed as a function of triiodothyronine treatment. Cholinergic terminals in the ventrobasal thalamus, which derive from ChAT-positive neurons in the pedunculopontine and laterodorsal tegmental nucleus, were unaffected by either hyperthyroid or hypothyroid conditions. These cells also do not demonstrate NGF-R. We conclude from these experiments (1) that cholinergic fiber plexuses eventually exhibiting ChAT positivity in the telencephalon demonstrate NGF-R prior to the cholinergic synthetic enzyme, (2) that susceptibility to thyroid hormone manipulations may involve sensitivity to NGF, at least in some forebrain cholinergic systems and (3) that the effects of thyroid hormone imbalances on brain cholinergic neurons are regionally selective.
Oh
J D
JD
Department of Psychology, University of California, Los Angeles, 90024-1563.
Butcher
L L
LL
Woolf
N J
NJ
D000375:Aging / Q000502:physiology; D000679:Amygdala / Q000187:drug effects / Q000254:growth & development; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development; D007150:Immunohistochemistry; D008297:Male; D009411:Nerve Endings / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor; D013564:Sympathetic Nervous System / Q000254:growth & development* / Q000502:physiology; D013687:Telencephalon / Q000033:anatomy & histology / Q000201:enzymology / Q000254:growth & development; D013963:Thyroid Hormones / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D013963:Thyroid Hormones; D014284:Triiodothyronine; D002795:Choline O-Acetyltransferase