Interactions of Thyroid Hormones and Nerve Growth Factor in Normal Development of the Rat Hippocampus and Basal Forebrain and in Recovery From Early Hypothyroid Retardation

Abstract

We propose that decreased neural growth in hypothyroid animals and the robust rate of recovery is mediated by interactions of thyroid hormones with neurotrophins. We have found that hypothyroidism results in decreased hippocampal NGF levels, while up-regulating its receptors: the p75 neurotrophin and p140 trk A receptor. We propose that declining levels hippocampal NGF results in decreased trophic support for basal forebrain cholinergic neurons, leading to a compensatory up-regulation of NGF receptors. Thyroid hormone normalization restores total hippocampal NGF, causing hypertrophic growth responses in both the basal forebrain and hippocampal formation. Our findings present strong evidence for hippocampal plasticity lasting beyond the normal developmental period. This plasticity may be a result of regulatory and compensatory changes in neurotrophins and their receptors.