Reorganization of mossy fiber synapses in male and female hypothyroid rats: A stereological study

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Abstract
Thyroid hormone deficiency has been reported to interfere with synaptogenesis, particularly in those regions of the brain where the neurons display a late and protracted histogenesis, although the extent of the synaptic alterations remains unknown. To provide detailed quantitative data on the effects of hypothyroidism upon synapses, a link of the hippocampal circuitry was selected: the contact between mossy fibers and dendritic excrescences of CA3 pyramidal cells (MF-CA3 synapses). Groups of six male and six female rats aged 30 and 180 days were analyzed separately after being treated as follows: (1) hypothyroid from day 0 until day 30 (30 day old hypothyroid group); (2) hypothyroid from day 0 until day 180 (180 day old hypothyroid group); (3) hypothyroid until day 30 and thenceforth maintained euthyroid (recovery group); and (4) and (5) 30 and 180 day old control groups, respectively. Timm staining, Golgi impregnation, and electron microscopy were employed to estimate the volume of the mossy fiber system, the number and size of mossy fiber boutons, and the number and related features of MF-CA3 synapses. The volume of the mossy fiber system and the number of synaptic boutons were reduced in all experimental groups. The total number of synapses was decreased in 30 day old hypothyroid rats, but did not differ among 180 day old animals. Postsynaptic densities were shorter in hypothyroid and recovery groups than in controls, although the reduction was not as marked in recovery rats as it was in hypothyroid animals. Structural alterations were noted in the pre- and postsynaptic compartments of MF-CA3 synapses of both 180 day old hypothyroid and recovery rats. These changes can be regarded as mechanisms of reorganization as they underlie the compensation for the hypothyroid-induced numerical reduction of synapses observed in 30 day old animals and enable a complete catch-up of their total number. However, synaptic reorganization was not fully achieved, as revealed by the reduction in the size of the synaptic sites in hypothyroid and recovery animals. Finally, we demonstrate that hypothyroidism did not interfere with the sex-related differences of MF--CA3 synapses described in normal rats.