Selective vulnerability of the hippocampal pyramidal neurons to hypothyroidism in male and female rats

Abstract

Thyroid hormone deficiency has long been considered to affect profoundly such cognitive functions as learning and memory, which are known to depend on the structural integrity of the hippocampal formation. Since we previously found that the number of granule cells of the dentate gyrus is reduced in hypothyroid animals, we decided to extend our observations to the pyramidal cells of the hippocampus in order to gain further insight into the effects of hypothyroidism upon the other neuronal links of the hippocampal trisynaptic circuitry, inasmuch as CA1 neurons are known to be particularly vulnerable to aggressive agents. Groups of 6 male and 6 female rats aged 30 and 180 days were analysed separately after being treated as follows: (1) hypothyroid from day 0 until day 30 (30-day-old hypothyroid group); (2) respective 30-day-old control; (3) hypothyroid from day 0 until day 180 (180-day-old hypothyroid group); (4) hypothyroid until day 30 and thenceforth maintained euthyroid (recovery group); (5) hypothyroid since day 30 (adult hypothyroid group); and (6) respective 180-day-old control. The volume of the pyramidal cell layer of the CA1 and CA3 regions and the numerical density of the respective neurons were evaluated, thereby allowing us to estimate the total number of pyramidal cells in each hippocampal region. The areal density and the mean nuclear volume of CA1 and CA3 pyramidal cells were also estimated. In the CA3 region, we found that hypothyroidism, whatever its duration and time of onset, induces a reduction in the volume of the pyramidal cell layer and a parallel increase in the numerical density of its neurons, without interfering with the total number of pyramidal cells. Conversely, in the CA1 region, thyroid hormone deficiency started either neonatally or during maturity was found to lead to a decrease in the total number of pyramidal cells. Reductions ranging between 14.2 and 22.5% were found in 30 and 180-day-old hypothyroid groups. The reestablishment of a euthyroid state did not ameliorate the referred neuronal loss. The present results support the view that hypothyroidism induces small alterations in the structural organization of the hippocampal CA3 region, contrary to what happens in CA1 in which neuronal death occurs. Furthermore, the data presented herein demonstrate that the total number of CA1 pyramidal cells displays sexual dimorphism that is not affected by thyroid hormone manipulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyroidal dysfunction and environmental chemicals--potential impact on brain development.

“…Maturation and synaptic development of the pyramidal cells of the hippocampus are particularly sensitive to thyroid hormone deficiency during fetal/perinatal development (18). Early in fetal development (rats), thyroid hormone deficiency decreases radial glial cell maturation and therefore impairs cellular migration (19) …”

Effects of adult dysthyroidism on the morphology of hippocampal neurons

“…However, only in CA1 the total 50 number of pyramidal neurons was reduced by adult hypothy-51 roidism [26]. Nevertheless, Alva-Sánchez et al [27] found that short-term adult-onset hypothyroidism impairs 56 dendritic arborization of immature neurons.…”

“…In adulthood, hypothyroidism also decreases the weight of 48 the hippocampus [25,26] and the volume of the pyramidal neurons in CA3 and CA1 [26]. However, only in CA1 the total 50 number of pyramidal neurons was reduced by adult hypothy-51 roidism [26].…”

Thyroid Hormone Effects on Sensory Perception, Mental Speed, Neuronal Excitability and Ion Channel Regulation

“…At the morphological level, in the mature brain thyroid hormone excess (149) as well as deficiency (150) have been reported to decrease the number of dendritic spines, assumed to represent postsynaptic endings, already after 5 days in adult rats. Even more dramatically, hypothyroidism leads to a reduction of the neuropile in CA1 and CA3 hippocampal areas and in addition to a loss of pyramidal cells in the CA1 area (151). Thus it seems possible that adult-onset hypothyroidism may actually cause neuronal degeneration, as already occasionally observed in autopsies of early cases of patients who had died with myxedema (152,153).…”