Novel two-dimensional morphometric maps and quantitative analysis reveal marked growth and structural recovery of the rat hippocampal regions from early hypothyroid retardation

Abstract

Effects of postnatal hypothyroidism and recovery from this condition on regional growth of the rat hippocampus (HC) were studied using two-dimensional (2D) foldout, morphometric maps of HC and its constituent CA1-CA4 regions. The maps were derived from unfolding serial coronal sections of the rat forebrain, consisting of the entire rostrocaudal extent of HC pyramidal cell layer in the normal control and hypothyroid weanling (P25, postnatal day 25) and young adult (P90) male rats, as well as animals allowed to recover from hypothyroid-induced growth retardation at weaning. The maps revealed novel views of HC regions for assessment of topological relationships and measurement of surface areas of the HC cortical sheet (pyramidal cell layer). In normal control P90 rats, the unfolded HC on each side extended 4 times more laterally than rostrocaudally; total HC surface area was about 40 mm 2 , compared to 30 mm 2 in the weanling, indicating 35% growth from P25 to P90; CA1 took up 52% of the total HC surface area, followed by CA3 (31%) and CA2 and CA4, 8% each. Hypothyroidism resulted in significant (p<0.01) 11% and 20% reductions in the HC surface area in P25 and P90 rats respectively; CA1 and CA4 regions suffered the most reductions while CA3 and CA2 regions the least. Recovering rats examined at P90, exhibited remarkable growth plasticity and recovery in HC regions, as evident by their near normal HC cortical surface area values, compared to age-matched controls. The 2-D maps also revealed growth deficits in all HC regions of the hypothyroid rats; recovery in these parameters occurred across all dimensions, although the anterior-posterior growth was more severely affected than the mediolateral one. These results are confirmed and extended by volumetric analysis of laminar volumes of HC regions presented in a companion paper (Farahvar et al., 2006). These results imply that HC regions, in contrast to whole brain, possess exceptional growth plasticity, as shown by ability to dramatically recover from early hypothyroid retardation; also 2D morphometric maps are useful tools to visualize complex and convoluted regional sheet of HC cortex and depict quantitative aspects of growth in normal and experimental conditions.

Differential effects of developmental hypo‐ and hyperthyroidism on acetylcholinesterase and butyrylcholinesterase activity in the spinal cord of developing postnatal rat pups

“…In addition to reductions in body weight, the hypothyroid pups showed all the classical signs of developmental hypothyroidism such as delayed eye and ear opening, infantile fur and reduced movements and playing activity. These results were very similar to our previously published reports (Farahvar and Meisami, 2007; Paternostro and Meisami, 1993). Interestingly, while the body weights of the hyperthyroid pups were generally unaffected by the treatment, they all showed all the classic signs of developmental hyperthyroidism in the rat, such as accelerated body development and maturation, earlier eye and ear opening, and earlier development of fur and facies, and an apparent reduction in body fat, as reported in our previous publications (see Paternostro and Meisami, 1991).…”

“…Following our previously published procedures (Farahvar and Meisami, 2007; Paternostro and Meisami, 1993; Tamasy et al, 1986a,b), developmental hypothyroidism was induced by adding the antithyroid goitrogen, propylthiouracil (PTU, 6‐n‐propyl‐2‐thiouracil; Sigma, St. Louis) to the drinking water of the litter at a concentration of 0.1% (w/v), from birth till the days of sacrifice (P1, P5, P10 and P21). On the recommendation of the University of Illinois veterinarian and following the practice described in our previous publications (Farahvar and Meisami, 2007; Paternostro and Meisami, 1993; Tamasy et al, 1986a,b), a small amount of a non‐caloric sweetener (saccharin) was added to the water bottles of the hypothyroid litters, at the concentration of 0.01 mg/L, to mask the bitter taste of PTU and prevent reduced water intake. Our previous studies have shown that PTU administration plus the artificial sweetener results in adequate water intake, decreased plasma T 4 levels by 100% and a several‐fold increase in plasma TSH levels (Farahvar and Meisami, 2007; Paternostro and Meisami, 1991, 1993; Tamasy et al, 1986a,b).…”

“…On the recommendation of the University of Illinois veterinarian and following the practice described in our previous publications (Farahvar and Meisami, 2007; Paternostro and Meisami, 1993; Tamasy et al, 1986a,b), a small amount of a non‐caloric sweetener (saccharin) was added to the water bottles of the hypothyroid litters, at the concentration of 0.01 mg/L, to mask the bitter taste of PTU and prevent reduced water intake. Our previous studies have shown that PTU administration plus the artificial sweetener results in adequate water intake, decreased plasma T 4 levels by 100% and a several‐fold increase in plasma TSH levels (Farahvar and Meisami, 2007; Paternostro and Meisami, 1991, 1993; Tamasy et al, 1986a,b).…”

“…Body weights and appearance of developmental landmarks (ear and eye opening, changes in facies, fur growth, mobility, etc.) were checked for hypo‐ and hyperthyroid conditions, per our previous procedures and reports (Paternostro and Meisami, 1991, 1993; Farahvar and Meisami, 2007).…”

“…Thyroid hormones (TH) have profound effects on the developing central nervous system of mammals (see Eayrs, 1971; Farahvar and Meisami, 2007; Lauder, 1977; Legrand, 1982; Meisami, 1983; Timiras, 1988 for reviews of early and later studies). TH deficiency in human infants results in cretinism, which involves severe neurological defects and mental retardation.…”