Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain

Desouza, Lynette A.; Ladiwala, Uma; Daniel, Sarah M.; Agashe, Shubhada; Vaidya, Rama; Vaidya, Vidita A.

doi:10.1016/j.mcn.2005.03.010

Cited by 206 publications

(211 citation statements)

References 52 publications

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“…The effect of TH deficiency on the DCX population most probably reflects an impaired generation of neuronal progenitors since it was similar to that on proliferation, whether hormone insufficiency was maintained for 20 or 45 days. In contrast to other studies, 27,28 we did not observe changes in cell survival in the different experimental situations, as assessed by three different methods: number of pyknotic nuclei, TUNEL staining, and cleaved caspase-3-immunopositive cells. Therefore, selective apoptosis can be discarded in our studies.…”

Section: Discussioncontrasting

confidence: 99%

“…Uchida et al 53 also found that TH increased cell proliferation in the hippocampus of hypothyroid mice. In contrast, Desouza et al 27 and Ambrogini et al 28 found no effect of TH on cell proliferation as measured by BrdU incorporation. The reasons for these discrepancies are not apparent to us, but may reside in different BrdU uptake protocols or to the use of goitrogens to induce hypothyroidism.…”

Section: Discussionmentioning

confidence: 90%

“…[20][21][22] TH action is mediated through T3 nuclear receptors, and T3 receptor deficiency or mutations also alter adult hippocampal structure and hippocampus-dependent behavior. 23,24 Very recently, TH have been implicated in adult neurogenesis, [25][26][27][28] but little is known on the functional consequences of TH actions on proliferation of neuronal progenitors.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

et al. 2006

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Hormonal imbalances are involved in many of the age-related pathologies, as neurodegenerative and psychiatric diseases. Specifically, thyroid state alterations in the adult are related to psychological changes and mood disorders as depression. The dentate gyrus of the hippocampal formation undergoes neurogenesis in adult mammals including humans. Recent evidence suggests that depressive disorders and their treatment are tightly related to the number of newly born neurons in the dentate gyrus. We have studied the effect of thyroid hormones (TH) on hippocampal neurogenesis in adult rats in vivo. A short period of adultonset hypothyroidism impaired normal neurogenesis in the subgranular zone of the dentate gyrus with a 30% reduction in the number of proliferating cells. Hypothyroidism also reduced the number of newborn neuroblasts and immature neurons (doublecortin (DCX) immunopositive cells) which had a severely hypoplastic dendritic arborization. To correlate these changes with hippocampal function, we subjected the rats to the forced swimming and novel object recognition tests. Hypothyroid rats showed normal memory in object recognition, but displayed abnormal behavior in the forced swimming test, indicating a depressive-like disorder. Chronic treatment of hypothyroid rats with TH not only normalized the abnormal behavior but also restored the number of proliferative and DCX-positive cells, and induced growth of their dendritic trees. Therefore, hypothyroidism induced a reversible depressive-like disorder, which correlated to changes in neurogenesis. Our results indicate that TH are essential for adult hippocampal neurogenesis and suggest that mood disorders related to adult-onset hypothyroidism in humans could be due, in part, to impaired neurogenesis.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

et al. 2006

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“…One mechanism which may explain the accelerated growth of hippocampal formation in the recovery animals may be increased neurogenesis which is known to occur in the postnatal and adult HC; indeed there is evidence that this proliferation is stimulated by thyroid hormones and retarded in their absence (Ambrogini et al, 2005;Desouza et al, 2005;Uchida et al, 2005). However, active neuronal proliferation is mainly restricted to the dentate gyrus of the hippocamus and is known to occur in the HC proper where our results were obtained.…”

Section: Prospects For Rehabilitation From Hypothyroid Brain Retardationmentioning

confidence: 49%

“…A few previous studies investigated the deleterious effects of thyroid hormone deficiency on the developing hippocampus (HC) (Gould, et al 1991,Lauder & Mugnaini, 1977,1980Rabie et al, 1979;Rami & Rabie, 1988;Rami et al, 1986a,b). Recently several molecular and functional studies have also appeared (Alvarez- Dolado et al, 2001;Alzoubi et al, 2005;Ambrogini et al, 2005;Desouza et al, 2005;Dong et al, 2005;Gerges & Alkadhi, 2004,Gilbert, 2004Gilbert & Paczkowski, 2003;Martinez et al, 2001;Matos, et al 2002;Meaney et al, 2000;Roskoden et al, 1999;Sui & Gilbert, 2003;Uchida et al, 2005;Vaidya et al, 2001;Vara et al, 2002Vara et al, ,2003.…”

Section: Introductionmentioning

confidence: 99%

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

Farahvar

Meisami

2007

Experimental Neurology

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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.

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Stress and Coping

McEwen

2009

Handbook of Neuroscience for the Behavioral Sciences

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Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain

Cited by 206 publications

References 52 publications

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

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

Stress and Coping

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