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Effects of hypothyroidism on expression of CRMP2B and ARPC5 during development of the rat frontal cortex.

Liu CR, Miao J, Zhang YL, Liu YM, Yu BG - Int. J. Biol. Sci. (2013)

Bottom Line: Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression.Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5.These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China. lcr68@163.com

ABSTRACT
Congenital hypothyroidism (CH) can lead to irreversible central nervous system (CNS) damage. However, the pathogenesis of the developmental brain disorders caused by CH has not been completely elucidated. ARPC5 and CRMP2 are closely associated with neurite outgrowth in brain development. Thus, the aim of the present study was to determine whether CRMP2B and ARPC5 expression is altered in the developing cerebral cortex of rats with CH. Control rats and rats with hypothyroidism were sacrificed at birth and at 15 days postpartum. We performed qRT-PCR to detect differences in the crmp2B and arpc5 mRNA expression in the right half of the frontal cortex of these rats. Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression. Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5. Results showed increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism. These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B. CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization.

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Representative immunohistochemical staining for CRMP2B protein expression in the cortical layer III and IV of control rats and hypothyroidism rats during development, 400×. (a): P1 control, CRMP2B staining was scattered and predominantly distributed in neurites and the cytoplasm of neurons (⇒ red). (b): P1 hypothyroidism, the distribution and cellular location were similar to P1 control group. (c): P15 control, majority of CRMP2B staining cells are cytoplasmic staining cells with longer neurite (⇒ red). (d): P15 hypothyroidism. majority of CRMP2B staining cells are nuclear staining cells with shorter neurite(⇒ red).
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Figure 3: Representative immunohistochemical staining for CRMP2B protein expression in the cortical layer III and IV of control rats and hypothyroidism rats during development, 400×. (a): P1 control, CRMP2B staining was scattered and predominantly distributed in neurites and the cytoplasm of neurons (⇒ red). (b): P1 hypothyroidism, the distribution and cellular location were similar to P1 control group. (c): P15 control, majority of CRMP2B staining cells are cytoplasmic staining cells with longer neurite (⇒ red). (d): P15 hypothyroidism. majority of CRMP2B staining cells are nuclear staining cells with shorter neurite(⇒ red).

Mentions: CRMP2B staining was scattered throughout the frontal cortex of P1 rats. CRMP2B was predominantly distributed in neurites and the cytoplasm of neurons. No difference was observed between the intensity of CRMP2B staining in control rats and rats with hypothyroidism at this stage (Z = -0.968, P = 0.333) (Table 2). CRMP2B was expressed diffusely throughout the six layers of frontal cortex of P15 rats, and was expressed in the nucleus and cytoplasm of neurons, as well as in neurites. Cortical layer III and IV were emphatically studied. The intensity of CRMP2B staining was stronger in control rats than in rats with hypothyroidism at P15 (Z = -2.031, P = 0.042) (Table 3). However, the number of CRMP2B-positive nuclei was greater in rats with hypothyroidism compared with control rats at this stage (t = 19.359, P < 0.001) (Table 6). Diminished dendritic branching and elongation was observed in neurons with intense nuclear CRMP2B staining (t=-7.364, P<0.001) (Fig.3).


Effects of hypothyroidism on expression of CRMP2B and ARPC5 during development of the rat frontal cortex.

Liu CR, Miao J, Zhang YL, Liu YM, Yu BG - Int. J. Biol. Sci. (2013)

Representative immunohistochemical staining for CRMP2B protein expression in the cortical layer III and IV of control rats and hypothyroidism rats during development, 400×. (a): P1 control, CRMP2B staining was scattered and predominantly distributed in neurites and the cytoplasm of neurons (⇒ red). (b): P1 hypothyroidism, the distribution and cellular location were similar to P1 control group. (c): P15 control, majority of CRMP2B staining cells are cytoplasmic staining cells with longer neurite (⇒ red). (d): P15 hypothyroidism. majority of CRMP2B staining cells are nuclear staining cells with shorter neurite(⇒ red).
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Figure 3: Representative immunohistochemical staining for CRMP2B protein expression in the cortical layer III and IV of control rats and hypothyroidism rats during development, 400×. (a): P1 control, CRMP2B staining was scattered and predominantly distributed in neurites and the cytoplasm of neurons (⇒ red). (b): P1 hypothyroidism, the distribution and cellular location were similar to P1 control group. (c): P15 control, majority of CRMP2B staining cells are cytoplasmic staining cells with longer neurite (⇒ red). (d): P15 hypothyroidism. majority of CRMP2B staining cells are nuclear staining cells with shorter neurite(⇒ red).
Mentions: CRMP2B staining was scattered throughout the frontal cortex of P1 rats. CRMP2B was predominantly distributed in neurites and the cytoplasm of neurons. No difference was observed between the intensity of CRMP2B staining in control rats and rats with hypothyroidism at this stage (Z = -0.968, P = 0.333) (Table 2). CRMP2B was expressed diffusely throughout the six layers of frontal cortex of P15 rats, and was expressed in the nucleus and cytoplasm of neurons, as well as in neurites. Cortical layer III and IV were emphatically studied. The intensity of CRMP2B staining was stronger in control rats than in rats with hypothyroidism at P15 (Z = -2.031, P = 0.042) (Table 3). However, the number of CRMP2B-positive nuclei was greater in rats with hypothyroidism compared with control rats at this stage (t = 19.359, P < 0.001) (Table 6). Diminished dendritic branching and elongation was observed in neurons with intense nuclear CRMP2B staining (t=-7.364, P<0.001) (Fig.3).

Bottom Line: Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression.Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5.These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China. lcr68@163.com

ABSTRACT
Congenital hypothyroidism (CH) can lead to irreversible central nervous system (CNS) damage. However, the pathogenesis of the developmental brain disorders caused by CH has not been completely elucidated. ARPC5 and CRMP2 are closely associated with neurite outgrowth in brain development. Thus, the aim of the present study was to determine whether CRMP2B and ARPC5 expression is altered in the developing cerebral cortex of rats with CH. Control rats and rats with hypothyroidism were sacrificed at birth and at 15 days postpartum. We performed qRT-PCR to detect differences in the crmp2B and arpc5 mRNA expression in the right half of the frontal cortex of these rats. Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression. Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5. Results showed increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism. These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B. CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization.

Show MeSH
Related in: MedlinePlus