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Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice.

Durrant AR, Tamayev L, Anglister L - Front Mol Neurosci (2012)

Bottom Line: The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood.However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited.While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada, IMRIC, Faculty of Medicine, Hebrew University Medical School Jerusalem, Israel.

ABSTRACT
The cholinesterases, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) (pseudocholinesterase), are abundant in the nervous system and in other tissues. The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates AChE and BChE in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy (DMD) and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T) is a negative modulator of BChE, but not of AChE, in male mouse sera. T-removal elevated both BChE activity and the BChE/AChE ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

No MeSH data available.


Related in: MedlinePlus

Postnatal changes in body weight in male mice. The effect of strain on body weight is shown. Several litters of C57BL/10J (wt, ) and mdx (○) male mice were weighed over 3–21 weeks. Each data point is the mean ± SEM (n = 6–34). The dashed line at ~5 weeks marks initiation of puberty in the wt. *p < 0.05 between wt and mdx of the same age, showing that mdx mice gain less weight than wt during postnatal development but reach normal level by 11 weeks.
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Figure 1: Postnatal changes in body weight in male mice. The effect of strain on body weight is shown. Several litters of C57BL/10J (wt, ) and mdx (○) male mice were weighed over 3–21 weeks. Each data point is the mean ± SEM (n = 6–34). The dashed line at ~5 weeks marks initiation of puberty in the wt. *p < 0.05 between wt and mdx of the same age, showing that mdx mice gain less weight than wt during postnatal development but reach normal level by 11 weeks.

Mentions: Although the mdx mouse was reproductively competent (thus, T was present and functional), its postnatal growth was hindered compared to that of normal controls. The mdx mice displayed lower and more variable body weight compared to the controls, with the phenomenon being more pronounced in mdx females than in males (not shown). However, the body weight stabilized by 11 weeks of age at levels not significantly different from those of the control mice (Figure 1). The oscillatory shape of the curve was consistent with the finding that mdx mouse muscles undergo cycles of degeneration and regeneration until most muscles stabilize by 10 weeks (Settles et al., 1996). The mice we used were therefore aged 19–22 weeks, at which age their body weights are stable, and the majority of muscle fibers no longer display transient degeneration (Karpati et al., 1988).


Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice.

Durrant AR, Tamayev L, Anglister L - Front Mol Neurosci (2012)

Postnatal changes in body weight in male mice. The effect of strain on body weight is shown. Several litters of C57BL/10J (wt, ) and mdx (○) male mice were weighed over 3–21 weeks. Each data point is the mean ± SEM (n = 6–34). The dashed line at ~5 weeks marks initiation of puberty in the wt. *p < 0.05 between wt and mdx of the same age, showing that mdx mice gain less weight than wt during postnatal development but reach normal level by 11 weeks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378013&req=5

Figure 1: Postnatal changes in body weight in male mice. The effect of strain on body weight is shown. Several litters of C57BL/10J (wt, ) and mdx (○) male mice were weighed over 3–21 weeks. Each data point is the mean ± SEM (n = 6–34). The dashed line at ~5 weeks marks initiation of puberty in the wt. *p < 0.05 between wt and mdx of the same age, showing that mdx mice gain less weight than wt during postnatal development but reach normal level by 11 weeks.
Mentions: Although the mdx mouse was reproductively competent (thus, T was present and functional), its postnatal growth was hindered compared to that of normal controls. The mdx mice displayed lower and more variable body weight compared to the controls, with the phenomenon being more pronounced in mdx females than in males (not shown). However, the body weight stabilized by 11 weeks of age at levels not significantly different from those of the control mice (Figure 1). The oscillatory shape of the curve was consistent with the finding that mdx mouse muscles undergo cycles of degeneration and regeneration until most muscles stabilize by 10 weeks (Settles et al., 1996). The mice we used were therefore aged 19–22 weeks, at which age their body weights are stable, and the majority of muscle fibers no longer display transient degeneration (Karpati et al., 1988).

Bottom Line: The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood.However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited.While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada, IMRIC, Faculty of Medicine, Hebrew University Medical School Jerusalem, Israel.

ABSTRACT
The cholinesterases, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) (pseudocholinesterase), are abundant in the nervous system and in other tissues. The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates AChE and BChE in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy (DMD) and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T) is a negative modulator of BChE, but not of AChE, in male mouse sera. T-removal elevated both BChE activity and the BChE/AChE ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

No MeSH data available.


Related in: MedlinePlus