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. 2016 Jun 1:16:159.
doi: 10.1186/s12906-016-1144-7.

Herbal formula GAPT prevents beta amyloid deposition induced Ca(2+)/Calmodulin-dependent protein kinase II and Ca(2+)/Calmodulin-dependent protein phosphatase 2B imbalance in APPV717I mice

Jing Shi  1 , Xuekai Zhang  1 , Long Yin  1 , Mingqing Wei  1 , Jingnian Ni  1 , Ting Li  1 , Pengwen Wang  2 , Jinzhou Tian  3 , Yongyan Wang  4
Affiliations

Herbal formula GAPT prevents beta amyloid deposition induced Ca(2+)/Calmodulin-dependent protein kinase II and Ca(2+)/Calmodulin-dependent protein phosphatase 2B imbalance in APPV717I mice

Jing Shi et al. BMC Complement Altern Med. .

Retraction in

Abstract

Background: Synaptic dysfunction is one of the pathological characteristics of Alzheimer's disease (AD), which is directly related to the progressive decline of cognitive function. CaMKII and CaN have been found to play important roles in memory processes and synaptic transmission. So present study aimed to elucidate relationships between CaMKII, CaN and cognitive decline in APPV717I mice, and to reveal whether the cognitive improving effects of GAPT is conducted through rebalance CaMKII and CaN.

Methods: Three-month-old-male APPV717I mice were randomly divided into ten groups (n = 12 per group) and received intragastrically administrated vehicle, donepezil or different doses of herbal formula GAPT for 8 or 4 months. Three-month-old male C57BL/6 J mice was set as vehicle control.

Results: Immunohistochemistry analysis showed that there were CaMKII expression decrease in the CA1 region of APPV717I transgenic mice, while the CaMKII expression of donepezil or GAPT treated transgenic mice were all increased. And there were CaN expression increase in the brain cortex of APPV717I transgenic mice, while there were decrease of CaN expression in donepezil or GAPT treated transgenic group. Western blot analysis showed the similar expression pattern without significant difference.

Conclusion: GAPT extract have showed effectiveness in activating the expression of CaMKII and inhibiting the expression of CaN either before or after the formation of amyloid plaques in the brain of APPV717I transgenic mice, which may in certain way alleviated neuron synaptic dysfunction in AD.

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Figures

Fig. 1
Fig. 1
Expression of CaMK II (Average OD) in hippocampal CA1 region in the experimental mice at the age of 7 months old were measured by immunohistochemistry staining. Note:▲ p < 0.05,vs control group, *p < 0.05,vs model group, ANOVA. CaMK II expression was determined by immunohistochemistry in the hippocampus of experimental mice. Data are expressed as mean ± SD (Average OD) of the CaMK II positive neuronal area (anti-body for CaMK II, 1:1000). Control: C57BL/6 J mice; APP: APPV717I mice; APP + D: donepezil; APP + Gl: GAPT low dose; APP + Gm: GAPT middle dose; APP + Gh: GAPT high dose
Fig. 2
Fig. 2
Expression of CaN (Average OD) in hippocampal CA1 region in the experimental mice at the age of 7 months old were measured by immunohistochemistry staining. Note: ▲ p < 0.05,vs control group, ANOVA. CaN expression was determined by immunohistochemistry in the hippocampus of experimental mice. Data are expressed as mean ± SD (Average OD) of the CaN positive neuronal area (anti-body for CaN, 1:100). Control: C57BL/6 J mice; APP: APPV717I mice; APP + D: donepezil; APP + Gl: GAPT low dose; APP + Gm: GAPT middle dose; APP + Gh: GAPT high dose
Fig. 3
Fig. 3
Expression of CaMKII, CaN in hippocampus tissue homogenates of experimental mice at the age of 7 months were determined by western-blotting. Notes: Control: C57BL/6 J mice; APP: APPV717I mice; APP + D: donepezil; APP + Gl: GAPT low dose; APP + Gm: GAPT middle dose; APP + Gh: GAPT high dose. There was no significant difference between each group in both CaMKII, CaN
Fig. 4
Fig. 4
Expression of CaMKII (Average OD) in hippocampal CA1 region in the experimental mice at the age of 11 months old were measured by immunohistochemistry staining. Notes:▲ p < 0.05, ▲▲ p < 0.01,vs control group, *p < 0.05, **p < 0.01,vs model group, ANOVA. Control: C57BL/6 J mice; APP: APPV717I mice; APP + D: donepezil; APP + Gl: GAPT low dose; APP + Gm: GAPT middle dose; APP + Gh: GAPT high dose. CaMKII expression was determined by immunohistochemistry in the hippocampus of experimental mice. Data are expressed as mean ± SD (Average OD) of the CaMKII positive neuronal area (anti-body for CaMKII, 1:1000)
Fig. 5
Fig. 5
Expression of CaN (Average OD) in hippocampal CA1 region in the experimental mice at the age of 11 months old were measured by immunohistochemistry staining. Notes:▲ P < 0.05, ▲▲ P < 0.01, vs Control group, *P < 0.05,vs model group, ANOVA. Control: C57BL/6 J mice; APP: APPV717I mice; APP + D: donepezil; APP + Gl: GAPT low dose; APP + Gm: GAPT middle dose; APP + Gh: GAPT high dose. CaN expression was determined by immunohistochemistry in the hippocampus of experimental mice. Data are expressed as mean ± SD (Average OD) of the CaN positive neuronal area (anti-body for CaN, 1:100)
Fig. 6
Fig. 6
Expression of CaMKII, CaN in hippocampus tissue homogenates of experimental mice at the age of 11 months were determined by western-blotting. Notes: Control: C57BL/6 J mice; APP: APPV717I mice; D: donepezil; Gl: GAPT low dose; APP + Gm: GAPT middle dose; APP + Gh: GAPT high dose. There was no significant difference in the expression of CaMKII and CaN between each group
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