Limits...
Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer's drug candidates.

Gao Y, Hu YZ, Li RS, Han ZT, Geng Y, Xia Z, Du WJ, Liu LX, Zhang HH, Wang LN - Neuropsychiatr Dis Treat (2015)

Bottom Line: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice.CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde.Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, Beijing, People's Republic of China.

ABSTRACT

Background: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.

Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.

Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1(+) activated microglia in the cortex of the APP/PS1 mice.

Conclusion: Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

No MeSH data available.


Related in: MedlinePlus

Effects of CEGI on the neuronal morphology and expression of Bcl-2 family members in the CA1 region of the hippocampus in APP/PS1 mice.Notes: *P<0.05, **P<0.01 compared with the nontransgenic (nTg) group; #P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A–E) Hematoxylin and eosin staining. The neurons in the brains of nTg mice were found to be intact and well arranged. On the other hand, the neurons in the Tg mice exhibited shrunken and triangulated neuronal bodies (black arrows). The cells were disordered, with a slightly changed cell polarity. Treatment with CEGI or donepezil diminished the shrunken and triangulated neurons (black arrows) in the hippocampal CA1, and the neurons recovered their characteristic shape and arrangement, similar to the nTg mice; however, an enlarged extracellular gap was detected. (F–J) Immunohistochemical staining for Bcl-2. (K–O) Immunohistochemical staining for Bax. Scale bar 50 μm. (P) Statistical graph displaying the mean optical density of Bcl-2; (Q) statistical graph displaying the mean optical density of Bax; (R) a statistical graph displaying the ratio of Bcl-2/Bax. Data presented as means ± SE, n=7–8 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4356454&req=5

f4-ndt-11-537: Effects of CEGI on the neuronal morphology and expression of Bcl-2 family members in the CA1 region of the hippocampus in APP/PS1 mice.Notes: *P<0.05, **P<0.01 compared with the nontransgenic (nTg) group; #P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A–E) Hematoxylin and eosin staining. The neurons in the brains of nTg mice were found to be intact and well arranged. On the other hand, the neurons in the Tg mice exhibited shrunken and triangulated neuronal bodies (black arrows). The cells were disordered, with a slightly changed cell polarity. Treatment with CEGI or donepezil diminished the shrunken and triangulated neurons (black arrows) in the hippocampal CA1, and the neurons recovered their characteristic shape and arrangement, similar to the nTg mice; however, an enlarged extracellular gap was detected. (F–J) Immunohistochemical staining for Bcl-2. (K–O) Immunohistochemical staining for Bax. Scale bar 50 μm. (P) Statistical graph displaying the mean optical density of Bcl-2; (Q) statistical graph displaying the mean optical density of Bax; (R) a statistical graph displaying the ratio of Bcl-2/Bax. Data presented as means ± SE, n=7–8 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.

Mentions: As shown in Figure 4, there were no significant differences in cholinergic measures (AChE and ChAT) among the five different groups. However, mice from the CEGI-L and donepezil groups (especially the donepezil group) showed slightly lower AChE (Figure 3C) and slightly higher ChAT compared to Tg mice (Figure 3D).


Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer's drug candidates.

Gao Y, Hu YZ, Li RS, Han ZT, Geng Y, Xia Z, Du WJ, Liu LX, Zhang HH, Wang LN - Neuropsychiatr Dis Treat (2015)

Effects of CEGI on the neuronal morphology and expression of Bcl-2 family members in the CA1 region of the hippocampus in APP/PS1 mice.Notes: *P<0.05, **P<0.01 compared with the nontransgenic (nTg) group; #P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A–E) Hematoxylin and eosin staining. The neurons in the brains of nTg mice were found to be intact and well arranged. On the other hand, the neurons in the Tg mice exhibited shrunken and triangulated neuronal bodies (black arrows). The cells were disordered, with a slightly changed cell polarity. Treatment with CEGI or donepezil diminished the shrunken and triangulated neurons (black arrows) in the hippocampal CA1, and the neurons recovered their characteristic shape and arrangement, similar to the nTg mice; however, an enlarged extracellular gap was detected. (F–J) Immunohistochemical staining for Bcl-2. (K–O) Immunohistochemical staining for Bax. Scale bar 50 μm. (P) Statistical graph displaying the mean optical density of Bcl-2; (Q) statistical graph displaying the mean optical density of Bax; (R) a statistical graph displaying the ratio of Bcl-2/Bax. Data presented as means ± SE, n=7–8 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356454&req=5

f4-ndt-11-537: Effects of CEGI on the neuronal morphology and expression of Bcl-2 family members in the CA1 region of the hippocampus in APP/PS1 mice.Notes: *P<0.05, **P<0.01 compared with the nontransgenic (nTg) group; #P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A–E) Hematoxylin and eosin staining. The neurons in the brains of nTg mice were found to be intact and well arranged. On the other hand, the neurons in the Tg mice exhibited shrunken and triangulated neuronal bodies (black arrows). The cells were disordered, with a slightly changed cell polarity. Treatment with CEGI or donepezil diminished the shrunken and triangulated neurons (black arrows) in the hippocampal CA1, and the neurons recovered their characteristic shape and arrangement, similar to the nTg mice; however, an enlarged extracellular gap was detected. (F–J) Immunohistochemical staining for Bcl-2. (K–O) Immunohistochemical staining for Bax. Scale bar 50 μm. (P) Statistical graph displaying the mean optical density of Bcl-2; (Q) statistical graph displaying the mean optical density of Bax; (R) a statistical graph displaying the ratio of Bcl-2/Bax. Data presented as means ± SE, n=7–8 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.
Mentions: As shown in Figure 4, there were no significant differences in cholinergic measures (AChE and ChAT) among the five different groups. However, mice from the CEGI-L and donepezil groups (especially the donepezil group) showed slightly lower AChE (Figure 3C) and slightly higher ChAT compared to Tg mice (Figure 3D).

Bottom Line: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice.CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde.Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, Beijing, People's Republic of China.

ABSTRACT

Background: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.

Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.

Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1(+) activated microglia in the cortex of the APP/PS1 mice.

Conclusion: Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

No MeSH data available.


Related in: MedlinePlus