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Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease.
Chin Med J (Engl). 2008 Nov 20; 121(22):2320-3.CM

Abstract

BACKGROUND

Alzheimer disease (AD) is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system (RAS) play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme (ACE), and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD.

METHODS

Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups: control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein (A-beta) 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry.

RESULTS

Compared with the control group, the number of times needed to escape electrical stimuli increased (23.70 +/- 3.13, P < 0.001), the number of normal neurons in the CA1 region was reduced (density of 96.5 +/- 32.6/mm, P < 0.001), amyloid deposition was obvious, and ACE activity increased ((34.4 +/- 6.6) nmol x g(-1) x min(-1), P < 0.001) in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased (18.50 +/- 3.66, P < 0.001), the number of abnormal neurons increased (density of CA1 neurons was 180.8 +/- 28.5/mm, P < 0.001), amyloid deposition was reduced, and ACE activity was down-regulated ((26.2 +/- 6.2) nmol x g(-1) x min(-1), P < 0.001).

CONCLUSIONS

ACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity and delayed AD pathogenesis.

Authors+Show Affiliations

Department of Neurology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China. hou0718@xy3yy.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19080340

Citation

Hou, De-ren, et al. "Altered Angiotensin-converting Enzyme and Its Effects On the Brain in a Rat Model of Alzheimer Disease." Chinese Medical Journal, vol. 121, no. 22, 2008, pp. 2320-3.
Hou DR, Wang Y, Zhou L, et al. Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease. Chin Med J (Engl). 2008;121(22):2320-3.
Hou, D. R., Wang, Y., Zhou, L., Chen, K., Tian, Y., Song, Z., Bao, J., & Yang, Q. D. (2008). Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease. Chinese Medical Journal, 121(22), 2320-3.
Hou DR, et al. Altered Angiotensin-converting Enzyme and Its Effects On the Brain in a Rat Model of Alzheimer Disease. Chin Med J (Engl). 2008 Nov 20;121(22):2320-3. PubMed PMID: 19080340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease. AU - Hou,De-ren, AU - Wang,Yan, AU - Zhou,Lin, AU - Chen,Kun, AU - Tian,Yi, AU - Song,Zhi, AU - Bao,Juan, AU - Yang,Qi-dong, PY - 2008/12/17/entrez PY - 2008/12/17/pubmed PY - 2009/3/27/medline SP - 2320 EP - 3 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 121 IS - 22 N2 - BACKGROUND: Alzheimer disease (AD) is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system (RAS) play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme (ACE), and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD. METHODS: Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups: control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein (A-beta) 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry. RESULTS: Compared with the control group, the number of times needed to escape electrical stimuli increased (23.70 +/- 3.13, P < 0.001), the number of normal neurons in the CA1 region was reduced (density of 96.5 +/- 32.6/mm, P < 0.001), amyloid deposition was obvious, and ACE activity increased ((34.4 +/- 6.6) nmol x g(-1) x min(-1), P < 0.001) in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased (18.50 +/- 3.66, P < 0.001), the number of abnormal neurons increased (density of CA1 neurons was 180.8 +/- 28.5/mm, P < 0.001), amyloid deposition was reduced, and ACE activity was down-regulated ((26.2 +/- 6.2) nmol x g(-1) x min(-1), P < 0.001). CONCLUSIONS: ACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity and delayed AD pathogenesis. SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/19080340/Altered_angiotensin_converting_enzyme_and_its_effects_on_the_brain_in_a_rat_model_of_Alzheimer_disease_ L2 - https://Insights.ovid.com/pubmed?pmid=19080340 DB - PRIME DP - Unbound Medicine ER -