Tags

Type your tag names separated by a space and hit enter

Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of beta-secretase activation and beta-amyloid generation in rat brains.
Neuroscience 2009; 161(4):1045-56N

Abstract

We examined the effect of type 2 diabetes on stroke-induced Alzheimer's disease-like pathological and behavioral changes in rats. Rats were treated for 2 months with high fat diet (HFD) followed by streptozotocin (STZ) injection to induce type 2 diabetes (HFD-STZ model). Middle cerebral artery occlusion (MCAO) was used to induce cerebral focal ischemia. Animals were divided into four groups: Sham-NPD, Sham-HFD-STZ, MCAO-NPD and MCAO-HFD-STZ. The results showed that HFD-STZ treatment induced obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia, hyperglycemia and insulin resistance, characteristics of type 2 diabetes. The performance of rats in the Morris water maze test was impaired in MCAO-NPD and Sham-HFD-STZ rats, indicating cognitive deficits. Hippocampal caspase-3+ and beta amyloid (Abeta+) cell numbers, as well as beta-site amyloid precursor protein-cleaving enzyme (BACE1) levels and activity, increased in both groups. Moreover, HFD-STZ treatment exacerbated stroke-induced cognitive deficits, additively increased MCAO-induced activation of caspase-3, and increased levels of BACE1, C99 and Abeta. However, the level of insulin decreased in MCAO-HFD-STZ rats. These results suggested that type 2 diabetes deteriorated stroke-induced brain damage and cognitive impairment, which might be associated with increased Abeta generation and cytotoxicity. We concluded that type 2 diabetes exacerbated poststroke dementia possibly due to brain injury and synergistic generation of Abeta via activation of BACE1.

Authors+Show Affiliations

Department of Neurobiology, Institute of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 138 Yi-Xue-Yuan Road, Shanghai 200032, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19376202

Citation

Zhang, T, et al. "Exacerbation of Poststroke Dementia By Type 2 Diabetes Is Associated With Synergistic Increases of Beta-secretase Activation and Beta-amyloid Generation in Rat Brains." Neuroscience, vol. 161, no. 4, 2009, pp. 1045-56.
Zhang T, Pan BS, Zhao B, et al. Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of beta-secretase activation and beta-amyloid generation in rat brains. Neuroscience. 2009;161(4):1045-56.
Zhang, T., Pan, B. S., Zhao, B., Zhang, L. M., Huang, Y. L., & Sun, F. Y. (2009). Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of beta-secretase activation and beta-amyloid generation in rat brains. Neuroscience, 161(4), pp. 1045-56. doi:10.1016/j.neuroscience.2009.04.032.
Zhang T, et al. Exacerbation of Poststroke Dementia By Type 2 Diabetes Is Associated With Synergistic Increases of Beta-secretase Activation and Beta-amyloid Generation in Rat Brains. Neuroscience. 2009 Jul 21;161(4):1045-56. PubMed PMID: 19376202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of beta-secretase activation and beta-amyloid generation in rat brains. AU - Zhang,T, AU - Pan,B-S, AU - Zhao,B, AU - Zhang,L-M, AU - Huang,Y-L, AU - Sun,F-Y, Y1 - 2009/04/17/ PY - 2009/03/17/received PY - 2009/04/13/revised PY - 2009/04/13/accepted PY - 2009/4/21/entrez PY - 2009/4/21/pubmed PY - 2009/8/26/medline SP - 1045 EP - 56 JF - Neuroscience JO - Neuroscience VL - 161 IS - 4 N2 - We examined the effect of type 2 diabetes on stroke-induced Alzheimer's disease-like pathological and behavioral changes in rats. Rats were treated for 2 months with high fat diet (HFD) followed by streptozotocin (STZ) injection to induce type 2 diabetes (HFD-STZ model). Middle cerebral artery occlusion (MCAO) was used to induce cerebral focal ischemia. Animals were divided into four groups: Sham-NPD, Sham-HFD-STZ, MCAO-NPD and MCAO-HFD-STZ. The results showed that HFD-STZ treatment induced obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia, hyperglycemia and insulin resistance, characteristics of type 2 diabetes. The performance of rats in the Morris water maze test was impaired in MCAO-NPD and Sham-HFD-STZ rats, indicating cognitive deficits. Hippocampal caspase-3+ and beta amyloid (Abeta+) cell numbers, as well as beta-site amyloid precursor protein-cleaving enzyme (BACE1) levels and activity, increased in both groups. Moreover, HFD-STZ treatment exacerbated stroke-induced cognitive deficits, additively increased MCAO-induced activation of caspase-3, and increased levels of BACE1, C99 and Abeta. However, the level of insulin decreased in MCAO-HFD-STZ rats. These results suggested that type 2 diabetes deteriorated stroke-induced brain damage and cognitive impairment, which might be associated with increased Abeta generation and cytotoxicity. We concluded that type 2 diabetes exacerbated poststroke dementia possibly due to brain injury and synergistic generation of Abeta via activation of BACE1. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19376202/Exacerbation_of_poststroke_dementia_by_type_2_diabetes_is_associated_with_synergistic_increases_of_beta_secretase_activation_and_beta_amyloid_generation_in_rat_brains_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)00639-3 DB - PRIME DP - Unbound Medicine ER -