TY  - JOUR
A1  - Yuliani, Tri
A1  - Lobentanzer, Sebastian
A1  - Klein, Jochen
T1  - Central cholinergic function and metabolic changes in streptozotocin‐induced rat brain injury
T2  - Journal of neurochemistry
N2  - As glucose hypometabolism in the brain is an early sign of Alzheimer´s dementia (AD), the diabetogenic drug streptozotocin (STZ) has been used to induce Alzheimer‐like pathology in rat brain by intracereboventricular injection (icv‐STZ). However, many details of the pathological mechanism of STZ in this AD model remain unclear. Here, we report metabolic and cholinergic effects of icv‐STZ using microdialysis in freely moving animals. We found that icv‐STZ at a dose of 3 mg/kg (2 × 1.5 mg/kg) causes overt toxicity reflected in body weight loss. Three weeks after STZ administration, histological examination revealed a high number of glial fibrillary acidic protein reactive cells in the hippocampus, accompanied by Fluoro‐Jade C‐positive cells in the CA1 region. Glucose and lactate levels in microdialysates were unchanged, but mitochondrial respiration measured ex vivo was reduced by 9%–15%. High‐affinity choline uptake, choline acetyltransferase, and acetylcholine esterase (AChE) activities in the hippocampus were reduced by 16%, 28%, and 30%, respectively. Importantly, extracellular acetylcholine (ACh) levels in the hippocampus were unchanged and responded to behavioral and pharmacological challenges. In comparison, extracellular ACh levels and cholinergic parameters in the striatum were unchanged or slightly increased. We conclude that the icv‐STZ model poorly reflects central cholinergic dysfunction, an important characteristic of dementia. The icv‐STZ model may be more aptly described as an animal model of hippocampal gliosis.
KW  - acetylcholine
KW  - Alzheimer's disease
KW  - astrogliosis
KW  - complex IV
KW  - glucose
KW  - hippocampus
KW  - lactate
KW  - microdialysis
KW  - mitochondrial respiration
KW  - streptozotocin
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56513
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-565135
SN  - 1471-4159
VL  - 2020
PB  - Wiley-Blackwell
CY  - Oxford
ER  -