Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat

Abstract

Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for γ-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1β and TNF-α) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE.

Keywords: acetylcholine (ACh); acetylcholinesterase (AChE); acide γ-aminobutirique (GABA); acétylcholine (ACh); acétylcholinestérase (AChE); cognitive dysfunction; diabetic encephalopathy (DE); dysfonction cognitive; encéphalopathie diabétique (ED); glutamate (Glu); glutamate decarboxylase (GAD); glutamate décarboxylase (GAD); neuro-inflammation; neuroinflammation; neurotransmetteur; neurotransmitter; γ-aminobutyric acid (GABA).