RESUMO
This study investigated the neuroprotective effects of exendin-4 (EXE-4), an analog of the glucagon-like peptide 1 receptor (GLP-1R) on memory and on the neuronal populations that constitute the hippocampus of rats submitted to a sporadic dementia of Alzheimer's type (SDAT). Male Wistar rats received streptozotocin (STZ icv, 3 mg/kg diluted in aCFS, 5 µl/ventricle) and were treated for 21 days with EXE-4 (10 µg/kg, ip; saline as the vehicle). Four groups were formed: vehicle, EXE-4, STZ, and STZ + EXE-4. The groups were submitted to Y-Maze (YM), object recognition (ORT), and object displacement tasks (ODT) to assess learning and memory. The brains were used for immunohistochemical and immunofluorescent techniques with antibodies to NeuN, cleaved caspase-3 (CC3), PCNA, doublecortin (DCX), synaptophysin (SYP), and insulin receptor (IR). STZ worsened spatial memory in the YMT, as well as short-term (STM) and long-term (LTM) memories in the ORT and ODT, respectively. EXE-4 protected against memory impairment in STZ animals. STZ reduced mature neuron density (NeuN) and increased cell apoptosis (CC3) in the DG, CA1, and CA3. EXE-4 protected against neuronal death in all regions. EXE-4 increased PCNA+ cells in all regions of the hippocampus, and STZ attenuated this effect. STZ reduced neurogenesis in DG per se as well as synaptogenesis induced by EXE-4. EXE-4 increased immunoreactivity to IR in the CA1. From these findings, EXE-4 showed a beneficial effect on hippocampal pyramidal and granular neurons in the SDAT showing anti-apoptotic properties and promoting cell proliferation. In parallel, EXE-4 preserved the memory of SDAT rats. EXE-4 appears to enhance synapses at CA3 and DG. In conclusion, these data indicate that agonists to GLP-1R have a beneficial effect on hippocampal neurons in AD.
RESUMO
Chronic use of alcohol and tobacco cigarettes is associated to millions of deaths per year, either by direct or indirect causes. However, few studies have explored the additional risks of the combined use of these drugs. Here we assessed the effect of the combined use of alcohol and cigarette smoke on liver or kidney morphology, and on biochemical parameters in chronically treated rats. Male Wistar rats were allocated to receive 2 g/kg alcohol orally, which was followed by the inhalation of smoke from six cigarettes during 2 h (ALTB group) for 28 days. Other groups received alcohol alone (AL) or were exposed to cigarette smoke (TB) alone and were compared to control (CT) rats, which received water followed by ambient air. On day 29, rats were euthanized and blood samples were collected for aminotransferase enzymes (AST and ALT), creatinine, and urea analysis. Liver and kidney were weighted, dissected, fixed, and stained with hematoxylin and eosin for morphological analysis. Our results showed that necrosis was elevated in the AL, TB, and mainly the ALTB group in both liver and kidney of rats. Serum levels of AST and ALT were reduced by cigarette smoke exposure, independently of alcohol use. Serum creatinine levels increased after tobacco smoke exposure. On the other hand, TB and AL groups decreased serum urea levels, and their association restored that decrease. Absolute liver and kidney weights were lower in the cigarette smoke exposure rats. Lastly, body weight gain was lower in TB group and combined use restored it. Thus, we may infer that the use of alcohol, exposure to tobacco cigarette smoke or, mainly, their association promotes liver and kidney injuries, and this damage is related with biochemical changes in rats.