Exenatide is a potent and selective agonist for the GLP-1 (glucagon-like peptide-1) receptor. Recent studies are focused on the effects of GLP-1 analogues on hippocampal neurogenesis, cognition, learning and memory functions. The aim of this study was to assess the effects of chronic exenatide treatment (0.1 μg/kg, s.c, twice daily for 2 weeks) on spatial memory functions by using the modified elevated plus maze (mEPM) test and emotional memory functions by using the passive avoidance (PA) test in streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice. As the genes involved in neurite remodelling are among the primary targets of regulation, the effects of diabetes and chronic administration of exenatide on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus of mice were also determined using quantitative real-time polymerase chain reaction (RT-PCR). This study revealed that in the mEPM and PA tests, type-2 diabetes-induced mice exhibited significant impairment of learning and memory which were ameliorated by GLP-1 receptor agonist exenatide. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in diabetic mice, and these alterations were increased by exenatide treatment. Since, exenatide improves cognitive ability in STZ/NA-induced diabetic mice and activates molecular mechanisms of memory storage in response to a learning experience, it may be a candidate for alleviation of mood and cognitive disorder.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has modulating effects on insulin release. GLP-1 and receptors for GLP-1 are widely expressed throughout the body including the brain. The expression of GLP-1 receptors is very specific to large neurons in hippocampus, neocortex, and cerebellum. GLP-1 receptor stimulation enhances glucose-dependent insulin secretion and lowers blood glucose in type 2 diabetes mellitus. Studies on adipobiology of neurotrophins have focused on nerve growth factor (NGF) as an example of adipose-derived neurotrophins. Compromised trophic factor signaling may underlie neurodegenerative diseases ranging from Alzheimer's disease to diabetic neuropathies. Exenatide, a potent and selective agonist for the GLP-1 receptor, is currently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to assess the effect of chronic exenatide treatment on the hippocampal gene expression levels of GLP-1 receptor and NGF in diabetic mice. The effects of chronic exenatide treatment (0.1 μg/kg, s.c., twice daily for 2 weeks) on GLP-1 receptor and NGF gene expression levels in the hippocampus of streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice were assessed by quantitative real-time polymerase chain reaction (RT-PCR). The results of this study revealed that hippocampal gene expression of GLP-1 receptor and NGF were downregulated in diabetic mice. Importantly, a significant increase in the gene expression level of GLP-1 receptor and NGF was determined after 2 weeks of exenatide administration. Increased gene expression level of GLP-1 receptor and NGF may underlie the beneficial action of exenatide in STZ/NA-induced diabetes.

The goal of this study was to determine the distribution of left ventricular (LV) systolic and diastolic dysfunctions and their prognostic value in canine parvovirus-infected dogs suffering from severe sepsis and septic shock (SS/SS). Twenty dogs with SS/SS (experimental group) and 18 healthy dogs (control group) were used in the study. Systolic and diastolic dysfunction was present in three (15%) and 14 (70%) diseased dogs, respectively, with both types of dysfunction present in two (10%) of the patients. These dogs were split into two groups: survivors (Sv, n = 14) and non-survivors (non-Sv, n = 6). The pulsed wave tissue Doppler (PW-TDI) septal mitral annulus systolic velocity (LVS'), an index of systolic dysfunction, had a high sensitivity and specificity to differentiate Sv and non-Sv animals, with values of 83.3% (95% CI: 41.6–98.4) and 83.3% (95% CI: 59.8–94.8), respectively, at an optimum cut-off point of ≥ 9.90. The PW-TDI septal early mitral annulus early-diastolic peak velocity (E'), an index of diastolic dysfunction, had the best sensitivity and specificity to differentiate Sv and non-Sv dogs, with values of 100% (95% CI: 55.2–100) and 100% (95% CI: 78.9–100), respectively, at an optimum cut-off point of ≤ 6.50. Therefore, diastolic dysfunction determined by E' is a good independent outcome predictor.

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This study was performed to evaluate the end-systolic wall stress/end-systolic volume index ratio (ESWS/ESV-I) for LV systolic function in Anatolian shepherd dogs (ASHs) with stage B2 degenerative mitral valve disease (DMVD). Thirty-eight adult ASHs with DMVD (experimental group; 20 B1 dogs and 18 B2 dogs) and 30 weight-matched adult healthy ASHs (control group) were used as subjects. There was no overlap for the ESWS/ESV-I ratio (0.83±0.03, range: 0.61-1.09 for B2 dogs, 1.34±0.05, range: 1.11-1.89 for B1 dogs, 2.17±0.0 range: 1.91-3.02 for the control dogs) among the groups. ESWS/ESV-I ratio (≤1.09) in ASHs with stage B2 DMVD may play a developmental role in left ventricular remodelling and risk factor for development of systolic dysfunction.