Induction of bacterial cystitis in female rabbits by uropathogenic Escherichia coli and the differences between the bladder dome and trigone.

This study is designed to evaluate the histological effects of uropathogenic Escherichia coli (UPEC) infection in the urinary bladder of female rabbits and compare the differences between the dome and trigone. Bacterial cystitis was induced in 13 female rabbits by transurethral inoculation of UPEC into the urinary bladder. Eight animals served as controls. Urine samples were collected by catheterization and cultured for bacterial growth after 12 and 24 hours then every 48 hours. Infection was defined as ≥(1X105) colony-forming unit/ml of UPEC in the first two urine samples. Bladder dome and trigonal specimens were examined by light and scanning electron microscopy eight days after infection. There was a sustained increase in bacterial count, with urethral bleeding and rabbit weakness suggesting bladder colonization in the 10/13 study group (77%). Infection was not demonstrated in two animals and was spontaneously cleared in the third after 48 hours. No control animals developed an infection. In infected rabbits (n = 10), the dome showed inflammatory changes including the epithelial loss or thinning, inflammatory cell infiltration, and congested blood vessels compared to controls. The trigone showed a more pronounced inflammatory response than the dome. The presence of urinary bacterial growth, infection manifestations, and inflammatory changes that were more severe in the trigone than in the dome indicate successful bacterial inoculation and induction of cystitis. This animal model can be used for clinical trials on female cystitis. Our histological findings support a possible role of trigone in the pathogenesis of urinary tract infection.

Analyzing the impact of sleep duration on atrial fibrillation risk: a comprehensive systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested an association between sleep duration and cardiovascular diseases; however, the link to AF is inconclusive. This study aimed to explore the relationship between sleep duration and AF by conducting a systematic review and meta-analysis of primary studies to provide evidence of the link between insufficient sleep and AF. METHODS: A review of the existing literature was conducted to identify the primary studies that examined the association between AF and sleep duration. The inquiry spanned databases, including PubMed, Embase, MEDLINE, and Google Scholar, from their inception through October 2023. RESULTS: Meta-analysis revealed a statistically significant association (p < 0.01) between shorter sleep duration and the incidence of AF (hazard ratio (HR), 1.18; 95% CI, 1.03-1.34; I2 = 89%). Conversely, longer sleep duration did not exhibit a statistically significant association with the incidence of AF (HR, 1.03; 95% CI, 0.92-1.14; I2 = 66%, p = 0.02). The sensitivity analysis demonstrated reduced heterogeneity after excluding specific studies. CONCLUSION: Insufficient sleep duration was associated with an increased risk of AF, whereas a longer sleep duration did not show a significant correlation. Standardized methods for sleep assessment and AF diagnosis as well as adjustments for confounding factors are suggested for future studies to improve the clarity and understanding of these associations.

Hyperinsulinemia in rats causes impairment of spatial memory and learning with defects in hippocampal synaptic plasticity by involvement of postsynaptic mechanisms.

In addition to its peripheral metabolic functions, insulin acts as a central neuromodulator and affects synaptic plasticity of the hippocampal neurons. In this study, hyperinsulinemic obese zucker rats (OZR) with autosomal recessive mutation of the fa-gene were tested in water maze for learning and memory. The animals were then decapitated and hippocampal slices were prepared for electrophysiological examination. In the water maze test, the OZR performed less efficient than their counter lean control rats (LCR). The OZR showed prolonged latency and increased distance swam to reach a hidden platform. In the electrophysiological experiments, the hippocampal slices were examined for paired-pulse facilitation (PPF), long-term potentiation (LTP), and depression expression. The results showed that while the PPF (thus mainly the presynaptic mechanisms) was not affected, the LTP expression (169.9 ± 16.6 vs. 310.7 ± 2.4 %) and the synaptic plasticity range (69.2 vs. 211.2 %) were both reduced in the OZR animals compared to the LCR. It is concluded that hyperinsulinemia in the OZR resulted in defects in hippocampal synaptic plasticity associated with deterioration in spatial learning and memory functions.

The Effect of High-Dose Methyl Vitamin B12 Therapy on Epileptogenesis in Rats: An In Vivo Study.

Introduction Epileptogenesis has been considered one of the most prevalent diseases affecting significant numbers of individuals worldwide. Since vitamin B12 has been reported to possess antiepileptic effects, this supports that vitamin B12 deficiency is correlated to seizure occurrence. Hence, this study aimed to evaluate the neuroprotective effects of vitamin B12 injection on pentylenetetrazole (PTZ)-induced rats. Methods The study was performed using 40 adult female Sprague-Dawley rats (~250 g). A 45 mg/kg PTZ was intraperitoneally injected into rat models to induce seizure effects. Different groups of rat models received methyl vitamin B12 therapy at different dosages, a low dosage of 45 µg/kg and a high dosage of 85 µg/kg, at different pre-treatment periods, one day and two weeks prior to PTZ injection. A control group, which received only PTZ injection, served as a reference. The seizure latency, seizure intensity, and differences in the quality of seizures and their characteristics, from simple twitches to complete seizures, were observed after 30 minutes of PTZ injection. Results In general, the latency to convulsion significantly increased when vitamin B12 pre-treatment was employed. The longest latency time (LT) of 520.63±73.83 seconds was observed when a high dosage of vitamin B12 at 85 µg/kg was injected one day prior to PTZ inoculation, which was significantly higher than that of the control group at 176.88±62.67 seconds (P<0.001). Moreover, the duration of convulsion significantly decreased in which the lowest duration time (DT) of 7.00±4.68 seconds was observed when a high dosage of vitamin B12 at 85 µg/kg was injected two weeks prior to PTZ inoculation, which was significantly lower than that of the control group at 257.75±41.93 seconds (P<0.001). Lastly, the percentage of the population with PTZ-induced convulsion generally decreased after vitamin B12 pre-treatment in which majority showed more of simple less aggressive twitches rather than tonic-clonic seizures. Conclusion The results showed that vitamin B12 pre-treatment alleviates the seizure occurrence among PTZ-kindled rat models. These findings then suggest that vitamin B12 is a potential strategy and treatment for epilepsy and other related epileptogenesis activities.

Efficacy and Safety Profile of Ticagrelor Versus Clopidogrel in Percutaneous Coronary Intervention (PCI) for Acute Coronary Syndrome (ACS): A Systematic Review and Meta-Analysis.

The utilization of individualized anti-platelet therapy is of paramount significance in this era of cardiovascular advancement. This meta-analysis is also aiming to get more information relating to the effectiveness of ticagrelor versus clopidogrel among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). A comprehensive literature search was done through various databases like PubMed, Google Scholar, EMBASE, Web of Science, and the Cochrane Database Library from January 15, 2023, to February 23, 2023. After careful screening, eight articles with highly significant variables were involved in the synthesis of this meta-analysis. Data analysis was done through Review Manager (RevMan, Version 5.4; The Cochrane Collaboration, Copenhagen, Denmark). In our study, ticagrelor and clopidogrel were evaluated in 10614 and 14662 patients, respectively. Ticagrelor was significantly superior to Clopidogrel in terms of all-cause mortality (RR 0.79, 95% CI 0.69-0.91, p = 0.001), risk of MI (RR 0.74, 95% CI 0.61-0.89, p = 0.001), and stroke (RR 0.64, 95% CI 0.42-0.98, p = 0.04), but a higher risk of bleeding events was observed with Ticagrelor (RR 1.36, 95% CI 1.04-1.79, p = 0.03). The two regimens were comparable in terms of stent thrombosis. Ticagrelor was found to be best in terms of reducing post-PCI myocardial infarction, stroke, stent thrombosis, and all other mortality events in comparison to Clopidogrel. However, the bleeding events were of significant concern for the utilization of ticagrelor and required further investigations.

Revascularization Modalities in Acute Coronary Syndrome: A Review of the Current State of Evidence.

Acute coronary syndrome (ACS) stands as a leading global cause of mortality, underscoring the importance of effective prevention, early diagnosis, and timely intervention. While medications offer benefits to many patients, revascularization procedures such as coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and emerging hybrid approaches remain pivotal for ACS management. This review delves into the 2018 ESC/EACTS guidelines alongside an analysis of existing literature to shed light on the spectrum of revascularization methods. While both CABG and PCI demonstrate promising outcomes, the optimal choice between the two hinges on a comprehensive assessment of individual patient factors, anatomical complexity guided by advanced imaging, comorbidities, and age. The determination of whether to pursue culprit or total revascularization, as well as immediate or staged revascularization, is contingent upon various factors, including age, disease complexity, and clinical outcomes. This evidence-based decision-making process is orchestrated by a multidisciplinary heart team grounded in ongoing clinical evaluation. The primary objective of this review is to provide valuable insights into revascularization strategies and scrutinize the congruence of current guidelines with recent advancements in the field.

Medical students and risk of COVID-19 infection: A descriptive cross-sectional study from the University of Jordan.

BACKGROUNDS: The coronavirus disease-2019 (COVID-19) pandemic with increasing morbidity and mortality has impacted the lives of the global population, including medical education. With the return of on-site medical education in Jordan, it is important to know whether this would pose any risk of COVID-19 infection in medical students. OBJECTIVE: To investigate COVID-19 infection infection rates among medical students and whether there is difference between preclinical and clinical students' infection rate. METHODS: The study is a cross-sectional study, designed to (1) determine the incidence of COVID-19 in clinical and preclinical medical students (2) determine if there is a difference in infection rates between clinical and preclinical students. The study was situated at the University of Jordan and its affiliated hospitals. Data were collected from the 4th of December 2020 till the 17th of February 2021through a structured web-based questionnaire. RESULTS: A total of 1,830 responses were retrieved. Thirty-nine percent were males, and (61.5%) were females. Overall, 237(13%) of students reported testing positive for COVID-19 infection by PCR, of which 123 were clinical students (15.2%) and 114 were pre-clinical students (11.2%), representing a relative risk of 1.36 of COVID-19 infection among clinical students compared to pre-clinical students. This difference is statistically significant (P = 0.010). Rates of COVID-19 in females 13%; CI 7.5,18.4), were very close to those of males (12.9%; 95% CI 6.0,19.8). Positive COVID-19 cases peaked in November and October forming 36.3% and 32.9% of the cases, respectively. CONCLUSION: The incidence of positive COVID-19 tests was found to be higher among clinical students as compared to pre-clinical students. Commitment to general health safety precautions did not appear to be protective enough for clinical students. It is fundamental that additional strategies, including access to vaccines, are set, and deficiencies in current protections are identified to maintain students' safety and well-being.

Long-lasting modulation of synaptic plasticity in rat hippocampus after early-life complex febrile seizures.

A small fraction of children with febrile seizures appears to develop cognitive impairments. Recent studies in a rat model of hyperthermia-induced febrile seizures indicate that prolonged febrile seizures early in life have long-lasting effects on the hippocampus and induce cognitive deficits. However, data on network plasticity and the nature of cognitive deficits are conflicting. We examined three specific measures of hippocampal plasticity in adult rats with a prior history of experimental febrile seizures: (i) activity-dependent synaptic plasticity (long-term potentiation and depression) by electrophysiological recordings of Schaffer collateral/commissural-evoked field excitatory synaptic potentials in CA1 of acute hippocampal slices; (ii) Morris water maze spatial learning and memory; and (iii) hippocampal mossy fiber plasticity by Timm histochemistry and quantification of terminal sprouting in CA3 and the dentate gyrus. We found enhanced hippocampal CA1 long-term potentiation and reduced long-term depression but normal spatial learning and memory in adult rats that were subjected to experimental febrile seizures on postnatal day 10. Furthermore, rats with experimental febrile seizures showed modest but significant sprouting of mossy fiber collaterals into the inner molecular layer of the dentate gyrus in adulthood. We conclude that enhanced CA1 long-term potentiation and mild mossy fiber sprouting occur after experimental febrile seizures, without affecting spatial learning and memory in the Morris water maze. These long-term functional and structural alterations in hippocampal plasticity are likely to play a role in the enhanced seizure susceptibility in this model of prolonged human febrile seizures but do not correlate with overt cognitive deficits.

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

The Effect of Low-Doses of Caffeine and Taurine on Convulsive Seizure Parameters in Rats.

INTRODUCTION: Caffeine, an adenosine-receptor blocker, is believed to have neuronal excitatory effects, while Taurine, a mammalian amino acid, was shown to have neuroinhibitory effects. Aim: The aim of this study was to investigate the effects of acute and chronic administration of low doses of Caffeine and Taurine on the seizure threshold in rats. Methods: Six-week-old Sprague-Dawley male rats (n = 280) were divided randomly into five groups (control, acute caffeine intake, acute taurine intake, chronic caffeine intake and chronic taurine intake), with five subgroups per group according to five different doses of Pentylenetetrazole (PTZ) injections. Each subgroup consisted of eight rats. Data was entered and analyzed using Microsoft EXCEL and AddinsoftTM XLSTAT (Version 2012.6.06; New York, NY, USA). p-value = 0.05 was regarded as statistically significant. Results: There was a significant decrease in the latency of PTZ-induced seizures with both acute (p-value < 0.05) and chronic (p-value < 0.01) Caffeine treatment groups. Chronic exposure to Caffeine exhibited an increase in the probability of seizures (p-value < 0.05). However, acute exposure to Caffeine did not show a significant impact on the probability of seizures. Neither acute nor chronic exposures to Taurine had an effect on the probability of seizures, nor on the latency of PTZ-induced seizures. Discussion: Our study found that acute as well as chronic exposure to low doses of Caffeine (50 and 80 mg/kg) reduces the threshold, and hence increases the likelihood for seizures since it favors a state of neuronal hyper excitability through blocking of all adenosine receptors. On the other hand, acute or chronic exposure to Taurine did not show a significant effect on the PTZ-induced seizures parameters.

Effects of Memantine in a Mouse Model of Postoperative Cognitive Dysfunction.

Persistent impairment in cognitive functioning postoperatively is reported by clinical and animal studies, and is labeled as postoperative cognitive dysfunction (POCD). Evidence points to an exaggerated neuroinflammatory response resulting from peripheral systemic inflammation after surgery, with subsequent cytokine-induced glutamatergic excitotoxicity and synaptic impairment. These immunological changes, among many others, are also observed in Alzheimer's disease. Memantine is an N-methyl-D-aspartate receptor (NMDAR) antagonist commonly used to treat Alzheimer's disease. Surprisingly, little research exists on the role of memantine in preventing POCD. The purpose of this study is to investigate the effects of memantine on a spectrum of cognitive functions postoperatively. Mice were divided into 3 groups and each received treatment for 4 weeks. Placebo groups received a placebo then underwent either a sham procedure or a laparotomy procedure. The memantine group received memantine hydrochloride then underwent a laparotomy procedure. Cognitive tests were performed on postoperative days (POD) 1 and 7. Compared to sham-operated mice, placebo groups that underwent a laparotomy procedure showed impaired memory in the Morris water maze test, higher anxiety-like behavior in the open field and the elevated plus maze tests, increased depression-like behavior in the tail suspension test, and lack of preference for social novelty in the three-chamber test. On the other hand, memantine-treated mice that underwent a laparotomy procedure showed enhanced memory on POD7, improved depression-like behavior on POD1 and POD7, enhanced preference for social novelty on POD1, and no improvement in anxiety-like behavior. These findings suggest a potential protective effect of memantine in mice postoperatively on memory, depression-like behavior, and preference for social novelty.

Effect of chronic administration and withdrawal of caffeine on motor function, cognitive functions, anxiety, and the social behavior of BLC57 mice.

OBJECTIVES: The cognitive functions, motor coordination, and social behavior were studied in rodents after adding different doses of caffeine in their drinking water. METHODOLOGY: BLC57 mice were divided into four groups: Control (n = 8), chronic moderate dose (n = 8, Ch] MD), Ch high dose (n = 8, Ch HD), and withdrawal (n = 8, WD). Caffeine was administered for 1 month to all groups. Spatial memory was tested by Morris water maze, motor coordination by rotarod (RR), social behavior by (Crawley's test), and anxiety by elevated plus maze (EPM) test. RESULTS: In water maze, the latency to reach the platform was significantly shorter in Ch MD group compared to the control and the Ch HD groups. WD group showed the worst performance. RR results showed that the groups treated with caffeine performed poor in comparison to the control group where their latency to fall was significantly less. In the three-chamber test, the Ch MD group showed enhanced sociability (session 1) and social novelty behavior (session 2). On the other hand, both Ch HD and WD showed a lack in sociability and a deficit in social novelty. In the EPM, results showed that all caffeine administrated mice where more anxious than the control group. CONCLUSION: We concluded that chronic administration of caffeine in MD resulted in enhancement of spatial memory, motor functions, sociability, and social novelty. The anxiety in these animals was, however, increased. On the other hand, Ch HD caffeine had opposite effects on all the parameters except for anxiety.

Effects of enhanced environment and induced depression on cuprizone mouse model of demyelination.

Impairment in cognition and motor activity are commonly encountered in patients affected by multiple sclerosis (MS), and depression is believed to be a contributing factor. The aim of the present study was to investigate the impact of induced depression on a cuprizone mouse model of demyelination and the effectiveness of enhanced environment (EE) as a method of intervention. C57BL/6 male mice were divided into five groups: Cuprizone only (Cup-O), cuprizone undergoing depression (Cup-Dep), cuprizone housed in EE (Cup-EE), cuprizone housed in EE and undergoing depression (Cup-ED) and the control (n=9-10 per group). Depression was induced by repeated open-space forced swim. Neurobehavioral tests were conducted following a 6-week period of 0.2% cuprizone-enriched diet. The Cup-EE group performed significantly better in terms of cognition and motor functions, when compared with the Cup-O group, as evidenced by the Morris water maze (MWM; P<0.001) and rotarod performance test (P<0.05) results. Conversely, the Cup-Dep group exhibited a significant decline in performance in the MWM (P<0.001) and rotarod performance test (P<0.05), when compared with the Cup-O group. The Cup-ED group had comparable results to those of the Cup-O group, indicating a reversal of the induced depression effects. Open field test results failed to show an anxiety-like behavior in the cuprizone mouse model. It was therefore concluded that EE can improve MS-associated cognitive and motor deficits. Insights gained from these results facilitate the exploration of non-medical modes of intervention as an emerging adjuvant therapy in MS.

The Effect of Silver Nanoparticles on Learning, Memory and Social Interaction in BALB/C Mice.

Silver Nanoparticles (AgNPs), an epitome of nanotechnology, appear in everyday products such as water filters, printer ink, toothpaste, food packaging and cosmetics mostly due to their bactericidal properties. Given this high level of public exposure, the safety of AgNPs has never been fully established. The unsafe use of AgNPs could pose a real threat, not only to public health but also to economic growth in many industries. In this paper, we tested the effect of AgNPs on memory, learning, social behaviour and motor function of BALB/C mice. Outcomes of the present study suggested an impairment of these functions in AgNPs treated groups. Overall, obtained data support the evidence that the systemic exposure to AgNPs may result in alteration of the cerebral cognition and warrants further consideration on the impact of the AgNPs on human health with respect to their potential neurotoxicity.

Retrieval-Induced Forgetting in a Pentylenetetrazole-Induced Epilepsy Model in the Rat.

The selective retrieval of some information may lead to the forgetting of related, but non-retrieved information. This memory phenomenon is termed retrieval-induced forgetting (RIF). Active inhibition is thought to function to resolve interference from competing information during retrieval, which results in forgetting. Epilepsy is associated with impaired inhibitory control that contributes to executive dysfunction. The purpose of this study is to investigate whether rats in a kindling model of epilepsy demonstrate normal levels of RIF. Rats were divided into two groups: saline and kindling. Pentylenetetrazole was injected intraperitoneally until the rats kindled. RIF was tested using a modified version of the spontaneous object recognition test, consisting of a sample phase, retrieval or interference phase, and a test phase. Exploration time for each object was analyzed. RIF was demonstrated in the saline group when rats subjected to the retrieval phase failed to discriminate between the familiar object and the novel object later in the test phase. Kindled rats, on the other hand, did not suffer forgetting even when they were subjected to the retrieval phase, as they spent significantly longer times exploring the novel rather than the familiar object in the test phase. Therefore, RIF was not observed in the kindling group. These findings indicate impaired retrieval-induced forgetting in kindled rats, which may be suggestive of a deficit in the inhibitory control of memory.

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type 2 diabetes patients.

The mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function and altered mtDNA-CN reflects the oxidant-induced cell damage. A previous study by our group demonstrated that a reduction in the renal mtDNA-CN is implicated in the pathogenesis of diabetic nephropathy (DN), a leading cause of end-stage renal disease in diabetic patients. In the present study, it was investigated whether the mtDNA-CN in the peripheral blood may be utilized as a biomarker for DN in type 2 diabetes (T2D) patients. The study included 50 non-diabetic and 100 diabetic subjects. The diabetic subjects were sub-divided based on their albumin-to-creatinine ratio (ACR) into T2D patients with normoalbuminuria (n=50), DN patients with microalbuminuria (n=29) and DN patients with macroalbuminuria (n=21). The mtDNA-CN was measured in the peripheral blood by real-time polymerase chain reaction analysis. Patients with DN had a lower mtDNA-CN than patients with T2D and healthy controls (P<0.05). A sub-group analysis with stratification by the ACR indicated that a decreased mtDNA-CN was associated with the severity and the presence of DN, as it was lower in DN patients with macroalbuminuria than in DN patients with microalbuminuria and T2D patients with normoalbuminuria (P<0.01). The area under the receiver operating characteristic curve (AUC) for mtDNA-CN was 0.916 (sensitivity, 86% and specificity, 74%) and 0.961 (sensitivity, 96% and specificity, 88%) for differentiating DN patients from T2D patients without DN and from healthy controls, respectively. Furthermore, the AUC of mtDNA-CN for differentiating DN patients with microalbuminuria from those with macroalbuminuria was 0.895 (sensitivity, 83% and specificity, 85%). Multivariate analysis revealed that the mtDNA-CN was significantly associated with the occurrence and progression of DN, even after adjustment for age, mean blood pressure, glycated haemoglobin A1c and total cholesterol (P<0.05). In patients with DN, a decreased mtDNA-CN was negatively correlated with albuminuria and conventional risk factors for DN, and was positively correlated with the estimated glomerular filtration rate. The present results therefore suggest the utilization of circulating mtDNA-CN as a novel biomarker for the early diagnosis of DN and indicate the significance of decreased mtDNA-CN as another independent risk factor for DN.

Erythropoietin Protects Against Cognitive Impairment and Hippocampal Neurodegeneration in Diabetic Mice.

Administration of erythropoietin (EPO) is neuroprotective against a variety of experimentally-induced neurological disorders. The aim was to determine if EPO protects against hippocampal neurodegeneration as well as impairment of cognition and motor performance, associated with long-term diabetes. BALB/c mice were randomly allocated between control, diabetic and EPO-treated diabetic groups. EPO-treated diabetic mice were administered EPO 0.05 U/kg/day i.p. three times/week for 10 weeks. Cognition was assessed by Morris water maze. Brain samples were processed for light microscopic evaluation of hippocampus. Controls showed gradual improvement of cognitive performance in water maze when comparing latency (p < 0.01) and distance swum to reach the platform (p = 0.001). There was a similar trend for improvement in EPO-treated diabetics (p < 0.001). Latency did not improve in diabetic animals indicating lack of learning (p = 0.79). In probe trials, controls and EPO-treated diabetics spent more time in the training quadrant than expected by chance (p < 0.001). Diabetics did not show memory recall behavior; performance was significantly worse than expected by chance (p = 0.023). In diabetics, there was neurodegeneration in hippocampus and reduction in number of granule cells (p < 0.01) in the dentate gyrus. EPO treatment improved these neurodegenerative changes and preserved numbers of granule cells (p < 0.1, compared to controls). Erythropoietin treatment is protective against cognitive deficits and hippocampal neurodegeneration in diabetic mice.

Acute Administration of Caffeine: The Effect on Motor Coordination, Higher Brain Cognitive Functions, and the Social Behavior of BLC57 Mice.

Excessive caffeine consumption causes adverse health effects. The effects of moderate and high doses of caffeine consumption on the motor coordination, cognitive brain functions, and the social behavior in mice were studied. Animals were divided into three groups: control group, moderate dose group (Ac MD), and high dose group (Ac HD). The animals were tested after 7 days of caffeine administration. A rotarod test for motor coordination showed that the mice of the moderate dose group could stay on the rotating rod longer before falling in comparison to the control group and the high dose group. A water maze test for learning and memory showed better performance of mice receiving the moderate dose of caffeine compared to the other groups. Animals that were administered moderate as well as high doses of caffeine showed no sociability and no preference for social novelty in the three-chamber test used to test social behavior. In an elevated plus maze test, control animals showed no anxiety-like behavior while mice from both of the groups administered with caffeine showed anxiety-like behaviors. Our data conclude that the effects of caffeine on higher brain functions depend on the administration dose. When caffeine was given in moderate doses, it resulted in enhancement of memory and motor coordination functions. However, high doses caused defects in memory and learning. The social behavior of the mice, as determined by the level of anxiety and sociability, was affected negatively by moderate as well as high dose caffeine administration.

Streptozotocin-induced diabetes mellitus affects the NMDA receptors: Role of caffeine administration in enhancing learning, memory and locomotor deficits.

OBJECTIVE: To investigate the deterioration of the brain functions by diabetes mellitus (DM) and the beneficial effect of caffeine. MATERIALS AND METHODS: First, the component of N-methyl-D-aspartate receptors (NMDA) of the field excitatory postsynaptic potential (fEPSP) were recorded in streptozotocin (STZ)-induced DM and compared with control animals. Later, 40 mice were divided randomly into five groups (8 mice in each): (1) Normal control (Cont), (2) diabetic group (DM), (3) animals pretreated with i.p. caffeine before the induction of DM (Pre Caf), (4) acute caffeine-treated group (Ac Caf), and (5) chronic caffeine group (Ch Caf). Learning and memory were assessed in Morris-Water maze, and motor coordination was tested by rotarod. RESULTS: A significant reduction in the NMDA-component of the fEPSPs responses was recorded in the hippocampus of the diabetic animals. All the DM-groups demonstrated defects in learning and memory tasks; only the Ac Caf group could reverse the deteriorating effect of DM. This group showed a significantly lower latency values to reach their target (submerged platform) in the water maze in comparison to the DM, Pre Caf, and Ch Caf groups. Their performance was not significantly different from the control animals. Rotarod testing showed significant role of acute, but not chronic, caffeine administration in enhancing the motor skills. CONCLUSION: STZ -induced DM resulted into defects in memory tasks which are associated with a reduction in the hippocampal NMDA-receptor component of the fEPSP. Acute, but not chronic administration of caffeine could reverse the deteriorating effect of DM on learning and memory.