Effects Of Immediate Administration Research Articles

The role of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type receptor modulators in object recognition memory reconsolidation

Numerous studies suggest that the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type (AMPA) receptor appears to play a central role in mediating brain functions, such as learning and memory. Trafficking of this receptor is related to different long-term memory processes. This study explores the role of two AMPA receptor (AMPAR) modulators in object recognition memory (ORM) reconsolidation. First, the effects of immediate administration of each drug after memory reactivation were investigated and compared. Then, this drug's efficient time window and its effects without memory reactivation were investigated. Immediate CX546 administration after reactivation did not affect ORM reconsolidation. In contrast, administration of 10-mg/kg NBQX significantly impaired ORM reconsolidation within a 6-h time window. Importantly, the observed effects were not attributed to the exploratory behavior or locomotor activity of mice. These findings provide new evidence that the AMPA receptor plays an important role in the reconsolidation phase of ORM.

Low-dose metformin treatment in the subacute phase improves the locomotor function of a mouse model of spinal cord injury.

Metformin, a first-line drug for type-2 diabetes, has been shown to improve locomotor recovery after spinal cord injury. However, there are studies reporting no beneficial effect. Recently, we found that high dose of metformin (200 mg/kg, intraperitoneal) and acute phase administration (immediately after injury) led to increased mortality and limited locomotor function recovery. Consequently, we used a lower dose (100 mg/kg, i.p.) metformin in mice, and compared the effect of immediate administration after spinal cord injury (acute phase) with that of administration at 3 days post-injury (subacute phase). Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale (BMS) scoring. Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site. Furthermore, metformin treatment at the subacute phase reduced neutrophil infiltration. These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin. These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection. This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch (approval No. 1008041C) in 2010.

Testosterone Reduces Spinal Cord Injury-Induced Effects on Male Reproduction by Preventing CADM1 Defect.

Objective This study evaluated the effects of exogenous testosterone molecule-1 (CADM1) pathological defect during early and chronic periods of spinal cord injury (SCI). Materials and Methods In this experimental study, testosterone was administered immediately or after one week of SCI induction. Along with quantification of CADM1 gene expression and its immunoreactivity, we evaluated sperm parameters and serum testosterone level post-SCI. Results Different grades of abnormalities in sperm parameters and testis architecture were observed along with significant reductions in the level of CADM1 expression and its immunoreactivity in the seminiferous tubules of both acute and chronic SCI groups. Exogenous testosterone, by compensating the serum testosterone level. reduced the percentage of apoptotic and both short head and abnormal sperm froms in the caudal epididymis. Importantly, the beneficial effects of immediate administration of testosterone were prominent. Increases in the level of CADM1 transcription and its immunoreactivity in the testis of SCI mice treated with testosterone were accompanied by improvement of sperm motility as well as testicular Johnsen’s and Miller’s criteria. ConclusionSince immediate testosterone treatment improved the immunoreactivity and transcription level of CADM1, the observed beneficial effect of exogenouse testosterone can be attributed to its effect on CADM1 dynamics.

Gastrin-releasing peptide attenuates fear memory reconsolidation

BackgroundGastrin Releasing Peptide (GRP) may play a role in fear learning. The GRP Receptor is expressed in the basolateral amygdala and hippocampus, and central administration of GRP mediates fear learning. The effects of GRP on reconsolidation, however, have been minimally explored. Reconsolidation, the process by which formed memories are rendered labile following recall, provides a window of opportunity for pharmacological intervention. Although evidence suggests the window of opportunity to alter reactivated consolidation memory can be as long as 6 h, shorter intervals have not been extensively investigated. MethodMale Sprague-Dawley rats received six 1.0 mA continuous footshocks. 24 h later, were re-exposed to the context (shock chamber). Immediately following memory retrieval rats received i.p. injection of GRP (10 nmol/kg), Flumazenil (1 mg/kg), GRP + Flumazenil (10 nmol/kg GRP with 1 mg/kg Flumazenil), or Vehicle. Other groups received GRP or Vehicle at 0, 10, 30, or 60 min post-reactivation. 24 h and 5 days later rats were assessed for fear expression upon re-exposure to the fearful stimulus. ResultsGRP significantly attenuated the reconsolidation of learned fear when administered immediately (but not 10 min or longer) following recall. Some of the variability in the impact of treatments aimed at disrupting fear memories may be governed, in part, by the time-frame of the reconsolidation window. Our results indicate that the effect of immediate administration persisted for at least 5 days. Co-administration of benzodiazepine-receptor antagonist Flumazenil blocked this effect, suggesting the effect is mediated via a GABAergic mechanism.

ACTIVATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-β/δ ATTENUATES MYOCARDIAL ISCHEMIA/REPERFUSION INJURY IN THE RAT

Peroxisome proliferator-activated receptor-beta/delta (PPAR-beta/delta) is a transcription factor that belongs to the PPAR nuclear hormone receptor family. There is little information about the effects of the immediate administration of specific ligands of PPAR-beta/delta (e.g., GW0742) in animal models of myocardial I/R injury. Using a rat model of regional myocardial I/R in vivo, we have investigated the effects of immediate administration of GW0742 on myocardial infarct size. Male Wistar rats were subjected to 25 min of regional ischemia followed by 2 h of reperfusion and treated with GW0742 (3, 30, or 300microg/kg i.v. given at 30 min before ischemia and again at the start of reperfusion). Higher doses (30 or 300 microg/kg i.v.) of GW0742 caused a reduction in infarct size, whereas the lowest dose used was not effective. The degree of cardioprotection was similar when GW0742 (30 microg/kg i.v.) was given on reperfusion alone. The reduction in infarct size afforded by GW0742 was not reduced by the competitive irreversible PPAR-alpha antagonist GW6471 (1 mg/kg i.v., 15 min before ischemia). GW0742 (30 microg/kg i.v.) reduced the I/R-induced (a) decrease in the phosphorylation of Akt and glycogen synthase kinase-3beta, (b) nuclear translocation of the p65 subunit of nuclear factor-kappaB (activation of nuclear factor-kappaB), and (c) increase in the expression of iNOS and cyclooxygenase-2. Thus, immediate administration of the PPAR-beta/delta ligand GW0742 during reperfusion reduces myocardial infarct size in the rat by a mechanism that may involve inhibition of the activity of glycogen synthase kinase-3beta secondary to activation of the Akt pathway.

Effect of immediate neonatal zidovudine on prevention of vertical transmission of human immunodeficiency virus type 1

Objectives: To describe the effects of various short zidovudine (ZDV) prophylactic regimens on vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection, especially the effect of immediate neonatal ZDV prophylaxis. Materials and Methods: The study included children of HIV-1-infected mothers who were born at a teaching hospital in Bangkok. The ZDV prophylaxis regimens varied by time periods that included: (1) no ZDV (1991–1996); (2) antenatal oral ZDV, 250 mg given twice a day starting at 34 to 36 weeks' gestation and continued until labor (1995–1998); (3) antenatal oral ZDV plus immediate neonatal oral ZDV, 6 mg/0.6 mL/dose started within the first 2 hours after birth and continued at 6-hour intervals for 4 to 6 weeks (1997–1998); and (4) intrapartum intravenous ZDV given in addition to regimen 3 (1998–1999). Neonatal ZDV was administered within 2 hours after birth in 95% of the neonates. Results: In a cohort of 136 children born at least 9 months before the analysis date, the HIV-1 vertical infection rates were: (1) no ZDV, 11 of 48 (22.9%, 95% confidence interval [Cl] = 12.0–37.3); (2) late antenatal ZDV, 10 of 47 (21.3%, 95% Cl = 10.7–35.7); (3) late antenatal ZDV plus immediate neonatal ZDV, 0 of 28 (0%, 95% Cl = 0–12.3); (4) late antenatal, intrapartum intravenous ZDV, plus immediate neonatal ZDV, 0 of 13 (0%, 95% Cl = 0–24.7). An estimated 0% (95% Cl = 0–8.6) of the infants who received immediate neonatal ZDV with or without intrapartum ZDV were infected, as compared with 22.1% (95% Cl = 14.2–31.8 ) of those who received no ZDV or only late antenatal ZDV (P < 0.001). Conclusion: The results of this study suggests high protective effect of immediate administration of neonatal ZDV. Perinatal components of antiretroviral prophylaxis provided the best results for protecting against vertical HIV-1 transmission.