scholarly journals Effect of Metformin on Doxorubicin-Induced Memory Dysfunction

2020 ◽  
Vol 10 (3) ◽  
pp. 152
Author(s):  
Ibrahim Alharbi ◽  
Hindi Alharbi ◽  
Yasser Almogbel ◽  
Abdullah Alalwan ◽  
Ahmad Alhowail
Keyword(s):  
Cognitive Dysfunction ◽  
Memory Impairment ◽  
Elevated Plus Maze ◽  
Male Rats ◽  
Memory Impairments ◽  
Glucose Levels ◽  
Y Maze ◽  
Altered Glucose ◽  
Plus Maze ◽  
With Memory

Doxorubicin (DOX) is widely used to treat many types of cancer; however, it is associated with chemotherapy-related complications such as cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are currently no available therapeutic options. This study aims to examine whether metformin (MET) can protect against the neurotoxicity caused by DOX treatment. Forty male rats were divided into four groups (10 rats/group): control, DOX, DOX + MET, and MET. Rats treated with DOX received five doses of 4 mg/kg DOX weekly (cumulative dose: 20 mg/kg). For the DOX-MET and MET groups, MET (3 mg/mL) was dissolved in drinking water. Behavioral and glucose tests were performed one day after treatment was completed. We found DOX (4 mg/kg/week, 5 weeks) caused learning and memory impairment in the Y-maze, novel object recognition, and elevated plus maze behavioral tests. MET did not rescue these DOX-induced memory impairments. Neither DOX nor MET nor MET + DOX altered glucose levels following the treatment. In summary, DOX treatment is associated with memory impairment in rats, but MET does not rescue this cognitive dysfunction.

scholarly journals Calbindin-1 Expression in the Hippocampus following Neonatal Hypoxia-Ischemia and Therapeutic Hypothermia and Deficits in Spatial Memory

2018 ◽  
Vol 40 (5-6) ◽  
pp. 508-522 ◽  
Author(s):  
Janasha Goffigan-Holmes ◽  
Dafne Sanabria ◽  
Johana Diaz ◽  
Debra Flock ◽  
Raul Chavez-Valdez
Keyword(s):  
Therapeutic Hypothermia ◽  
Neurodegenerative Disorders ◽  
Memory Impairment ◽  
Memory Deficits ◽  
Nissl Staining ◽  
Memory Impairments ◽  
Neonatal Hypoxia ◽  
Y Maze ◽  
Hypoxia Ischemia ◽  
With Memory

Hippocampal injury following neonatal hypoxia-ischemia (HI) leads to memory impairments despite therapeutic hypothermia (TH). In the hippocampus, the expression of calbindin-1 (Calb1), a Ca2+-buffering protein, increases during postnatal development and decreases with aging and neurodegenerative disorders. Since persistent Ca2+ dysregulation after HI may lead to ongoing injury, persistent changes in hippocampal expression of Calb1 may contribute to memory impairments after neonatal HI. We hypothesized that, despite TH, neonatal HI persistently decreases Calb1 expression in the hippocampus, a change associated with memory deficits in the mouse. We induced cerebral HI in C57BL6 mice at postnatal day 10 (P10) with right carotid ligation and 45 min of hypoxia (FiO2 = 0.08), followed by normothermia (36°C, NT) or TH (31°C) for 4 h with anesthesia-shams as controls. Nissl staining and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) were used to grade brain injury and astrogliosis at P11, P18, and P40 prior to the assessment of Calb1 expression by IHC. The subset of mice followed to P40 also performed a memory behavior task (Y-maze) at P22–P26. Nonparametric statistics stratified by sex were applied. In both anterior and posterior coronal brain sections, hippocampal Calb1 expression doubled between P11 and P40 due to an increase in the cornus ammonis (CA) field (Kruskal-Wallis [KW] p < 0.001) and not the dentate gyrus (DG). Neonatal HI produced delayed (P18) and late (P40) deficits in the expression of Calb1 exclusively in the CA field (KW p = 0.02) in posterior brain sections. TH did not attenuate Calb1 deficits after HI. Thirty days after HI injury (at P40), GFAP scores in the hippocampus (p < 0.001, r = –0.47) and CA field (p < 0.001, r = –0.39) of posterior brain sections inversely correlated with their respective Calb1 expression. Both sexes demonstrated deficits in Y-maze testing, including approximately 40% lower spontaneous alterations performance and twice as much total impairment compared to sham mice (KW p < 0.001), but it was only in females that these deficits correlated with the Calb1 expression in the hippocampal CA field (p < 0.05) of the posterior sections. Hippocampal atrophy after neonatal HI also correlated with worse deficits in Y-maze testing, but it did not predict Calb1 deficits. Neonatal HI produces a long-lasting Calb1 deficit in the hippocampal CA field during development, which is not mitigated by TH. Late Calb1 deficit after HI may be the result of persistent astrogliosis and can lead to memory impairment, particularly in female mice.

scholarly journals Modification of NO-cGMP Pathway Differentially Affects Diazepam- and Flunitrazepam-Induced Spatial and Recognition Memory Impairments in Rodents

2019 ◽  
Vol 37 (4) ◽  
pp. 1036-1046 ◽  
Author(s):  
Jolanta Orzelska-Górka ◽  
Piotr Bernat ◽  
Piotr Tutka ◽  
Joanna Listos ◽  
Ewa Kędzierska ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Recognition Memory ◽  
Animal Behavior ◽  
Memory Impairment ◽  
Elevated Plus Maze ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Memory Impairments ◽  
Plus Maze ◽  
Cgmp Pathway

AbstractThis study investigated the influence of sildenafil and methylene blue (MB), two modulators of the nitric oxide (NO)-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway on amnesic effects of two benzodiazepines (BZs) (diazepam (DZ) and flunitrazepam (FNZ)), in rodents—mice and rats. In the modified elevated plus maze (mEPM) and novel object recognition (NOR) tests, MB given ip at a dose of 5 mg/kg 5 min prior to DZ administration (0.25 or 1 mg/kg, sc) enhanced/induced memory impairment caused by DZ. When MB (2.5, 5, and 10 mg/kg) was applied 5 min prior to FNZ administration (0.05 and 0.1 mg/kg), an effect was opposite and memory impairment induced by FNZ was reduced. When sildenafil (2.5 and 5 mg/kg, ip) was applied 5 min prior to DZ, we observed a reduction of DZ-induced memory deficiency in the mEPM test. A similar effect of sildenafil was shown in the NOR test when the drug was applied at doses of 1.25, 2.5, and 5 mg/kg prior to DZ. In the mEPM test, sildenafil at abovementioned doses had no effects on FNZ-induced memory impairment. In turns, sildenafil administered at doses of 2.5 and 5 mg/kg increased the effect of FNZ on memory impairment in the NOR test. In conclusion, the NO-cGMP pathway is involved differentially into BZs-induced spatial and recognition memory impairments assessed using the NOR and mEPM tests. Modulators of the NO-cGMP pathway affect animal behavior in these tests in a different way depending on what benzodiazepine is applied.

scholarly journals Aqueous Extract of Semen Ziziphi Spinosae Exerts Anxiolytic Effects during Nicotine Withdrawal via Improvement of Amygdaloid CRF/CRF1R Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Changhong Gu ◽  
ZhengLin Zhao ◽  
Xiaodong Zhu ◽  
Tong Wu ◽  
Bong Hyo Lee ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Elevated Plus Maze ◽  
Plasma Corticosterone ◽  
Nicotine Withdrawal ◽  
Corticotropin Releasing Factor ◽  
Central Nucleus ◽  
Male Rats ◽  
General Anxiety ◽  
Plus Maze

Anxiety during nicotine withdrawal (NicW) is a key risk factor for smoking relapse. Semen Ziziphi Spinosae (SZS), which is a prototypical hypnotic-sedative herb in Oriental medicine, has been clinically used to treat insomnia and general anxiety disorders for thousands of years. Thus, the present study evaluated the effects of the aqueous extract of SZS (AESZS) on NicW-induced anxiety in male rats that received subcutaneous administrations of nicotine (Nic) (0.4 mg/kg, twice a day) for 7 d followed by 4 d of withdrawal. During NicW, the rats received four intragastric treatments of AESZS (60 mg/kg/d or 180 mg/kg/d). AESZS dose-dependently attenuated NicW-induced anxiety-like behaviors in the elevated plus maze (EPM) tests and 180 mg/kg/d AESZS inhibited NicW-induced increases in plasma corticosterone. Additionally, the protein and mRNA expressions of corticotropin-releasing factor (CRF) and CRF type 1 receptor (CRF1R) increased in the central nucleus of the amygdala (CeA) during NicW, but these changes were suppressed by 180 mg/kg/d AESZS. A post-AESZS infusion of CRF into the CeA abolished the attenuation of anxiety by AESZS and 180 mg/kg/d AESZS suppressed NicW-induced increases in norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the CeA. The present results suggest that AESZS ameliorated NicW-induced anxiety via improvements in CRF/CRF1R and noradrenergic signaling in the CeA.

scholarly journals Ebselen Prevents Cigarette Smoke-Induced Cognitive Dysfunction In Mice By Preserving Hippocampal Synaptophysin Expression

2021 ◽  
Author(s):  
Simone N. De Luca ◽  
Kurt Brassington ◽  
Stanley M. H. Chan ◽  
Aleksandar Dobric ◽  
Kevin Mou ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Dysfunction ◽  
Memory Impairment ◽  
Microglial Activation ◽  
Pulmonary Inflammation ◽  
Systemic Circulation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Memory Impairments ◽  
The Brain

Abstract Background: Cigarette smoking (CS) is the leading cause of chronic obstructive pulmonary disease (COPD). The “spill-over” of pulmonary inflammation into the systemic circulation may damage the brain, leading to cognitive dysfunction. Cessation of CS can improve pulmonary and neurocognitive outcomes, however, its benefit on the neuroinflammatory profile remains uncertain. Here, we investigate how CS exposure impairs neurocognition and whether this can be reversed with CS cessation or an antioxidant treatment. Methods: Male BALB/c mice were exposed CS (9 cigarettes/day for 8 weeks) followed by 4 weeks of CS cessation. Another cohort of CS-exposed mice were co-administrated with a glutathione peroxidase (Gpx) mimetic, ebselen (10mg/kg) or vehicle (5% CM-cellulose). We assessed pulmonary inflammation, spatial and working memory, and the hippocampal microglial, oxidative and synaptic profiles. Results: CS exposure increased lung inflammation which was reduced following CS cessation. CS caused spatial and working memory impairments which were attributed to hippocampal microglial activation and suppression of synaptophysin. CS cessation did not improve memory deficits or alter microglial activation. Ebselen completely prevented the CS-induced working and spatial memory impairments, which was associated with restored synaptophysin expression without altering microglial activation.Conclusion: We were able to model the CS-induced memory impairment and microglial activation seen in human COPD. The preventative effects of ebselen on memory impairment is likely to be dependent on a preserved synaptogenic profile. Cessation alone also appears to be insufficient in correcting the memory impairment, suggesting the importance of incorporating antioxidant therapy to help maximizing the benefit of cessation.

scholarly journals High-Fat Diet Enhances Working Memory in the Y-Maze Test in Male C57BL/6J Mice with Less Anxiety in the Elevated Plus Maze Test

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2036 ◽  
Author(s):  
Kaichi Yoshizaki ◽  
Masato Asai ◽  
Taichi Hara
Keyword(s):  
Working Memory ◽  
Body Weight ◽  
High Fat Diet ◽  
Elevated Plus Maze ◽  
High Fat ◽  
Behavioral Traits ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Y Maze ◽  
Plus Maze

Obesity is characterized by massive adipose tissue accumulation and is associated with psychiatric disorders and cognitive impairment in human and animal models. However, it is unclear whether high-fat diet (HFD)-induced obesity presents a risk of psychiatric disorders and cognitive impairment. To examine this question, we conducted systematic behavioral analyses in C57BL/6J mice (male, 8-week-old) fed an HFD for 7 weeks. C57BL/6J mice fed an HFD showed significantly increased body weight, hyperlocomotion in the open-field test (OFT) and Y-maze test (YMZT), and impaired sucrose preference in the sucrose consumption test, compared to mice fed a normal diet. Neither body weight nor body weight gain was associated with any of the behavioral traits we examined. Working memory, as assessed by the YMZT, and anxiety-like behavior, as assessed by the elevated plus maze test (EPMT), were significantly correlated with mice fed an HFD, although these behavioral traits did not affect the entire group. These results suggest that HFD-induced obesity does not induce neuropsychiatric symptoms in C57BL/6J mice. Rather, HFD improved working memory in C57BL/6J mice with less anxiety, indicating that an HFD might be beneficial under limited conditions. Correlation analysis of individual traits is a useful tool to determine those conditions.

Effect of Surfagon on Open Field and Elevated Plus Maze Behavior of Gonadectomized and Non-Gonadectomized Male Rats

2019 ◽  
Vol 168 (1) ◽  
pp. 52-54
Author(s):  
O. O. Masalova ◽  
S. B. Kazakova ◽  
T. N. Savateeva-Lyubimova ◽  
K. V. Sivak ◽  
N. S. Sapronov ◽  
...  
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Male Rats ◽  
Plus Maze

scholarly journals SHODHANA DECREASES NOOTROPIC ACTIVITY OF SEMECARPUS ANACARDIUM

2016 ◽  
pp. 294
Author(s):  
Pratap Kumar Sahu ◽  
Mishra Sk ◽  
Rout K ◽  
Prusty Sk
Keyword(s):  
Radial Maze ◽  
Elevated Plus Maze ◽  
Methanolic Extract ◽  
Nootropic Activity ◽  
Alternation Behavior ◽  
Spontaneous Alternation Behavior ◽  
Semecarpus Anacardium ◽  
Y Maze ◽  
Plus Maze

<p>ABSTRACT<br />Objective: To evaluate the nootropic activity of methanolic extract of pre-shodhit and shodhit Semecarpus anacardium (SA) nuts and to observe the<br />effect of shodhana on nootropic activity of SA.<br />Methods: Spatial learning and working memory was considered for evaluation. The parameters used were spontaneous alternation behavior<br />(Y-maze), number of correct responses (radial maze), and transfer latency in day 1 (elevated plus maze). Scopolamine, an anticholinergic drug, was<br />used to induce cognitive deficit. % inhibition of acetylcholine esterase (AChE) was measured in vitro.<br />Results: Both pre-shodhit and shodhit drug reversed the scopolamine-induced a decrease in percentage spontaneous alternation behavior in Y-maze<br />and number of correct responses in radial maze. Scopolamine-induced increase in transfer latency in elevated plus maze was significantly decreased<br />by pre-shodhit drug only. Shodhit drug has no significant effect on transfer latency. Both pre-shodhit and shodhit drug showed dose-dependent<br />inhibition of AChE activity in vitro. Pre-shodhit drug showed a more nootropic activity than shodhit drug.<br />Conclusion: Methanolic extract of the nuts of S. anacardium possesses nootropic activity which may be attributed to inhibition of cholinesterase<br />activity. Shodhana of the nuts decreases nootropic activity.<br />Keywords: Semecarpus anacardium, Acetylcholine esterase, Shodhana, Nootropic.</p>

Effects of NOS inhibitors on the benzodiazepines-induced memory impairment of mice in the modified elevated plus-maze task

2013 ◽  
Vol 244 ◽  
pp. 100-106 ◽  
Author(s):  
Jolanta Orzelska ◽  
Sylwia Talarek ◽  
Joanna Listos ◽  
Sylwia Fidecka
Keyword(s):  
Memory Impairment ◽  
Elevated Plus Maze ◽  
Maze Task ◽  
Plus Maze ◽  
Nos Inhibitors

scholarly journals Effect of Short Time Exposure of Local ELF-MFs on Sleepiness Induced in Male Rats

2021 ◽  
Vol 0 (0) ◽  
pp. 1-22
Author(s):  
Elnaz Azizi ◽  
◽  
Fatemeh Ayoobi ◽  
Ali Shamsizadeh ◽  
Amir Moghadam-Ahmadi ◽  
...  
Keyword(s):  
Serum Level ◽  
Open Field ◽  
Field Test ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Male Rats ◽  
Time Exposure ◽  
Plus Maze ◽  
Before And After ◽  
Short Time

Introduction: Lack of high-quality sleep causes serious side effects like anxiety and changes in plasma concentration of oxalate. The current study aimed to investigate the impact of local extremely low frequency magnetic fields (ELF-MFs) on inducing sleep (sleepiness) and anxiety in male rats. Methods: In this experimental study, 40 male rats were allocated in four groups (n=10). The ELF-MFs exposure (0, 10 and 18 Hz) was applied with intensity 200µT for three days (10 min/day). Sham-treated animal did not receive ELF-MF. Serum level of oxalic acid (OA) and sleepiness were measured both before first and after last exposure to ELF-MF or sham. Anxiety, sleepiness and OA were measured by using elevated plus maze, open-field test (OFT) and ELISA test, respectively. Results: Comparison of oxalate levels between before and after exposure to ELF-MF revealed that ELF-MF (10 Hz) decreased the serum level of oxalate (p<0.05). Comparison of the percent of open:closed arm entry (in elevated plus maze) between before and after exposure to ELF-MF revealed significant differences. Also, frequency, velocity and distance moved were decreased in the open-field test. Conclusion: Results of the present study demonstrated that ELF-MF with short time exposure may modulate the metabolism of OA and may modulate anxiety-like behavior or kind of induction of sleepiness in male rats.

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