scholarly journals Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 650
Author(s):  
Malgorzata Lopatynska-Mazurek ◽  
Anna Antolak ◽  
Pawel Grochecki ◽  
Ewa Gibula-Tarlowska ◽  
Anna Bodzon-Kulakowska ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Spatial Memory ◽  
Spatial Learning ◽  
Reversal Learning ◽  
Neonatal Period ◽  
Ethanol Exposure ◽  
Control Group ◽  
Adult Rats ◽  
Altered Expression ◽  
The Impact

Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1.5 g/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 and 10 mg/kg) was given before intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4–9 (an equivalent to the third trimester of human pregnancy). Spatial memory/reversal learning and rewarding ethanol effect were evaluated in adult (PND60–70) rats. Additionally, the impact of rapamycin pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the brain was assessed in adult rats. Our results show that neonatal ethanol exposure induced deficits in spatial memory and reversal learning in adulthood, but the reversal learning outcome may have been due to spatial learning impairments rather than cognitive flexibility impairments. Furthermore, in adulthood the ethanol treated rats were also more sensitive to the rewarding effect of ethanol than the control group. Rapamycin prevented the neonatal effect of ethanol and normalized the GluN2B down-regulation in the hippocampus and the prefrontal cortex, as well as normalized this subunit’s up-regulation in the striatum of adult rats. Our results suggest that rapamycin and related drugs may hold promise as a preventive therapy for fetal alcohol spectrum disorders.

scholarly journals Effects of Mephedrone and Amphetamine Exposure during Adolescence on Spatial Memory in Adulthood: Behavioral and Neurochemical Analysis

2021 ◽  
Vol 22 (2) ◽  
pp. 589
Author(s):  
Pawel Grochecki ◽  
Irena Smaga ◽  
Malgorzata Lopatynska-Mazurek ◽  
Ewa Gibula-Tarlowska ◽  
Ewa Kedzierska ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Spatial Memory ◽  
Reversal Learning ◽  
Drug Effects ◽  
Long Term Effects ◽  
Delayed Effect ◽  
Adult Rats ◽  
Neurochemical Analysis ◽  
Learning Impairment

A synthetic cathinone, mephedrone is widely abused by adolescents and young adults. Despite its widespread use, little is known regarding its long-term effects on cognitive function. Therefore, we assessed, for the first time, whether (A) repeated mephedrone (30 mg/kg, i.p., 10 days, once a day) exposure during adolescence (PND 40) induces deleterious effects on spatial memory and reversal learning (Barnes maze task) in adult (PND 71–84) rats and whether (B) these effects were comparable to amphetamine (2.5 mg/kg, i.p.). Furthermore, the influence of these drugs on MMP-9, NMDA receptor subunits (GluN1, GluN2A/2B) and PSD-95 protein expression were assessed in adult rats. The drug effects were evaluated at doses that per se induce rewarding/reinforcing effects in rats. Our results showed deficits in spatial memory (delayed effect of amphetamine) and reversal learning in adult rats that received mephedrone/amphetamine in adolescence. However, the reversal learning impairment may actually have been due to spatial learning rather than cognitive flexibility impairments. Furthermore, mephedrone, but not amphetamine, enhanced with delayed onset, MMP-9 levels in the prefrontal cortex and the hippocampus. Mephedrone given during adolescence induced changes in MMP-9 level and up-regulation of the GluN2B-containing NMDA receptor (prefrontal cortex and hippocampus) in young adult (PND 63) and adult (PND 87) rats. Finally, in adult rats, PSD-95 expression was increased in the prefrontal cortex and decreased in the hippocampus. In contrast, in adult rats exposed to amphetamine in adolescence, GluN2A subunit and PSD-95 expression were decreased (down-regulated) in the hippocampus. Thus, in mephedrone—but not amphetamine-treated rats, the deleterious effects on spatial memory were associated with changes in MMP-9 level. Because the GluN2B-containing NMDA receptor dominates in adolescence, mephedrone seems to induce more harmful effects on cognition than amphetamine does during this period of life.

scholarly journals Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1βas a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lukasz Markiewicz ◽  
Dariusz Pytel ◽  
Bartosz Mucha ◽  
Katarzyna Szymanek ◽  
Jerzy Szaflik ◽  
...  
Keyword(s):  
Risk Factor ◽  
Aqueous Humor ◽  
Open Angle Glaucoma ◽  
Luciferase Assay ◽  
Control Group ◽  
Promoter Regions ◽  
Altered Expression ◽  
Expression Levels ◽  
The Impact

The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2GMMP1, -1562 C/TMMP9, -82 A/GMMP12, -511 C/TIL-1β, and 372 T/CTIMP1genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA.In vivopromoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression ofMMP1,MMP9,MMP12, andIL-1βgenes as compared to the control group (P<0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1βcompared to the control group (P<0.001). Allele -1607 1G ofMMP1gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C ofMMP9gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.

Western diet in the perinatal period promotes dysautonomia in the offspring of adult rats

2016 ◽  
Vol 8 (2) ◽  
pp. 216-225 ◽  
Author(s):  
R. Vidal-Santos ◽  
F. N. Macedo ◽  
M. N. S. Santana ◽  
V. U. De Melo ◽  
J. L. de Brito Alves ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Systolic Arterial Pressure ◽  
Perinatal Period ◽  
Western Diet ◽  
Control Group ◽  
Standard Diet ◽  
Adult Rats ◽  
Male Wistar Rats ◽  
The Impact

The present study investigated the impact of a western diet during gestation and lactation on the anthropometry, serum biochemical, blood pressure and cardiovascular autonomic control on the offspring. Male Wistar rats were divided into two groups according to their mother’s diet received: control group (C: 18% calories of lipids) and westernized group (W: 32% calories of lipids). After weaning both groups received standard diet. On the 60th day of life, blood samples were collected for the analysis of fasting glucose and lipidogram. Cardiovascular parameters were measured on the same period. Autonomic nervous system modulation was evaluated by spectrum analysis of heart rate (HR) and systolic arterial pressure (SAP). The W increased glycemia (123±2v. 155±2 mg/dl), low-density lipoprotein (15±1v. 31±2 mg/dl), triglycerides (49±1v. 85±2 mg/dl), total cholesterol (75±2v. 86±2 mg/dl), and decreased high-density lipoprotein (50±4v. 38±3 mg/dl), as well as increased body mass (209±4v. 229±6 g) than C. Furthermore, the W showed higher SAP (130±4v. 157±2 mmHg), HR (357±10v. 428±14 bpm), sympathetic modulation to vessels (2.3±0.56v. 6±0.84 mmHg2) and LF/HF ratio (0.15±0.01v. 0.7±0.2) than C. These findings suggest that a western diet during pregnancy and lactation leads to overweight associated with autonomic misbalance and hypertension in adulthood.

scholarly journals Effect of sub-chronic intermittent ethanol exposure on spatial learning and ethanol sensitivity in adolescent and adult rats

Alcohol ◽  
2014 ◽  
Vol 48 (4) ◽  
pp. 353-360 ◽  
Author(s):  
H.S. Swartzwelder ◽  
A. Hogan ◽  
M-Louise Risher ◽  
Rita A. Swartzwelder ◽  
Wilkie A. Wilson ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Ethanol Exposure ◽  
Ethanol Sensitivity ◽  
Adult Rats ◽  
Chronic Intermittent Ethanol ◽  
Chronic Intermittent Ethanol Exposure

scholarly journals Comparing the Impact of Long-Term Exposure to Extremely Low-Frequency Electromagnetic Fields With Diverse Values on Anxiety, Memory, Learning, And Β-Amyloid Deposition In Adult Rats

2021 ◽  
pp. 1-24
Author(s):  
Nafiseh Faraji ◽  
◽  
Iraj Salehi ◽  
Akram Alizadeh ◽  
Arash Pourgholaminejad ◽  
...  
Keyword(s):  
Electromagnetic Fields ◽  
Low Frequency ◽  
Amyloid Deposition ◽  
Control Group ◽  
Adult Rats ◽  
Male Adult ◽  
Extremely Low Frequency ◽  
Β Amyloid ◽  
The Impact ◽  
The Brain

Background: Extremely low-frequency electromagnetic fields (ELF-EMFs) have gathered significant consideration for their possible pathogenicity. However, their effects on nervous system functions were not fully clarified. In this study, our aim was to assay the effect of ELF-EMFs with different intensity on memory, anxiety, antioxidant activity, beta amyloid (Aβ) deposition and microglia population in rats. Materials and Methods: Fifty male adult rats were randomly separated into 5 groups; four groups exposed to a flux density of 1, 100, 500 and 2000 microtesla (µT), 50 Hertz (Hz) frequency for 1h/day for 2 months and one group as a control group. The control group were without ELF-EMF stimulation. After 8 weeks, passive avoidance and elevated plus maze (EPM) tests was performed to assess memory formation and anxiety-like behavior, respectively. Total free thiol groups and the index of lipid peroxidation were assessed. Also, for detection of β-Amyloid deposition and stained microglia in the brain, anti-β-amyloid and anti-Iba1 antibodies were used. Results: In the ELF-EMF exposure groups, the step-through latency was significantly greater in the retention test (100,500, and 2000 µT) than in the control group (P<0.05). Also, the percentage of the entries into the open arms in ELF-EMF exposure groups (especially 2000 µT) decreased than control group (P <0.05). No β-Amyloid depositions were detected in the hippocampus of different groups. An increase in microglia numbers in the 100, 500 and 2000 µT groups was observed in compare to the control and 1 µT group. Conclusion: Exposure to ELF-EMF had an anxiogenic effect on rats and promoted memory and also induced oxidative stress. No β-Amyloid depositions were detected in the brain. Also, positive effect of ELF-EMF was observed on population of microglia population in the brain.

scholarly journals Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 978
Author(s):  
Bei-Hao Shiu ◽  
Ming-Hong Hsieh ◽  
Wen-Chien Ting ◽  
Ming-Chih Chou ◽  
Lun-Ching Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Control Group ◽  
Global Public Health ◽  
Altered Expression ◽  
Public Health Burden ◽  
Individual Snps ◽  
Incidence And Mortality ◽  
The Impact

Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of FGFR4 gene polymorphisms on the risk and progression of CRC. Three FGFR4 single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; p = 0.046) or rs351855 (GA and AA; AOR, 0.191; p = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression.

scholarly journals Selective H3 Antagonist (ABT-239) Differentially Modifies Cognitive Function Under the Impact of Restraint Stress

2021 ◽  
Vol 14 ◽  
Author(s):  
Emil Trofimiuk ◽  
Przemysław Wielgat ◽  
Halina Car
Keyword(s):  
Spatial Memory ◽  
Restraint Stress ◽  
Reference Memory ◽  
Control Group ◽  
Memory Impairments ◽  
Spatial Reference ◽  
Spatial Reference Memory ◽  
Pre Treatment ◽  
New Compounds ◽  
The Impact

Background: A considerable number of competitive antagonists/inverse agonists of histamine H3 receptor (H3R) have progressed to clinical assessment, with pitolisant approved for the treatment of narcolepsy. H3R, highly expressed in the CNS, is regarded as a relevant target in CNS disorders. At the same time, new compounds including ABT-239 H3R antagonist (ABT; benzonitrile, 4-[2-[2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl]-5-benzofuranyl]-) are continually being tested. The study aimed to test ABT-239 as a prophylactic agent in stress-induced memory impairments.Methods: Stressed and non-stressed rats were pre-treated with ABT-239 and subsequently subjected to several behavioral tests aimed at assessing the animals’ working and spatial reference memory [Morris water maze (MWM), Barnes maze (BM)], assessing the locomotor function and anxiety-like behavior [Open field (OF), elevated “plus” maze—EPM].Results: Chronically stressed rats displayed a significant decline in spatial (working and reference) memory. In the MWM test, we observed an improvement in spatial reference memory in stressed animals and a positive after ABT-239 pre-treatment. In the BM test, the effect of ABT-239 administration on spatial memory changed in successive attempts, from negative initially to favorable in subsequent attempts, and negative in the last trial of the test in the control group of rats. However, a beneficial effect is noted in the group of stressed animals, which remained throughout the entire testing period.Conclusions: Presented findings demonstrate that ABT-239 shows the potential to abolish or prevent restraint stress-induced spatial memory impairments and cognitive deficits. However, in conditions of appetitive modulation, it could increase damage to memory (unstressed animals).

scholarly journals Role of designed Bio-Geometrical forms in antagonizing neurobehavioral burden of Wi-Fi radiation: Evidence-based experimental study

2019 ◽  
Vol 12 (3) ◽  
pp. 1217-1234
Author(s):  
Nevin E. Sharaf ◽  
Asmaa F. Galal ◽  
Mohamed S. El-Sawy ◽  
Aziza B. Shalby ◽  
Alaa H. Sayed ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Memory Task ◽  
Anxiety Level ◽  
Control Group ◽  
Hsp 70 ◽  
Brain Areas ◽  
Wireless Router ◽  
Geometrical Shapes ◽  
The Impact

This study investigated the impact of Wi-Fi signals exposure on cognitive function and its relevant brain biomarkers and the possible role of designed Bio-Geometrical forms in restoring the neurobehavioral alterations resulting from the exposure to the emerging radiation.Rats were assigned into 3 groups; Gp I control group (away from exposure to radiation); Gp II, III were exposed to wireless router signals for 24 h for 6 months and Gp III was protected by a set of designed BioGeometrical shapes. Animals were tested for spatial memory, anxiety and emotionality in addition to the related neurotransmitters (dopamine, serotonin and acetylcholine) in different brain areas. Melatonin, Heat Shock Protein (HSP-70) and acetylcholine esterase (AchE) were also measured in various brain regions and histopathological examination was carried out as well. Wi-Fi radiation exposed group showed elevated anxiety level and impaired spatial memory. Moreover, significant decline in dopamine, serotonin and acetylcholine levels in the investigated brain areas has been recorded. Melatonin levels were decreased in the cortex, striatum and hippocampus while HSP-70 was depleted in the cortex only. Using Bio-Geometrical forms along with Wi-Fi exposure could combat the burden of Wi-Fi radiation. This was evidenced by the recovery of the anxiety level and the improvement of memory task. In addition, the presence of Bio-Geometrical shapes could retrieve dopamine, serotonin and acetylcholine as well as melatonin and HSP-70 levels This study provides solid foundation for the potential use of Bio-Geometrical shapes to modify the insult of Wi-Fi radiation on brain function and structure.

Sign in / Sign up

Export Citation Format

Share Document