scholarly journals Hesperidin Alleviates Methotrexate-Induced Memory Deficits via Hippocampal Neurogenesis in Adult Rats

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 936 ◽  
Author(s):  
Salinee Naewla ◽  
Apiwat Sirichoat ◽  
Wanassanan Pannangrong ◽  
Pornthip Chaisawang ◽  
Peter Wigmore ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Memory Loss ◽  
Memory Deficits ◽  
Hippocampal Neurogenesis ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Ki 67 ◽  
Novel Object ◽  
Immature Neurons

Methotrexate (MTX), a folic acid antagonist, is widely used in cancer treatment. However, treatment with MTX reduces hippocampal neurogenesis, leading to memory deficits. Hesperidin (Hsd) is a flavonoid glycoside that promotes anti-inflammation, acts as an antioxidant, and has neuroprotective properties. Consumption of Hsd enhances learning and memory. In the present study, we investigated the protective effects of Hsd against MTX-induced impairments of memory and neurogenesis; male Sprague Dawley rats were administered with a single dose of MTX (75 mg/kg) by intravenous (i.v.) injection on days 8 and 15 or Hsd (100 mg/kg) by oral gavage for 21 days. Memory was tested using novel object location (NOL) and novel object recognition (NOR) tasks. Immunofluorescence staining of Ki-67, bromodeoxyuridine (BrdU), and doublecortin (DCX) was performed to assess cell proliferation, survival, and immature neurons. The data showed that Hsd and MTX did not disable locomotor ability. The MTX animals exhibited memory deficits in both memory tests. There were significant decreases in the numbers of cell proliferation, survival, and immature neurons in the MTX animals. However, co-administration with MTX and Hsd alleviated memory loss and neurogenesis decline. These results revealed that Hsd could protect against MTX side effects in the animals in this study.

scholarly journals Chrysin Protects against Memory and Hippocampal Neurogenesis Depletion in D-Galactose-Induced Aging in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1100
Author(s):  
Ram Prajit ◽  
Nataya Sritawan ◽  
Kornrawee Suwannakot ◽  
Salinee Naewla ◽  
Anusara Aranarochana ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Survival ◽  
Brain Aging ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Hippocampal Neurogenesis ◽  
Neuroprotective Effects ◽  
Ki 67 ◽  
Novel Object ◽  
Immature Neurons

The interruption of hippocampal neurogenesis due to aging impairs memory. The accumulation of D-galactose (D-gal), a monosaccharide, induces brain aging by causing oxidative stress and inflammation, resulting in neuronal cell damage and memory loss. Chrysin, an extracted flavonoid, has neuroprotective effects on memory. The present study aimed to investigate the effect of chrysin on memory and hippocampal neurogenesis in brains aged using D-gal. Male Sprague-Dawley rats received either D-gal (50 mg/kg) by i.p. injection, chrysin (10 or 30 mg/kg) by oral gavage, or D-gal (50 mg/kg) and chrysin (10 or 30 mg/kg) for 8 weeks. Memory was evaluated using novel object location (NOL) and novel object recognition (NOR) tests. Hippocampal neurogenesis was evaluated using Ki-67, 5-bromo-2′-deoxyuridine (BrdU), and doublecortin (DCX) immunofluorescence staining to determine cell proliferation, cell survival, and number of immature neurons, respectively. We found that D-gal administration resulted in memory impairment as measured by NOL and NOR tests and in depletions in cell proliferation, cell survival, and immature neurons. However, co-treatment with chrysin (10 or 30 mg/kg) attenuated these impairments. These results suggest that chrysin could potentially minimize memory and hippocampal neurogenesis depletions brought on by aging.

scholarly journals Hesperidin Reduces Memory Impairment Associated with Adult Rat Hippocampal Neurogenesis Triggered by Valproic Acid

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4364
Author(s):  
Anusara Aranarochana ◽  
Soraya Kaewngam ◽  
Tanaporn Anosri ◽  
Apiwat Sirichoat ◽  
Wanassanun Pannangrong ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Memory Impairment ◽  
Memory Loss ◽  
Hippocampal Neurogenesis ◽  
Immunofluorescent Staining ◽  
Ki 67 ◽  
Novel Object ◽  
Memory Impairments ◽  
Adult Rat ◽  
Behavioral Expression

Treatment with valproic acid (VPA) deteriorates hippocampal neurogenesis, which leads to memory impairment. Hesperidin (Hsd) is a plant-based bioflavonoid that can augment learning and memory. This study aimed to understand the effect of Hsd on the impairment of hippocampal neurogenesis and memory caused by VPA. The VPA (300 mg/kg) was administered by intraperitoneal injection twice daily for 14 days, and Hsd (100 mg/kg/day) was administered by oral gavage once a day for 21 days. All rats underwent memory evaluation using the novel object location (NOL) and novel object recognition (NOR) tests. Immunofluorescent staining of Ki-67, BrdU/NeuN, and doublecortin (DCX) was applied to determine hippocampal neurogenesis in cell proliferation, neuronal survival, and population of the immature neurons, respectively. VPA-treated rats showed memory impairments in both memory tests. These impairments resulted from VPA-induced decreases in the number of Ki-67-, BrdU/NeuN-, and DCX-positive cells in the hippocampus, leading to memory loss. Nevertheless, the behavioral expression in the co-administration group was improved. After receiving co-administration with VPA and Hsd, the numbers of Ki-67-, BrdU/NeuN-, and DCX-positive cells were improved to the normal levels. These findings suggest that Hsd can reduce the VPA-induced hippocampal neurogenesis down-regulation that results in memory impairments.

scholarly journals Protective effects of dietary fibre against manganese-induced neurobehavioral aberrations in rats

2012 ◽  
Vol 63 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Xiu-Quan Shi ◽  
Wei Yan ◽  
Ke-Yue Wang ◽  
Qi-Yuan Fan ◽  
Yan Zou
Keyword(s):  
Cerebral Cortex ◽  
Animal Feed ◽  
Oral Exposure ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Neurobehavioral Performance ◽  
Sprague Dawley Rats ◽  
Applied Dose ◽  
Mn Concentrations

We tested the hypothesis that dietary fi bre (DF) has protective effects against manganese (Mn)-induced neurotoxicity. Forty-eight one-month old Sprague-Dawley rats were randomly divided into six groups: control, 16 % DF, Mn (50 mg kg-1 body weight), Mn+ 4 % DF, Mn+ 8 % DF, and Mn+ 16 % DF. After oral administration of Mn (as MnCl2) by intragastric tube during one month, we determined Mn concentrations in the blood, liver, cerebral cortex, and stool and tested neurobehavioral functions. Administration of Mn was associated with increased Mn concentration in the blood, liver, and cerebral cortex and increased Mn excretion in the stool. Aberrations in neurobehavioral performance included increases in escape latency and number of errors and decrease in step-down latency. Irrespective of the applied dose, the addition of DF in forage decreased tissue Mn concentrations and increased Mn excretion rate in the stool by 20 % to 35 %. All neurobehavioral aberrations were also improved. Our fi ndings show that oral exposure to Mn may cause neurobehavioral abnormalities in adult rats that could be effi ciently alleviated by concomitant supplementation of DF in animal feed.

scholarly journals High-Fat Programming of Hyperglycemia, Hyperinsulinemia, Insulin Resistance, Hyperleptinemia, and Altered Islet Architecture in 3-Month-Old Wistar Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Marlon E. Cerf ◽  
Charna S. Chapman ◽  
Johan Louw
Keyword(s):  
Cell Proliferation ◽  
Acinar Cell ◽  
High Fat Diet ◽  
Alpha Cell ◽  
Postnatal Life ◽  
Fetal Life ◽  
High Fat ◽  
Cell Hyperplasia ◽  
Adult Rats ◽  
Ki 67

High-fat programming, by exposure to a high-saturated-fat diet in utero and/or during lactation, compromises beta-cell development and function in neonatal and weanling offspring. Therefore, high-fat programming effects were investigated on metabolism and islet architecture in young adult rats. Three-month-old male and female Wistar rat offspring were studied: HFG (maintained on a high-fat diet throughout fetal life), HFP (high-fat diet maintenance from birth to 3 months), and HFGP (high-fat diet maintenance throughout fetal and postnatal life). Control rats were maintained on a standard laboratory diet. Pancreata were double immunolabeled for insulin and glucagon to assess islet morphology and with Ki-67 to determine islet and acinar cell proliferation. HFP and HFGP males were heavier, hyperleptinemic, and hyperinsulinemic. Hyperglycemia presented in HFP males, HFP females, and HFGP males. HFGP males and HFP females were insulin resistant. HFP males displayed beta- and alpha-cell hyperplasia with alpha-cell hypertrophy evident in HFP females. Acinar cell proliferation rates were increased in HFP males. Postnatal high-fat programming induced the most diabetogenic phenotype with high-fat maintenance throughout fetal and postnatal life resulting in a severely obese phenotype. Fetal and postnatal nutrition shapes offspring health outcomes.

scholarly journals Neonatal and Juvenile Ocular Development in Sprague-Dawley Rats: A Histomorphological and Immunohistochemical Study

2017 ◽  
Vol 55 (2) ◽  
pp. 310-330 ◽  
Author(s):  
Vanessa Vrolyk ◽  
Julius Haruna ◽  
Marie-Odile Benoit-Biancamano
Keyword(s):  
Cell Proliferation ◽  
Morphological Changes ◽  
Harderian Gland ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Ocular Tissue ◽  
Sprague Dawley ◽  
Ki 67 ◽  
Rapid Phase ◽  
Free Zone ◽  
Sd Rats

As in many altricial species, rats are born with fused eyelids and markedly underdeveloped eyes. While the normal histology of the eyes of mature rats is known, the histomorphological changes occurring during postnatal eye development in this species remain incompletely characterized. This study was conducted to describe the postnatal development of ocular structures in Sprague-Dawley (SD) rats during the first month of age using histology and immunohistochemistry (IHC). Both eyes were collected from 51 SD rats at 13 time points between postnatal day (PND)1 and PND30. Histologic examination of hematoxylin and eosin-stained sections was performed, as well as IHC for cleaved-caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) to evaluate apoptosis, and IHC for Ki-67 and phospho-histone-H3 to evaluate cell proliferation. Extensive ocular tissue remodeling occurred prior to the eyelid opening around PND14 and reflected the interplay between apoptosis and cell proliferation. Apoptosis was particularly remarkable in the maturing subcapsular anterior epithelium of the lens, the inner nuclear and ganglion cell layers of the developing retina, and the Harderian gland, and was involved in the regression of the hyaloid vasculature. Nuclear degradation in the newly formed secondary lens fibers was noteworthy after birth and was associated with TUNEL-positive nuclear remnants lining the lens organelle-free zone. Cell proliferation was marked in the developing retina, cornea, iris, ciliary body and Harderian gland. The rat eye reached histomorphological maturity at PND21 after a rapid phase of morphological changes characterized by the coexistence of cell death and proliferation.

scholarly journals Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in the Hippocampus in an Adult Rat Model

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1053 ◽  
Author(s):  
Jariya Welbat ◽  
Pornthip Chaisawang ◽  
Wanassanun Pannangrong ◽  
Peter Wigmore
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Centella Asiatica ◽  
Memory Deficits ◽  
Cell Number ◽  
Hippocampal Neurogenesis ◽  
Related Factor ◽  
Asiatic Acid ◽  
Sprague Dawley ◽  
Chemotherapy Drugs

5-fluorouracil or 5-FU (a chemotherapeutic medication) has been revealed to induce memory deficits in many cancer patients. Asiatic acid (AA) is a triterpenoid extract from Centella asiatica. This compound can ameliorate intracellular oxidative stress caused by chemotherapy drugs. Recent studies have shown that AA is capable of inhibiting neuronal generation and memory deficit produced by 5-FU chemotherapy. This study aimed to assess the molecular mechanisms of AA related to hippocampal neurogenesis and memory in rats receiving 5-FU. Male Sprague Dawley rats were given AA (30 mg/kg) orally and given 5-FU (25 mg/kg) by i.v. injection 5 times. Some rats were given AA for 20 days before and during 15-FU treatment (preventive), some received AA for 20 days after 5-FU treatment (recovery), and some underwent treatment with AA throughout the time of the experiment (throughout) for 40 days. Treatment with 5-FU caused significant reductions in Notch1, sex determining region Y-box 2 (SOX2), nestin, doublecortin (DCX), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels within the hippocampus. In addition, 5-FU significantly increased p21 positive cell number in the subgranular zone (SGZ) and malondialdehyde (MDA) levels in the hippocampus. Administration with both AA and 5-FU in prevention and throughout was able to prevent decreases in Notch1 SOX2, nestin, DCX, and Nrf2 caused by 5-FU. Treatment with AA also led to decreases in p21 positive cells and MDA levels in the hippocampus. These findings exhibit that AA has the ability to counteract the down-regulation of neurogenesis within the hippocampus and memory deficits caused by 5-FU via inhibiting oxidative stress and increasing neuroprotective properties.

scholarly journals Protective Effects of Genistein against Mono-(2-ethylhexyl) Phthalate-Induced Oxidative Damage in Prepubertal Sertoli Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Liandong Zhang ◽  
Ming Gao ◽  
Tongdian Zhang ◽  
Tie Chong ◽  
Ziming Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cells ◽  
Endocrine Disrupting Chemicals ◽  
Protective Effects ◽  
Proliferation Inhibition ◽  
Inhibition Rate ◽  
Sprague Dawley ◽  
Necrosis Rate ◽  
Cell Proliferation Inhibition ◽  
Ethylhexyl Phthalate

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein are two of the most prevalent endocrine-disrupting chemicals (EDCs) that present in the environment and food. However, how these two EDCs would affect prepubertal Sertoli cells development was rarely studied. In this study, primary prepubertal Sertoli cells were isolated from 22-day-old Sprague Dawley rats and exposed to MEHP at 1 μmol/L, 10 μmol/L, and 100 μmol/L (M1, M10, and M100), genistein at 10 μmol/L (G), and their combination (G + M1, G + M10, and G + M100). Cell proliferation inhibition rate, apoptosis and necrosis rate, and cellular redox state were evaluated. Our results revealed that MEHP could significantly increase cell proliferation inhibition rate, apoptosis rate, necrosis rate, and intracellular reactive oxidative species level. However, coadministration of genistein could partially alleviate MEHP-induced prepubertal Sertoli cells oxidative injuries via enhancement of testicular antioxidative enzymes activities and upregulation of Nrf2 and HO-1, indicating that genistein could partially attenuate MEHP-induced prepubertal Sertoli cells damage through antioxidative action and may have promising future on its curative role for attenuating other EDCs-induced reproductive disorders.

scholarly journals Effects of estrogen on cerebrovascular function: age-dependent shifts from beneficial to detrimental in small cerebral arteries of the rat

2016 ◽  
Vol 310 (10) ◽  
pp. H1285-H1294 ◽  
Author(s):  
Rachel R. Deer ◽  
John N. Stallone
Keyword(s):  
Cerebral Arteries ◽  
Protective Effects ◽  
Estrogen Replacement ◽  
Sprague Dawley ◽  
Vascular Effects ◽  
Adult Rats ◽  
Exogenous Estrogen ◽  
Cerebrovascular Function ◽  
Sprague Dawley Rats ◽  
Age Dependent

In the present study, interactions of age and estrogen in the modulation of cerebrovascular function were examined in small arteries <150 μM. The hypothesis tested was that age enhances deleterious effects of exogenous estrogen by augmenting constrictor prostanoid (CP)-potentiated reactivity of the female (F) cerebrovasculature. F Sprague-Dawley rats approximating key stages of “hormonal aging” in humans were studied: perimenopausal (mature multi-gravid, MA, cyclic, 5–6 mo of age) and postmenopausal (reproductively senescent, RS, acyclic 10–12 mo of age). Rats underwent bilateral ovariectomy and were given estrogen replacement therapy (E) or placebo (O) for 14–21 days. Vasopressin reactivity (VP, 10−12–10−7 M) was measured in pressurized middle cerebral artery segments, alone or in the presence of COX-1- (SC560, 1 μM) or COX-2- (NS398, 10 μM) selective inhibitors. VP-stimulated release of prostacyclin (PGI2) and thromboxane (TXA2) were assessed by radioimmunoassay of 6-keto-PGF1α and TXB2 (stable metabolites). VP-induced vasoconstriction was attenuated in ovariectomized + estrogen-replaced, multigravid adult rats (5–6 mo; MAE) but potentiated in older ovariectomized + estrogen-replaced, reproductively senescent rats (12–14 mo; RSE). SC560 and NS398 reduced reactivity similarly in ovariectomized multigravid adult rats (5–6 mo; MAO) and ovariectomized reproductively senescent rat (12–14 mo; RSO). In MAE, reactivity to VP was reduced to a greater extent by SC560 than by NS398; however, in RSE, this effect was reversed. VP-stimulated PGI2 was increased by estrogen, yet reduced by age. VP-stimulated TXA2 was increased by estrogen and age in RSE but did not differ in MAO and RSO. Taken together, these data reveal that the vascular effects of estrogen are distinctly age-dependent in F rats. In younger MA, beneficial and protective effects of estrogen are evident (decreased vasoconstriction, increased dilator prostanoid function). Conversely, in older RS, detrimental effects of estrogen begin to be manifested (enhanced vasoconstriction and CP function). These findings may lead to age-specific estrogen replacement therapies that maximize beneficial and minimize detrimental effects of this hormone on small cerebral arteries that regulate blood flow. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/effects-of-age-and-estrogen-on-cerebrovascular-function/ .

scholarly journals Chronic Lorcaserin Treatment Reverses the Nicotine Withdrawal-Induced Disruptions to Behavior and Maturation in Developing Neurons in the Hippocampus of Rats

2021 ◽  
Vol 22 (2) ◽  
pp. 868
Author(s):  
Magdalena Zaniewska ◽  
Agnieszka Nikiforuk ◽  
Urszula Głowacka ◽  
Sabina Brygider ◽  
Julita Wesołowska ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Brain Slices ◽  
Recognition Task ◽  
Nicotine Withdrawal ◽  
Hippocampal Neurogenesis ◽  
Sprague Dawley ◽  
Self Administration ◽  
Ki 67 ◽  
Locomotor Hyperactivity ◽  
Immobility Time

Preclinical data have shown that treatment with serotonin (5-HT)2C receptor agonists inhibits the behavioral effects of nicotine, including self-administration, reinstatement, and locomotor responses to nicotine. Since the data on the effects of 5-HT2C receptor agonism on nicotine withdrawal signs are limited, we aimed to investigate whether 5-HT2C receptor agonism alleviated the behavioral and neurobiochemical (hippocampal neurogenesis) consequences of nicotine withdrawal in Sprague-Dawley rats. Our data indicate that withdrawal from nicotine self-administration induced locomotor hyperactivity, lengthened immobility time (the forced swim test), induced ‘drug-seeking’ behavior and deficits in cognition-like behavior (the novel object recognition task). A two-week exposure to the 5-HT2C receptor agonist lorcaserin attenuated locomotor hyperactivity and induced recovery from depression-like behavior. Analyses of brain slices from nicotine-withdrawn animals revealed that lorcaserin treatment recovered the reduced number of doublecortin (DCX)-positive cells, but it did not affect the number of Ki-67- or 5-bromo-2’-deoxyuridine (BrdU)-positive cells or the maturation of proliferating neurons in drug-weaned rats. To summarize, we show that lorcaserin alleviated locomotor responses and depression-like state during nicotine withdrawal. We propose that the modulatory effect of lorcaserin on the ‘affective’ aspects of nicotine cessation may be linked to the positive changes caused by the compound in hippocampal neurogenesis during nicotine withdrawal.

scholarly journals Prepubertal Exposure to Genistein Alleviates Di-(2-ethylhexyl) Phthalate Induced Testicular Oxidative Stress in Adult Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lian-Dong Zhang ◽  
He-Cheng Li ◽  
Tie Chong ◽  
Ming Gao ◽  
Jian Yin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Environmental Endocrine Disruptors ◽  
Sprague Dawley Rats ◽  
Antioxidative Effects ◽  
Testicular Histology ◽  
Ethylhexyl Phthalate

Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.

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