Subchronic neurotoxicity of diazinon in albino mice: Impact of oxidative stress, AChE activity, and gene expression disturbances in the cerebral cortex and hippocampus on mood, spatial learning, and memory function

We tested the hypothesis that excess saturated fat consumption during pregnancy, lactation, and/or postweaning alters the expression of genes mediating hippocampal synaptic efficacy and impairs spatial learning and memory in adulthood. Dams were fed control chow or a diet high in saturated fat before mating, during pregnancy, and into lactation. Offspring were weaned to either standard chow or a diet high in saturated fat. The Morris Water Maze was used to evaluate spatial learning and memory. Open field testing was used to evaluate motor activity. Hippocampal gene expression in adult males was measured using RT-PCR and ELISA. Offspring from high fat-fed dams took longer, swam farther, and faster to try and find the hidden platform during the 5-day learning period. Control offspring consuming standard chow spent the most time in memory quadrant during the probe test. Offspring from high fat-fed dams consuming excess saturated fat spent the least. The levels of mRNA and protein for brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein were significantly decreased by maternal diet effects. Nerve growth factor mRNA and protein levels were significantly reduced in response to both maternal and postweaning high-fat diets. Expression levels for the N-methyl-d-aspartate receptor (NMDA) receptor subunit NR2B as well as synaptophysin were significantly decreased in response to both maternal and postweaning diets. Synaptotagmin was significantly increased in offspring from high fat-fed dams. These data support the hypothesis that exposure to excess saturated fat during hippocampal development is associated with complex patterns of gene expression and deficits in learning and memory.

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Nrf2 Ablation Promotes Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3050971 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Peng Ren ◽

Jingwei Chen ◽

Bingxuan Li ◽

Mengzhou Zhang ◽

Bei Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Learning And Memory ◽

Spatial Learning ◽

Morris Water Maze Test ◽

Spatial Learning And Memory ◽

Related Factor ◽

Qrt Pcr

Introduction. Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) peptide and hyperphosphorylated tau protein. Accumulating evidence has revealed that the slow progressive deterioration of AD is associated with oxidative stress and chronic inflammation in the brain. Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2), which acts through the Nrf2/ARE pathway, is a key regulator of the antioxidant and anti-inflammatory response. Although recent data show a link between Nrf2 and AD-related cognitive decline, the mechanism is still unknown. Thus, we explored how Nrf2 protects brain cells against the oxidative stress and inflammation of AD in a mouse model of AD (APP/PS1 transgenic (AT) mice) with genetic removal of Nrf2. Methods. The spatial learning and memory abilities of 12-month-old transgenic mice were evaluated using a Morris water maze test. Hippocampal levels of Nrf2, Aβ, and p-tauS404 and of astrocytes and microglia were determined by immunostaining. Inflammatory cytokines were determined by ELISA and quantitative real-time polymerase chain reaction (qRT-PCR). Oxidative stress was measured by 8-hydroxydeoxyguanosine immunohistochemistry, and the antioxidant response was determined by qRT-PCR. Results. The spatial learning and memory abilities of AT mice were impaired after Nrf2 deletion. Aβ and p-tauS404 accumulation was increased in the hippocampus of AT/Nrf2-KO mice. Astroglial and microglial activation was exacerbated, followed by upregulation of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. Conclusion. Our present results show that Nrf2 deficiency aggravates AD-like pathology in AT mice. This phenotype was associated with increased levels of oxidative and proinflammatory markers, which suggests that the Nrf2 pathway may be a promising therapeutic target for AD.

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Improvement of spatial learning and memory, cortical gyrification patterns and brain oxidative stress markers in diabetic rats treated with Ficus deltoidea leaf extract and vitexin

Journal of Traditional and Complementary Medicine ◽

10.1016/j.jtcme.2017.05.006 ◽

2018 ◽

Vol 8 (1) ◽

pp. 190-202 ◽

Cited By ~ 16

Author(s):

S. Nurdiana ◽

Y.M. Goh ◽

A. Hafandi ◽

S.M. Dom ◽

A. Nur Syimal'ain ◽

...

Keyword(s):

Oxidative Stress ◽

Learning And Memory ◽

Spatial Learning ◽

Leaf Extract ◽

Diabetic Rats ◽

Spatial Learning And Memory ◽

Oxidative Stress Markers ◽

Ficus Deltoidea ◽

Stress Markers ◽

Brain Oxidative Stress

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Effects of subchronic benzo(a)pyrene exposure on neurotransmitter receptor gene expression in the rats hippocampus related with spatial learning and memory change

Toxicology ◽

10.1016/j.tox.2011.07.012 ◽

2011 ◽

Vol 289 (2-3) ◽

pp. 83-90 ◽

Cited By ~ 20

Author(s):

Chongying Qiu ◽

Shuqun Cheng ◽

Yinyin Xia ◽

Bin Peng ◽

Qian Tang ◽

...

Keyword(s):

Gene Expression ◽

Learning And Memory ◽

Spatial Learning ◽

Receptor Gene ◽

Spatial Learning And Memory ◽

Neurotransmitter Receptor ◽

Memory Change ◽

Receptor Gene Expression

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Milk Exosomes Cross the Blood-Brain Barrier in Murine Cerebral Cortex Endothelial Cells and Promote Dendritic Complexity in the Hippocampus and Brain Function in C57BL/6J Mice

10.1101/2021.11.24.469889 ◽

2021 ◽

Author(s):

Fang Zhou ◽

Pearl Ebea ◽

Ezra Mutai ◽

Sonal Sukreet ◽

Shya Navazesh ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Brain Development ◽

Learning And Memory ◽

Kainic Acid ◽

Spatial Learning ◽

Granule Cells ◽

Spatial Learning And Memory ◽

Adult Mice ◽

Dendritic Complexity

Background: Human milk contains large amounts of exosomes (MEs) and their regulatory microRNA cargos, whereas infant formulas contain only trace amounts of MEs and microRNAs. Breastfeeding has been implicated in optimal brain development but experimental evidence linking ME intake with brain development is limited. Objectives: We assessed the transport of MEs across the blood-brain barrier (BBB) and ME accumulation in distinct regions of the brain in brain endothelial cells and suckling mice. We further assessed BME-dependent gene expression profiles and effects on the dendritic complexity of hippocampal granule cells and phenotypes of BME depletion in neonate, juvenile and adult mice. Methods: The transfer of MEs across the BBB was assessed by using bovine MEs labeled with FM4-64 or loaded with IRDye-labeled miR-34a in murine brain endothelial bEnd.3 cell monolayers and dual chamber systems, and in wild-type newborn pups fostered to exosome and cargo tracking (ECT) dams that express MEs endogenously labeled with a CD63-eGFP fusion protein for subsequent analysis by serial two-photon tomography and staining with anti-eGFP antibodies. Effects of MEs on gene expression and dendritic architecture of granule cells was analyzed in hippocampi from juvenile mice fed exosome and RNA-depleted (ERD) and exosome and RNA-sufficient (ERS) diets by using RNA-sequencing analysis and Golgi-Cox staining followed by integrated neuronal tracing and morphological analysis of neuronal dendrites, respectively. Spatial learning and severity of kainic acid-induced seizures were assessed in mice fed ERD and ERS diets. Results: bEnd.3 cells internalized MEs by using a saturable transport mechanism and secreted miR-34a across the basal membrane. MEs penetrated the entire brain in fostering experiments; major regions of accumulation included the hippocampus, cortex and cerebellum. Two hundred ninety-five genes were differentially expressed in hippocampi from male mice fed ERD and ERS diets; high-confidence gene networks included pathways implicated in axon guidance and calcium signaling. Only one gene was differentially expressed in females fed the experimental diets. Juvenile pups fed the ERD diet had reduced dendritic complexity of dentate granule cells in the hippocampus, scored nine-fold lower in the Barnes maze test of spatial learning and memory (P < 0.01), and the severity of seizures was 5-fold higher following kainic acid administration in adult mice fed the ERD diet compared to mice fed the ERS diet (P < 0.01). Conclusions: MEs cross the BBB and contribute toward optimal neuronal development, spatial learning and memory, and resistance to kainic acid-induced seizures in mice.

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Reelin Improves Cognition and Extends the Lifespan of Mutant Ndel1 Mice with Postnatal CA1 Hippocampus Deterioration

Cerebral Cortex ◽

10.1093/cercor/bhaa088 ◽

2020 ◽

Vol 30 (9) ◽

pp. 4964-4978 ◽

Cited By ~ 2

Author(s):

Ivana Kiroski ◽

Yulan Jiang ◽

Cezar Gavrilovici ◽

Fan Gao ◽

Sukyoung Lee ◽

...

Keyword(s):

Learning And Memory ◽

Spatial Learning ◽

Pyramidal Neurons ◽

Neurological Diseases ◽

Memory Function ◽

Neuronal Cell ◽

Adult Brain ◽

Conditional Knockout ◽

Spatial Learning And Memory ◽

Ca1 Pyramidal Neurons

Abstract The glycoprotein Reelin maintains neuronal positioning and regulates neuronal plasticity in the adult brain. Reelin deficiency has been associated with neurological diseases. We recently showed that Reelin is depleted in mice with a targeted disruption of the Ndel1 gene in forebrain postnatal excitatory neurons (Ndel1 conditional knockout (CKO)). Ndel1 CKO mice exhibit fragmented microtubules in CA1 pyramidal neurons, profound deterioration of the CA1 hippocampus and a shortened lifespan (~10 weeks). Here we report that Ndel1 CKO mice (of both sexes) experience spatial learning and memory deficits that are associated with deregulation of neuronal cell adhesion, plasticity and neurotransmission genes, as assessed by genome-wide transcriptome analysis of the hippocampus. Importantly, a single injection of Reelin protein in the hippocampus of Ndel1 CKO mice improves spatial learning and memory function and this is correlated with reduced intrinsic hyperexcitability of CA1 pyramidal neurons, and normalized gene deregulation in the hippocampus. Strikingly, when treated with Reelin, Ndel1 CKO animals that die from an epileptic phenotype, live twice as long as nontreated, or vehicle-treated CKO animals. Thus, Reelin confers striking beneficial effects in the CA1 hippocampus, and at both behavioral and organismal levels.

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Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway

Endocrine Connections ◽

10.1530/ec-18-0069 ◽

2018 ◽

Vol 7 (5) ◽

pp. 688-697 ◽

Cited By ~ 4

Author(s):

Fan Zhang ◽

Jian Chen ◽

Xinyue Lin ◽

Shiqiao Peng ◽

Xiaohui Yu ◽

...

Keyword(s):

Cerebral Cortex ◽

Learning And Memory ◽

Spatial Learning ◽

Subclinical Hypothyroidism ◽

Long Term Potentiation ◽

Neurotrophin Receptor ◽

Spatial Learning And Memory ◽

Overt Hypothyroidism ◽

P75 Neurotrophin Receptor ◽

Oh Groups

Objective Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH) on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring. Methods Female adult Wistar rats were randomly divided into three groups (n = 15 per group): control (CON) group, SCH group and overt hypothyroidism (OH) group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP) and Morris water-maze (MWM) test. The protein expression of the p75 neurotrophin receptor (p75NTR), phospho-c-Jun N-terminal kinase (p-JNK), the pro-apoptotic protein p53 and Bax were detected by Western blotting. Results The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75NTR, p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group. Conclusions Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex.

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