scholarly journals Immature Dentate Gyrus: An Endophenotype of Neuropsychiatric Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-24 ◽  
Author(s):  
Hideo Hagihara ◽  
Keizo Takao ◽  
Noah M. Walton ◽  
Mitsuyuki Matsumoto ◽  
Tsuyoshi Miyakawa
Keyword(s):  
Dentate Gyrus ◽  
Neuropsychiatric Disorders ◽  
Emotional Behavior ◽  
Knockout Mutant ◽  
Potential Implication ◽  
Behavioral Abnormalities ◽  
Normal Cognitive Function ◽  
Chronic Fluoxetine ◽  
Almost All ◽  
Abnormal Behaviors

Adequate maturation of neurons and their integration into the hippocampal circuit is crucial for normal cognitive function and emotional behavior, and disruption of this process could cause disturbances in mental health. Previous reports have shown that mice heterozygous for a null mutation inα-CaMKII, which encodes a key synaptic plasticity molecule, display abnormal behaviors related to schizophrenia and other psychiatric disorders. In these mutants, almost all neurons in the dentate gyrus are arrested at a pseudoimmature state at the molecular and electrophysiological levels, a phenomenon defined as “immature dentate gyrus (iDG).” To date, the iDG phenotype and shared behavioral abnormalities (including working memory deficit and hyperlocomotor activity) have been discovered in Schnurri-2 knockout, mutant SNAP-25 knock-in, and forebrain-specific calcineurin knockout mice. In addition, both chronic fluoxetine treatment and pilocarpine-induced seizures reverse the neuronal maturation, resulting in the iDG phenotype in wild-type mice. Importantly, an iDG-like phenomenon was observed in post-mortem analysis of brains from patients with schizophrenia/bipolar disorder. Based on these observations, we proposed that the iDG is a potential endophenotype shared by certain types of neuropsychiatric disorders. This review summarizes recent data describing this phenotype and discusses the data’s potential implication in elucidating the pathophysiology of neuropsychiatric disorders.

scholarly journals Housing Complexity Alters GFAP-Immunoreactive Astrocyte Morphology in the Rat Dentate Gyrus

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Garrick Salois ◽  
Jeffrey S. Smith
Keyword(s):  
Dentate Gyrus ◽  
Dendritic Spines ◽  
Morphological Changes ◽  
Sensory Stimulation ◽  
Confocal Imaging ◽  
Branch Points ◽  
Substantial Evidence ◽  
Rodent Brain ◽  
Behavioral Abnormalities ◽  
Enriched Environments

Rats used in research are typically housed singly in cages with limited sensory stimulation. There is substantial evidence that housing rats in these conditions lead to numerous neuroanatomical and behavioral abnormalities. Alternatively, rats can be housed in an enriched environment in which rats are housed in groups and given room for exercise and exploration. Enriched environments result in considerable neuroplasticity in the rodent brain. In the dentate gyrus of the hippocampus, enriched environments evoke especially profound neural changes, including increases in the number of neurons and the number of dendritic spines. However, whether changes in astrocytes, a type of glia increasingly implicated in mediating neuroplasticity, are concurrent with these neural changes remains to be investigated. In order to assess morphological changes among astrocytes of the rat dentate gyrus, piSeeDB was used to optically clear 250 μm sections of tissue labeled using GFAP immunohistochemistry. Confocal imaging and image analysis were then used to measure astrocyte morphology. Astrocytes from animals housed in EE demonstrated a reduced distance between filament branch points. Furthermore, the most complex astrocytes were significantly more complex among animals housed in EE compared to standard environments.

scholarly journals Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABAA and GABAB Receptors

2020 ◽  
Vol 21 (9) ◽  
pp. 3184
Author(s):  
Hana Kubová ◽  
Zdeňka Bendová ◽  
Simona Moravcová ◽  
Dominika Pačesová ◽  
Luisa Rocha ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Receptor Binding ◽  
Brain Structure ◽  
Gabab Receptor ◽  
Brain Structures ◽  
Emotional Behavior ◽  
Gabab Receptors ◽  
Behavioral Impairment ◽  
Almost All ◽  
The Brain

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life; however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP; 1 mg/kg/day) in 7–11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABAA receptor subunits (α1, α2, α4, γ2, and δ) and the GABAB B2 subunit, and GABAA, benzodiazepine, and GABAB receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the α2 subunit was upregulated, whereas that of the δ subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the α4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABAA receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABAB receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.

scholarly journals Ether Lipid Deficiency in Mice Produces a Complex Behavioral Phenotype Mimicking Aspects of Human Psychiatric Disorders

2019 ◽  
Vol 20 (16) ◽  
pp. 3929 ◽  
Author(s):  
Fabian Dorninger ◽  
Anna Gundacker ◽  
Gerhard Zeitler ◽  
Daniela D. Pollak ◽  
Johannes Berger
Keyword(s):  
Psychiatric Disorders ◽  
Treatment Strategies ◽  
Ether Lipid ◽  
Detailed Examination ◽  
Behavioral Phenotype ◽  
Emotional Behavior ◽  
Mental Illnesses ◽  
Ether Lipids ◽  
Behavioral Abnormalities ◽  
Deficient Mice

Ether lipids form a specialized subgroup of phospholipids that requires peroxisomes to be synthesized. We have previously detected that deficiency in these lipids leads to a severe disturbance of neurotransmitter homeostasis and release as well as behavioral abnormalities, such as hyperactivity, in a mouse model. Here, we focused on a more detailed examination of the behavioral phenotype of ether lipid-deficient mice (Gnpat KO) and describe a set of features related to human psychiatric disorders. Gnpat KO mice show strongly impaired social interaction as well as nestlet shredding and marble burying, indicating disturbed execution of inborn behavioral patterns. Also, compromised contextual and cued fear conditioning in these animals suggests a considerable memory deficit, thus potentially forming a connection to the previously determined ether lipid deficit in human patients with Alzheimer’s disease. Nesting behavior and the preference for social novelty proved normal in ether lipid-deficient mice. In addition, we detected task-specific alterations in paradigms assessing depression- and anxiety-related behavior. The reported behavioral changes may be used as easy readout for the success of novel treatment strategies against ether lipid deficiency in ameliorating nervous system-associated symptoms. Furthermore, our findings underline that ether lipids are paramount for brain function and demonstrate their relevance for cognitive, social, and emotional behavior. We hereby substantially extend previous observations suggesting a link between deficiency in ether lipids and human mental illnesses, particularly autism and attention-deficit hyperactivity disorder.

scholarly journals Compliance of Oral Snuff (Naswar) Packaging and Sales Practices with National Tobacco Control Laws and the Relevant Articles of Framework Convention on Tobacco Control in Khyber Pakhtunkhwa Pakistan

2020 ◽  
Vol 22 (12) ◽  
pp. 2224-2230
Author(s):  
Fayaz Ahmad ◽  
Zohaib Khan ◽  
Kamran Siddiqi ◽  
Muhammad Naseem Khan ◽  
Melanie Boeckman ◽  
...  
Keyword(s):  
Tobacco Control ◽  
Statistical Tests ◽  
Sampling Strategy ◽  
General Point ◽  
Cluster Sampling ◽  
Cross Sectional ◽  
Control Laws ◽  
Potential Implication ◽  
Health Warning ◽  
Almost All

Abstract Introduction Smokeless tobacco (SLT) is a significant contributor to tobacco-related harm in Pakistan but its control has lags behind that of combustible tobacco. We assessed the compliance of Naswar’s (a widely used SLT product in the Southeast Asia) packaging and sales practices with the national legislations and relevant articles of the WHO framework convention on tobacco control (FCTC). Aims and Methods A cross-sectional observational audit was conducted in three districts of Pakistan. We recruited 286 general point of sale (GPOS) and exclusive Naswar sellers (ENS) through a multistage cluster sampling strategy. Data were gathered on packaging and labeling practices of Naswar and advertisement and promotion practices inside and outside the shops. Statistical tests for association between the dependent variable-advertisement practices, and independent variables-area and vendor types were conducted. Results We analyzed 133 and 49 unique Naswar products sold in 229 GPOS and by 57 ENS, respectively. None of the local products had any written or pictorial health warning. More than half of retailers used one or two methods of advertising Naswar inside the shops while only 9% advertised outside the shops. ENS were more likely to be noncompliant with tobacco advertisement and promotion compared with GPOS. Conclusions The study presents first insights on the compliance of Naswar packaging and sale practices with local regulations and WHO FCTC provisions in Pakistan. Almost all products were on display in the shops and none of the local products had any health warning or contents disclosure on the packages. Implications Naswar is a form of SLT used extensively in Pakistan, Central Asia, and Pashtun populations across the globe. This study provides an important insight into the Naswar retail environment in a geographical setting where the use of Naswar is endemic. The study brings to fore previously unreported issues like an urban–rural disparity, and differences between exclusive and nonENS, with regards to Naswar advertisement and promotion. These findings have potential implication on the implementation of tobacco control retail policies. The lack of health warnings and free display of Naswar brands call for alignment of tobacco control efforts with the FCTC.

scholarly journals The Role of Dentate Gyrus Neurogenesis in Neuropsychiatric Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
M. Julia García-Fuster ◽  
Justin S. Rhodes ◽  
Chitra D. Mandyam
Keyword(s):  
Dentate Gyrus ◽  
Neuropsychiatric Disorders

scholarly journals Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147307 ◽  
Author(s):  
Yosuke Kitahara ◽  
Keisuke Ohta ◽  
Hiroshi Hasuo ◽  
Takahide Shuto ◽  
Mahomi Kuroiwa ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Perforant Path ◽  
Chronic Fluoxetine

scholarly journals Novel Role for the Streptococcus pneumoniae Toxin Pneumolysin in the Assembly of Biofilms

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Joshua R. Shak ◽  
Herbert P. Ludewick ◽  
Kristen E. Howery ◽  
Fuminori Sakai ◽  
Hong Yi ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Hemolytic Activity ◽  
Biofilm Formation ◽  
Early Time ◽  
Wild Type ◽  
Knockout Mutant ◽  
Content Type ◽  
Biofilm Development ◽  
Almost All

ABSTRACTStreptococcus pneumoniaeis an important commensal and pathogen responsible for almost a million deaths annually in children under five. The formation of biofilms byS. pneumoniaeis important in nasopharyngeal colonization, pneumonia, and otitis media. Pneumolysin (Ply) is a toxin that contributes significantly to the virulence ofS. pneumoniaeand is an important candidate as a serotype-independent vaccine target. Having previously demonstrated that aluxSknockout mutant was unable to form early biofilms and expressed lessplymRNA than the wild type, we conducted a study to investigate the role of Ply in biofilm formation. We found that Ply was expressed in early phases of biofilm development and localized to cellular aggregates as early as 4 h postinoculation.S. pneumoniae plyknockout mutants in D39 and TIGR4 backgrounds produced significantly less biofilm biomass than wild-type strains at early time points, both on polystyrene and on human respiratory epithelial cells, cultured under static or continuous-flow conditions. Ply’s role in biofilm formation appears to be independent of its hemolytic activity, asS. pneumoniaeserotype 1 strains, which produce a nonhemolytic variant of Ply, were still able to form biofilms. Transmission electron microscopy of biofilms grown on A549 lung cells using immunogold demonstrated that Ply was located both on the surfaces of pneumococcal cells and in the extracellular biofilm matrix. Altogether, our studies demonstrate a novel role for pneumolysin in the assembly ofS. pneumoniaebiofilms that is likely important during both carriage and disease and therefore significant for pneumolysin-targeting vaccines under development.IMPORTANCEThe bacteriumStreptococcus pneumoniae(commonly known as the pneumococcus) is commonly carried in the human nasopharynx and can spread to other body sites to cause disease. In the nasopharynx, middle ear, and lungs, the pneumococcus forms multicellular surface-associated structures called biofilms. Pneumolysin is an important toxin produced by almost allS. pneumoniaestrains, extensively studied for its ability to cause damage to human tissue. In this paper, we demonstrate that pneumolysin has a previously unrecognized role in biofilm formation by showing that strains without pneumolysin are unable to form the same amount of biofilm on plastic and human cell substrates. Furthermore, we show that the role of pneumolysin in biofilm formation is separate from the hemolytic activity responsible for tissue damage during pneumococcal diseases. This novel role for pneumolysin suggests that pneumococcal vaccines directed against this protein should be investigated for their potential impact on biofilms formed during carriage and disease.

scholarly journals Neuroinflammation induction and alteration of hippocampal neurogenesis in mice following developmental exposure to gossypol

2020 ◽  
Author(s):  
Xiaoyan Zhu ◽  
Yongji Wu ◽  
Jiarong Pan ◽  
Cixia Li ◽  
Jian Huang ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Developmental Stages ◽  
Critical Role ◽  
Perinatal Period ◽  
Hippocampal Neurogenesis ◽  
Experimental Conditions ◽  
Radial Glial Cells ◽  
Behavioral Abnormalities ◽  
Proliferation And Differentiation

Abstract Background Neurogenesis in the neonatal period involves the proliferation and differentiation of neuronal stem/progenitor cells, and the establishment of synaptic connections. This process plays a critical role in determining the normal development and maturation of the brain throughout life. Exposure to certain physical or chemical factors during the perinatal period can lead to a great deal of neuropathological defects that cause high cognitive dysfunction are accompanied by abnormal hippocampal neurogenesis and plasticity. As an endocrine disruptor, gossypol is generally known to exert detrimental effects in animals exposed under experimental conditions. However, it is unclear whether gossypol affects neurogenesis in the hippocampal dentate gyrus during early developmental stages. Methods Pregnant ICR mice were treated with gossypol at a daily dose of 0, 20 and 50 mg/kg body weight from embryonic day 6.5 to postnatal day (P) 21. The changes of hippocampal neurogenesis as well as potential mechanisms were investigated by 5-bromo-2-deoxyuridine labeling, behavioral tests, immunofluorescence, quantitative RT-PCR and Western blot analyses. Results At P8, maternal gossypol exposure impaired neural stem cell proliferation in the dentate gyrus, and decreased the number of newborn cells as a result of reduced proliferation of BLBP + radial glial cells and Tbr2 + intermediate progenitor cells. At P21, the numbers of NeuN + neurons and parvalbumin + γ-aminobutyric acid (GABA)ergic interneurons were increased following 50 mg/kg gossypol exposure. In addition, gossypol induced hippocampal neuroinflammation, which may contribute to behavioral abnormalities and cognitive deficits, and decrease synaptic plasticity. Conclusions Our findings suggest that developmental gossypol exposure affects hippocampal neurogenesis by targeting the proliferation and differentiation of neuronal stem/progenitor cells, cognitive functions, along with neuroinflammation. The present data provide novel insights into the neurotoxic effects of gossypol on offspring.

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