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15 pages, 7230 KiB

Open AccessArticle

Sex Differences between Neuronal Loss and the Early Onset of Amyloid Deposits and Behavioral Consequences in 5xFAD Transgenic Mouse as a Model for Alzheimer’s Disease

by Chi Him Poon, San Tung Nicholas Wong, Jaydeep Roy, Yingyi Wang, Hui Wang Hujo Chan, Harry Steinbusch, Arjan Blokland, Yasin Temel, Luca Aquili and Lee Wei Lim

Cells 2023, 12(5), 780; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12050780 - 01 Mar 2023

Cited by 7 | Viewed by 2473

Abstract

A promising direction in the research on Alzheimer’s Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal [...] Read more.

A promising direction in the research on Alzheimer’s Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal loss could better inform cognitive impairment. We have utilised the 5xFAD transgenic mouse model that displays AD pathology at an early phase, already fully manifested after 6 months. We have evaluated the relationships between cognitive impairment, amyloid deposition, and neuronal loss in the hippocampus in both male and female mice. We observed the onset of disease characterized by the emergence of cognitive impairment in 6-month-old 5xFAD mice coinciding with the emergence of neuronal loss in the subiculum, but not amyloid pathology. We also showed that female mice exhibited significantly increased amyloid deposition in the hippocampus and entorhinal cortex, highlighting sex-related differences in the amyloid pathology of this model. Therefore, parameters based on neuronal loss might more accurately reflect disease onset and progression compared to amyloid-based biomarkers in AD patients. Moreover, sex-related differences should be considered in studies involving 5xFAD mouse models. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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20 pages, 10562 KiB

Open AccessArticle

Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome

by Silvia Giannoccaro, Celeste Ferraguto, Valeria Petroni, Coline Marcelly, Xavier Nogues, Victoria Campuzano and Susanna Pietropaolo

Cells 2023, 12(3), 391; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12030391 - 21 Jan 2023

Cited by 1 | Viewed by 1688

Abstract

Williams–Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of [...] Read more.

Williams–Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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16 pages, 4181 KiB

Open AccessArticle

Pregestational Exposure to T. gondii Produces Maternal Antibodies That Recognize Fetal Brain Mimotopes and Induces Neurochemical and Behavioral Dysfunction in the Offspring

by Eunice Romero Núñez, Tonali Blanco Ayala, Gustavo Ignacio Vázquez Cervantes, Gabriel Roldán-Roldán, Dinora Fabiola González Esquivel, Saé Muñiz-Hernández, Alelí Salazar, Maricela Méndez Armenta, Saúl Gómez-Manzo, Hugo González-Conchillos, Angélica Luna-Nophal, Alma Patrica Acosta Ramírez, Benjamín Pineda, Anabel Jiménez-Anguiano and Verónica Pérez de la Cruz

Cells 2022, 11(23), 3819; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11233819 - 29 Nov 2022

Viewed by 1924

Abstract

The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. Toxoplasma gondii is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels [...] Read more.

The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. Toxoplasma gondii is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels of IgG anti-T. gondii from mothers and their neonates, with a higher risk of developing schizophrenia. The absence of the parasite and the levels of IgGs found in the early stages of life suggest a transplacental transfer of the anti-T. gondii IgG antibodies, which could bind fetal brain structures by molecular mimicry and induce alterations in neurodevelopment. This study aimed to determine the maternal pathogenic antibodies formation that led to behavioral impairment on the progeny of rats immunized with T. gondii. Female rats were immunized prior to gestation with T. gondii lysate (3 times/once per week). The anti-T. gondii IgG levels were determined in the serum of pregestational exposed females’ previous mating. After this, locomotor activity, cognitive and social tests were performed. Cortical neurotransmitter levels for dopamine and glutamate were evaluated at 60 PND in the progeny of rats immunized before gestation (Pregestational group). The maternal pathogenic antibodies were evidenced by their binding to fetal brain mimotopes in the Pregestational group and the reactivity of the serum containing anti-T. gondii IgG was tested in control fetal brains (non-immunized). These results showed that the Pregestational group presented impairment in short and long-term memory, hypoactivity and alteration in social behavior, which was also associated with a decrease in cortical glutamate and dopamine levels. We also found the IgG antibodies bound to brain mimotopes in fetuses from females immunized with T. gondii, as well as observing a strong reactivity of the serum females immunized for fetal brain structures of fetuses from unimmunized mothers. Our results suggest that the exposure to T. gondii before gestation produced maternal pathogenic antibodies that can recognize fetal brain mimotopes and lead to neurochemical and behavioral alterations in the offspring. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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18 pages, 4732 KiB

Open AccessArticle

Rearing in an Enriched Environment Ameliorates the ADHD-like Behaviors of Lister Hooded Rats While Suppressing Neuronal Activities in the Medial Prefrontal Cortex

by Ryo Utsunomiya, Kanta Mikami, Tomomi Doi, Mohammed E. Choudhury, Toshihiro Jogamoto, Naohito Tokunaga, Eiichi Ishii, Mariko Eguchi, Hajime Yano and Junya Tanaka

Cells 2022, 11(22), 3649; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11223649 - 17 Nov 2022

Cited by 1 | Viewed by 1862

Abstract

In addition to genetic factors, environmental factors play a role in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). This study used Lister hooded rats (LHRs) as ADHD model animals to evaluate the effects of environmental factors. Male LHR pups were kept in four [...] Read more.

In addition to genetic factors, environmental factors play a role in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). This study used Lister hooded rats (LHRs) as ADHD model animals to evaluate the effects of environmental factors. Male LHR pups were kept in four rearing conditions from postnatal day 23 (4 rats in a standard cage; 12 rats in a large flat cage; and 4 or 12 rats in an enriched environment [EE]) until 9 weeks of age. EE rearing but not rearing in a large flat cage decreased the activity of LHRs in the open field test that was conducted for 7 consecutive days. In the drop test, most rats reared in an EE remained on a disk at a height, whereas most rats reared in a standard cage fell off. RNA sequencing revealed that the immediate-early gene expression in the medial prefrontal cortex of LHRs reared in an EE was reduced. cFos-expressing neurons were reduced in number in LHRs reared in an EE. These results suggest that growing in an EE improves ADHD-like behaviors and that said improvement is due to the suppression of neuronal activity in the mPFC. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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12 pages, 7032 KiB

Open AccessArticle

Febrile Seizures Cause Depression and Anxiogenic Behaviors in Rats

by Yeon Hee Yu, Seong-Wook Kim, Hyuna Im, Yejin Song, Seo Jeong Kim, Yu Ran Lee, Gun Woo Kim, Changmin Hwang, Dae-Kyoon Park and Duk-Soo Kim

Cells 2022, 11(20), 3228; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11203228 - 14 Oct 2022

Cited by 1 | Viewed by 1722

Abstract

Febrile seizure (FS) is a common type of seizure occurring in human during infancy and childhood. Although an epileptic seizure is associated with psychiatric disorders and comorbid diseases such as depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine, [...] Read more.

Febrile seizure (FS) is a common type of seizure occurring in human during infancy and childhood. Although an epileptic seizure is associated with psychiatric disorders and comorbid diseases such as depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine, the causal relationship between FS and psychiatric disorders is poorly understood. The objective of the current study was to investigate the relationship of FS occurrence in childhood with the pathogenesis of anxiety disorder and depression using an FS rat model. We induced febrile seizures in infantile rats (11 days postnatal) using a mercury vapor lamp. At 3 weeks and 12 weeks after FS induction, we examined behaviors and recorded local field potentials (LFPs) to assess anxiety and depression disorder. Interestingly, after FS induction in infantile rats, anxiogenic behaviors and depression-like phenotypes were found in both adult and juvenile FS rats. The analysis of LFPs revealed that 4–7 Hz hippocampal theta rhythm, a neural oscillatory marker for anxiety disorder, was significantly increased in FS rats compared with their wild-type littermates. Taken together, our findings suggest that FS occurrence in infants is causally related to increased levels of anxiety-related behaviors and depression-like symptoms in juvenile and adult rodents. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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22 pages, 2095 KiB

Open AccessArticle

Predation Stress Causes Excessive Aggression in Female Mice with Partial Genetic Inactivation of Tryptophan Hydroxylase-2: Evidence for Altered Myelination-Related Processes

by Evgeniy Svirin, Ekaterina Veniaminova, João Pedro Costa-Nunes, Anna Gorlova, Aleksei Umriukhin, Allan V. Kalueff, Andrey Proshin, Daniel C. Anthony, Andrey Nedorubov, Anna Chung Kwan Tse, Susanne Walitza, Lee Wei Lim, Klaus-Peter Lesch and Tatyana Strekalova

Cells 2022, 11(6), 1036; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11061036 - 18 Mar 2022

Cited by 4 | Viewed by 2827

Abstract

The interaction between brain serotonin (5-HT) deficiency and environmental adversity may predispose females to excessive aggression. Specifically, complete inactivation of the gene encoding tryptophan hydroxylase-2 (Tph2) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and [...] Read more.

The interaction between brain serotonin (5-HT) deficiency and environmental adversity may predispose females to excessive aggression. Specifically, complete inactivation of the gene encoding tryptophan hydroxylase-2 (Tph2) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (Tph2^−/−) mice. In heterozygous male mice (Tph2^+/−), there is a moderate reduction in brain 5-HT levels, and when they are exposed to stress, they exhibit increased aggression. Here, we exposed female Tph2^+/− mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. Tph2^+/− females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors Htr1a and Htr2a, glycogen synthase kinase-3 β (GSK-3β), and c-fos as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (Mbp), proteolipid protein 1 (Plp1), myelin-associated glycoprotein (Mag), and myelin oligodendrocyte glycoprotein (Mog). The expression of the plasticity markers synaptophysin (Syp) and cAMP response element binding protein (Creb), but not AMPA receptor subunit A2 (GluA2), were affected by genotype. Moreover, in a separate experiment, naïve female Tph2^+/− mice showed signs of enhanced stress resilience in the modified swim test with repeated swimming sessions. Taken together, the combination of a moderate reduction in brain 5-HT with environmental challenges results in behavioral changes in female mice that resemble the aggression-related behavior and resilience seen in stressed male mutants; additionally, the combination is comparable to the phenotype of null mutants lacking neuronal 5-HT. Changes in myelination-associated processes are suspected to underpin the molecular mechanisms leading to aggressive behavior. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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Review

Jump to: Research

17 pages, 1251 KiB

Open AccessReview

The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease

by Yanshree, Wing Shan Yu, Man Lung Fung, Chi Wai Lee, Lee Wei Lim and Kah Hui Wong

Cells 2022, 11(15), 2284; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11152284 - 24 Jul 2022

Cited by 11 | Viewed by 5384

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative [...] Read more.

Alzheimer’s disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD. A limited number of clinical studies have been conducted and several clinical trials are ongoing, which have thus far shown analogous outcomes to the preclinical studies. Nonetheless, future research on Hericium erinaceus needs to focus on elucidating the specific neuroprotective mechanisms and the target sites in AD. Additionally, standardized treatment parameters and universal regulatory systems need to be established to further ensure treatment safety and efficacy. In conclusion, Hericium erinaceus has therapeutic potential and may facilitate memory enhancement in patients with AD. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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19 pages, 644 KiB

Open AccessReview

Applying a Fast-Scan Cyclic Voltammetry to Explore Dopamine Dynamics in Animal Models of Neuropsychiatric Disorders

by Vladimir P. Grinevich, Amir N. Zakirov, Uliana V. Berseneva, Elena V. Gerasimova, Raul R. Gainetdinov and Evgeny A. Budygin

Cells 2022, 11(9), 1533; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11091533 - 03 May 2022

Cited by 9 | Viewed by 3292

Abstract

Progress in the development of technologies for the real-time monitoring of neurotransmitter dynamics has provided researchers with effective tools for the exploration of etiology and molecular mechanisms of neuropsychiatric disorders. One of these powerful tools is fast-scan cyclic voltammetry (FSCV), a technique which [...] Read more.

Progress in the development of technologies for the real-time monitoring of neurotransmitter dynamics has provided researchers with effective tools for the exploration of etiology and molecular mechanisms of neuropsychiatric disorders. One of these powerful tools is fast-scan cyclic voltammetry (FSCV), a technique which has progressively been used in animal models of diverse pathological conditions associated with alterations in dopamine transmission. Indeed, for several decades FSCV studies have provided substantial insights into our understanding of the role of abnormal dopaminergic transmission in pathogenetic mechanisms of drug and alcohol addiction, Parkinson’s disease, schizophrenia, etc. Here we review the applications of FSCV to research neuropsychiatric disorders with particular attention to recent technological advances. Full article

(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)

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