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Animal Research Model for Neurological Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 16898

Special Issue Editors


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Guest Editor
Department of Veterinary Sciences, University of Messina, Via Palatucci s.n., Annunziata Universitary Pole, 98168 Messina, Italy
Interests: morphometry; veterinary anatomy; zebrafish; imaging; experimental model; natural compounds; obesity; immunohistochemistry; molecular biology; sensory system; regeneration of sensory cells
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Guest Editor
Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany
Interests: gene regulation; transcription; neurogenesis; zebrafish; regeneration; neural stem cell
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Animal modeling of human disease has a fundamental role in scientific studies aimed at explaining disease mechanisms and conducting pre-clinical studies on potential therapies. The careful selection of experimental models for complex pathologies, such as neurological diseases, becomes crucial for ensuring high-quality research outcomes. Consequently, the progress made in animal modeling and the introduction of new models in recent years have significantly contributed to our improved understanding of the principal disease mechanisms of the central nervous system. Numerous aquatic or terrestrial vertebrates, including wild type, transgenic, and mutant models, have been introduced over the past few decades. While the mouse model remains pivotal in central nervous system pathology research, other models such as the zebrafish have also demonstrated remarkable success. This Special Issue aims to explore the morpho-physiopathology and molecular pathways involved in neurological disorders, utilizing both established canonical models and emerging animal models. We invite submissions of full research articles and comprehensive review papers for this Special Issue. This Special Issue is assisted by our Topical Advisory Panel Member Dr. Kamel Mhalhel.

Dr. Giuseppe Montalbano
Dr. Sepand Rastegar
Guest Editors

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Keywords

  • experimental models
  • mouse
  • rat
  • zebrafish
  • neurological Disease
  • Alzheimer’s disease
  • Parkinson’s disease
  • neurodegeneration
  • neuroregeneration

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Published Papers (11 papers)

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Research

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18 pages, 1710 KiB  
Article
Mouse Model of Parkinson’s Disease with Bilateral Dorsal Striatum Lesion with 6-Hydroxydopamine Exhibits Cognitive Apathy-like Behavior
by Masato Okitsu, Masayo Fujita, Yuki Moriya, Hiroko Kotajima-Murakami, Soichiro Ide, Rika Kojima, Kazunari Sekiyama, Kazushi Takahashi and Kazutaka Ikeda
Int. J. Mol. Sci. 2024, 25(14), 7993; https://doi.org/10.3390/ijms25147993 - 22 Jul 2024
Viewed by 1111
Abstract
Among the symptoms of Parkinson’s disease (PD), apathy comprises a set of behavioral, affective, and cognitive features that can be classified into several subtypes. However, the pathophysiology and brain regions that are involved in these different apathy subtypes are still poorly characterized. We [...] Read more.
Among the symptoms of Parkinson’s disease (PD), apathy comprises a set of behavioral, affective, and cognitive features that can be classified into several subtypes. However, the pathophysiology and brain regions that are involved in these different apathy subtypes are still poorly characterized. We examined which subtype of apathy is elicited in a mouse model of PD with 6-hydroxydopamine (6-OHDA) lesions and the behavioral symptoms that are exhibited. Male C57/BL6J mice were allocated to sham (n = 8) and 6-OHDA (n = 13) groups and locally injected with saline or 4 µg 6-OHDA bilaterally in the dorsal striatum. We then conducted motor performance tests and apathy-related behavioral experiments. We then pathologically evaluated tyrosine hydroxylase (TH) immunostaining. The 6-OHDA group exhibited significant impairments in motor function. In the behavioral tests of apathy, significant differences were observed between the sham and 6-OHDA groups in the hole-board test and novelty-suppressed feeding test. The 6-OHDA group exhibited impairments in inanimate novel object preference, whereas social preference was maintained in the three-chamber test. The number of TH+ pixels in the caudate putamen and substantia nigra compacta was significantly reduced in the 6-OHDA group. The present mouse model of PD predominantly showed dorsal striatum dopaminergic neuronal loss and a decrease in novelty seeking as a symptom that is related to the cognitive apathy component. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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17 pages, 2676 KiB  
Article
Comparative Brain Proteomic Analysis between Sham and Cerebral Ischemia Experimental Groups
by María Candamo-Lourido, Antonio Dopico-López, Esteban López-Arias, Sonia López-Amoedo, Clara Correa-Paz, María Pilar Chantada-Vázquez, Ana Bugallo-Casal, Lucía del Pozo-Filíu, Lara Pérez-Gayol, Nuria Palomar-Alonso, Susana B. Bravo, Francisco Campos and María Pérez-Mato
Int. J. Mol. Sci. 2024, 25(14), 7538; https://doi.org/10.3390/ijms25147538 - 9 Jul 2024
Viewed by 1060
Abstract
Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one of the most common models of middle cerebral artery occlusion (MCAO) used in the study of brain ischemia. However, a sham [...] Read more.
Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one of the most common models of middle cerebral artery occlusion (MCAO) used in the study of brain ischemia. However, a sham group is usually not included in the experimental design of these studies. In this study, we aimed to evaluate the relevance of the sham group by analyzing and comparing the brain protein profiles of the sham and MCAO groups. In the sham group, 98 dysregulated proteins were detected, compared to 171 in the ischemic group. Moreover, a comparative study of protein profiles revealed the existence of a pool of 57 proteins that appeared to be dysregulated in both sham and ischemic animals. These results indicated that the surgical procedure required for the intraluminal occlusion of the middle cerebral artery (MCA) induces changes in brain protein expression that are not associated with ischemic lesions. This study highlights the importance of including sham control groups in the experimental design, to ensure that surgical intervention does not affect the therapeutic target under study. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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18 pages, 8370 KiB  
Article
Urtica dioica Extract Abrogates Chlorpyrifos-Induced Toxicity in Zebrafish Larvae
by Kamel Mhalhel, Yassine Kadmi, Ahlem Ben Chira, Maria Levanti, Lidia Pansera, Marzio Cometa, Mirea Sicari, Antonino Germanà, Marialuisa Aragona and Giuseppe Montalbano
Int. J. Mol. Sci. 2024, 25(12), 6631; https://doi.org/10.3390/ijms25126631 - 16 Jun 2024
Viewed by 1484
Abstract
Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects on human health. In this regard, Urtica dioica stands out as a promising candidate for counteracting chemical ‘contaminant’ toxicity thanks to its [...] Read more.
Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects on human health. In this regard, Urtica dioica stands out as a promising candidate for counteracting chemical ‘contaminant’ toxicity thanks to its therapeutic properties. Therefore, our study aimed to investigate the potential of an Urtica dioica ethanolic extract (UDE) to mitigate chlorpyrifos-induced toxicity. Eight compounds in the Urtica dioica ethanolic extract have been identified, most of which present significant potential as antioxidant, anti-inflammatory, and neuroprotective agents. Chlorpyrifos exposure altered hatching rates, increased the incidence of teratogenic effects, and upregulated the expression of brain-derived neurotrophic factor (Bdnf) in zebrafish larvae telencephalon. On the other hand, UDE demonstrated a preventive effect against CPF-induced teratogenicity, which is expressed by a lower morphological deformity rate. Moreover, the UDE showed a rather protective effect, maintaining the physiological condition of the telencephalon. Additionally, CPF altered the locomotor behavior of larvae, which was characterized by irregular swimming and increased activity. This defective behavioral pattern was slightly attenuated by the UDE. Our findings suggest that the UDE possesses significant protective properties against CPF-induced toxicity, probably conferred by its natural antioxidant and anti-inflammatory contents. Still, further research is needed to elucidate the recruited mechanisms and implicated pathways on UDE’s protective effects. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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14 pages, 1889 KiB  
Article
PolyI:C Maternal Immune Activation on E9.5 Causes the Deregulation of Microglia and the Complement System in Mice, Leading to Decreased Synaptic Spine Density
by Shuxin Yan, Le Wang, James Nicholas Samsom, Daniel Ujic and Fang Liu
Int. J. Mol. Sci. 2024, 25(10), 5480; https://doi.org/10.3390/ijms25105480 - 17 May 2024
Cited by 1 | Viewed by 1470
Abstract
Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA [...] Read more.
Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA protocol throughout development to understand how prenatal immune insult alters the trajectory of important neurodevelopmental processes, including the microglial regulation of synaptic spines and complement signaling. We used polyinosinic:polycytidylic acid (polyI:C) to induce MIA on gestational day 9.5 in CD-1 mice, and measured their synaptic spine density, microglial synaptic pruning, and complement protein expression. We found reduced dendritic spine density in the somatosensory cortex starting at 3-weeks-of-age with requisite increases in microglial synaptic pruning and phagocytosis, suggesting spine density loss was caused by increased microglial synaptic pruning. Additionally, we showed dysregulation in complement protein expression persisting into adulthood. Our findings highlight disruptions in the prenatal environment leading to alterations in multiple dynamic processes through to postnatal development. This could potentially suggest developmental time points during which synaptic processes could be measured as risk factors or targeted with therapeutics for neurodevelopmental disorders. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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9 pages, 1240 KiB  
Communication
Lactate Dehydrogenase-Elevating Virus Infection Inhibits MOG Peptide Presentation by CD11b+CD11c+ Dendritic Cells in a Mouse Model of Multiple Sclerosis
by Pyone Pyone Soe, Mélanie Gaignage, Mohamed F. Mandour, Etienne Marbaix, Jacques Van Snick and Jean-Paul Coutelier
Int. J. Mol. Sci. 2024, 25(9), 4950; https://doi.org/10.3390/ijms25094950 - 1 May 2024
Viewed by 1254
Abstract
Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized [...] Read more.
Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized with the myelin oligodendrocyte glycoprotein peptide (MOG35–55) experienced paralysis and lost weight at a greater rate than mice who had previously been infected with LDV. LDV infection decreased the presentation of the MOG peptide by CD11b+CD11c+ dendritic cells (DC) to pathogenic T lymphocytes. When comparing non-infected mice to infected mice, the histopathological examination of the CNS showed more areas of demyelination and CD45+ and CD3+, but not Iba1+ cell infiltration. These results suggest that the protective effect of LDV infection against EAE development is mediated by a suppression of myelin antigen presentation by a specific DC subset to autoreactive T lymphocytes. Such a mechanism might contribute to the general suppressive effect of infections on autoimmune diseases known as the hygiene hypothesis. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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29 pages, 3860 KiB  
Article
Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos
by Daniela Zizioli, Eugenia Quiros-Roldan, Sara Ferretti, Luca Mignani, Giorgio Tiecco, Eugenio Monti, Francesco Castelli and Isabella Zanella
Int. J. Mol. Sci. 2024, 25(9), 4640; https://doi.org/10.3390/ijms25094640 - 24 Apr 2024
Viewed by 1460
Abstract
Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may [...] Read more.
Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior–posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain–hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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11 pages, 1449 KiB  
Article
Rats Selected for Different Nervous Excitability: Long-Term Emotional–Painful Stress Affects the Dynamics of DNA Damage in Cells of Several Brain Areas
by Veronika Shcherbinina, Marina Pavlova, Eugene Daev and Natalia Dyuzhikova
Int. J. Mol. Sci. 2024, 25(2), 994; https://doi.org/10.3390/ijms25020994 - 13 Jan 2024
Cited by 1 | Viewed by 1213
Abstract
The maintenance of genome stability is critical for health, but during individual ontogenesis, different stressors affect DNA integrity, which can lead to functional and/or structural changes in the cells of target organs. In the nervous system, cell genome destabilization is associated with different [...] Read more.
The maintenance of genome stability is critical for health, but during individual ontogenesis, different stressors affect DNA integrity, which can lead to functional and/or structural changes in the cells of target organs. In the nervous system, cell genome destabilization is associated with different neurological and psychiatric diseases, but experiments in vivo, where a link between stress and DNA instability has been demonstrated, are relatively rare. Here, we use rat strains selected for the contrast excitability of the tibialis nerve (n. tibialis) and nonselected Wistar rats to investigate the reasons for individual differences in developing post-stress pathologies. Previous research on the behavioral response of these strains to prolonged emotional–painful stress (PEPS) allows us to consider one strain as a model of post-traumatic stress disorder (PTSD) and another strain as a model of compulsive disorder (CD). We study DNA damage in the cells of the prefrontal cortex (PFC), hippocampus, and amygdala, regions involved in stress responses and the formation of post-stress dysfunctions. The evaluation of cell genome integrity via the comet assay shows different responses to PEPS in each brain area analyzed and for all strains used. This could help us to understand the reasons for individual differences in the consequences of stress and the pathophysiology of post-stress disease formation. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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15 pages, 6882 KiB  
Article
Swine Pudendal Nerve as a Model for Neuromodulation Studies to Restore Lower Urinary Tract Dysfunction
by Alice Giannotti, Stefania Musco, Vincenzo Miragliotta, Giulia Lazzarini, Andrea Pirone, Angela Briganti, Claudio Verardo, Fabio Bernini, Giulio Del Popolo and Silvestro Micera
Int. J. Mol. Sci. 2024, 25(2), 855; https://doi.org/10.3390/ijms25020855 - 10 Jan 2024
Viewed by 1528
Abstract
Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having [...] Read more.
Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the real-time need of the bladder. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimizing the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morphophysiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the fasciculate nature of the nerve and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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18 pages, 1384 KiB  
Article
An Adapted GeneSwitch Toolkit for Comparable Cellular and Animal Models: A Proof of Concept in Modeling Charcot-Marie-Tooth Neuropathy
by Laura Morant, Maria-Luise Petrovic-Erfurth and Albena Jordanova
Int. J. Mol. Sci. 2023, 24(22), 16138; https://doi.org/10.3390/ijms242216138 - 9 Nov 2023
Viewed by 1442
Abstract
Investigating the impact of disease-causing mutations, their affected pathways, and/or potential therapeutic strategies using disease modeling often requires the generation of different in vivo and in cellulo models. To date, several approaches have been established to induce transgene expression in a controlled manner [...] Read more.
Investigating the impact of disease-causing mutations, their affected pathways, and/or potential therapeutic strategies using disease modeling often requires the generation of different in vivo and in cellulo models. To date, several approaches have been established to induce transgene expression in a controlled manner in different model systems. Several rounds of subcloning are, however, required, depending on the model organism used, thus bringing labor-intensive experiments into the technical approach and analysis comparison. The GeneSwitch™ technology is an adapted version of the classical UAS-GAL4 inducible system, allowing the spatial and temporal modulation of transgene expression. It consists of three components: a plasmid encoding for the chimeric regulatory pSwitch protein, Mifepristone as an inducer, and an inducible plasmid. While the pSwitch-containing first plasmid can be used both in vivo and in cellulo, the inducible second plasmid can only be used in cellulo. This requires a specific subcloning strategy of the inducible plasmid tailored to the model organism used. To avoid this step and unify gene expression in the transgenic models generated, we replaced the backbone vector with standard pUAS-attB plasmid for both plasmids containing either the chimeric GeneSwitch™ cDNA sequence or the transgene cDNA sequence. We optimized this adapted system to regulate transgene expression in several mammalian cell lines. Moreover, we took advantage of this new system to generate unified cellular and fruit fly models for YARS1-induced Charco–Marie–Tooth neuropathy (CMT). These new models displayed the expected CMT-like phenotypes. In the N2a neuroblastoma cells expressing YARS1 transgenes, we observed the typical “teardrop” distribution of the synthetase that was perturbed when expressing the YARS1CMT mutation. In flies, the ubiquitous expression of YARS1CMT induced dose-dependent developmental lethality and pan-neuronal expression caused locomotor deficit, while expression of the wild-type allele was harmless. Our proof-of-concept disease modeling studies support the efficacy of the adapted transgenesis system as a powerful tool allowing the design of studies with optimal data comparability. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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Review

Jump to: Research

30 pages, 1226 KiB  
Review
Animal Models of Autistic-like Behavior in Rodents: A Scoping Review and Call for a Comprehensive Scoring System
by Asher Ornoy, Boniface Echefu and Maria Becker
Int. J. Mol. Sci. 2024, 25(19), 10469; https://doi.org/10.3390/ijms251910469 - 28 Sep 2024
Viewed by 1864
Abstract
Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as autism spectrum disorder (ASD) necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior [...] Read more.
Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as autism spectrum disorder (ASD) necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. If possible, the severity of the symptoms should also be assessed. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, communication deficits, and restricted, repetitive behavioral patterns, with association to several additional impairments such as somatosensory, motor, and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD-like-behavior from the etiologic, pathogenetic, and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), lipopolysaccharide (LPS), and propionic acid, or other well-documented immunogens or pathogens, like Mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, polychlorinated biphenyls (PCBs), organophosphate pesticides like chlorpyrifos (CPF), and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic-like behavior (i.e., fragile X, Rett syndrome, SHANK gene mutation, neuroligin genes, and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior, but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans. We therefore propose a scoring system for improved assessment of ASD-like behavior in animal models. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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40 pages, 3784 KiB  
Review
Neurological Disorders Induced by Drug Use: Effects of Adolescent and Embryonic Drug Exposure on Behavioral Neurodevelopment
by Olga Karatayev, Adam D. Collier, Stella R. Targoff and Sarah F. Leibowitz
Int. J. Mol. Sci. 2024, 25(15), 8341; https://doi.org/10.3390/ijms25158341 - 30 Jul 2024
Viewed by 1806
Abstract
Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, [...] Read more.
Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, are observed not only in adults but also with drug use during adolescence and after prenatal exposure to these drugs, and they are accompanied by long-lasting disturbances in brain development. This report provides overviews of clinical and preclinical studies, which confirm these adverse effects in adolescents and the offspring prenatally exposed to the drugs and include a more in-depth description of specific neuronal systems, their neurocircuitry and molecular mechanisms, affected by drug exposure and of specific techniques used to determine if these effects in the brain are causally related to the behavioral disturbances. With analysis of further studies, this review then addresses four specific questions that are important for fully understanding the impact that drug use in young individuals can have on future pregnancies and their offspring. Evidence demonstrates that the adverse effects on their brain and behavior can occur: (1) at low doses with short periods of drug exposure during pregnancy; (2) after pre-conception drug use by both females and males; (3) in subsequent generations following the initial drug exposure; and (4) in a sex-dependent manner, with drug use producing a greater risk in females than males of developing SUDs with emotional conditions and female offspring after prenatal drug exposure responding more adversely than male offspring. With the recent rise in drug use by adolescents and pregnant women that has occurred in association with the legalization of cannabis and increased availability of vaping tools, these conclusions from the clinical and preclinical literature are particularly alarming and underscore the urgent need to educate young women and men about the possible harmful effects of early drug use and to seek novel therapeutic strategies that might help to limit drug use in young individuals. Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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