Environmental Effects on the Embryos and Fetuses of Experimental Animals

PEDIATRICS ◽  
1974 ◽  
Vol 53 (5) ◽  
pp. 821-822
Author(s):  
Robert L. Brent

In examining the offspring of experimental animals or man in relation to exposures to environmental agents, account should be taken of certain principles developed over the past five decades. TERATOGENESIS Before the Period of Implantation Experimental embryologic studies have shown that before implantation there is a so-called omnipotential period of development, when all cells have the ability to form a complete embryo. During this interval it is difficult, if not impossible, to induce congenital malformations. This interval extends to 6½ days in the mouse, 8 days in the rat, and about 12 to 13 days in man. Teratogenic Period The interval during which teratogenesis may be induced in man is short relative to the total gestational period, in contrast to the period of susceptibility in the mouse or rat, in which it is about one third of the gestational period. Fetal Period Subsequently, classical teratogens do not produce gross malformations that are easily observable at birth. Exposures to hazardous agents may still produce other effects throughout the later period of gestation, namely, cell deletions or tissue hypoplasia. This is a new area about which we do not yet understand very much, even with respect to high doses. When the mouse embryo is exposed late in gestation to 200 rad, a marked depletion has been observed in the cerebral cortex. This easily visible difference from normal upon inspection of the brain has little effect on behavior. In the same way, x-irradiation of the mouse testes produced hypoplasia, but no defect in morphogenesis.

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 884
Author(s):  
Natalia Yeste ◽  
Daniel Valent ◽  
Laura Arroyo ◽  
Marta Vázquez-Gómez ◽  
Consolación García-Contreras ◽  
...  

Supplementation of a mother’s diet with antioxidants, such as hydroxytyrosol (HTX), has been proposed to ameliorate the adverse phenotypes of fetuses at risk of intrauterine growth restriction. In the present study, sows were treated daily with or without 1.5 mg of HTX per kilogram of feed from day 35 of pregnancy (at 30% of total gestational period), and individuals were sampled at three different ages: 100-day-old fetuses and 1-month- and 6-month-old piglets. After euthanasia, the brain was removed and the hippocampus, amygdala, and prefrontal cortex were dissected. The profile of the catecholaminergic and serotoninergic neurotransmitters (NTs) was characterized and an immunohistochemical study of the hippocampus was performed. The results indicated that maternal supplementation with HTX during pregnancy affected the NT profile in a brain-area-dependant mode and it modified the process of neuron differentiation in the hippocampal CA1 and GD areas, indicating that cell differentiation occurred more rapidly in the HTX group. These effects were specific to the fetal period, concomitantly with HTX maternal supplementation, since no major differences remained between the control and treated groups in 1-month- and 6-month-old pigs.


1963 ◽  
Vol 205 (1) ◽  
pp. 177-180 ◽  
Author(s):  
Antonia Vernadakis ◽  
Paola S. Timiras

Electroshock seizure responses were studied in control and irradiated rats between 8 and 55 days of age. Experimental animals were exposed to 500 r whole-body X-irradiation 2 days postnatally. In maturing rats seizure patterns produced by brain stimulation with 50 ma current appear in sequence: hyperkinesia, clonus, forelimb flexion, forelimb extension followed by hind limb flexion, and hind limb flexion followed by hind limb extension. In irradiated rats full flexor-extensor seizure pattern appeared in 50% of animals at 13 days of age, 3 days earlier than in controls. Extension was longer and flexion, clonus, and total seizure were shorter in irradiated than in controls. In both groups durations of clonus and total seizure were related inversely to durations of extension. Duration of flexion decreased and duration of extension increased up to 22nd day of age in all animals. This indicates increased neuronal activity as the brain matures. Also thresholds for minimal electroshock convulsions decreased up to 22nd day of age, further indicating increased brain activity with maturation. Thresholds were significantly lower in irradiated rats than in controls.


Author(s):  
R.G. Frederickson ◽  
R.G. Ulrich ◽  
J.L. Culberson

Metallic cobalt acts as an epileptogenic agent when placed on the brain surface of some experimental animals. The mechanism by which this substance produces abnormal neuronal discharge is unknown. One potentially useful approach to this problem is to study the cellular and extracellular distribution of elemental cobalt in the meninges and adjacent cerebral cortex. Since it is possible to demonstrate the morphological localization and distribution of heavy metals, such as cobalt, by correlative x-ray analysis and electron microscopy (i.e., by AEM), we are using AEM to locate and identify elemental cobalt in phagocytic meningeal cells of young 80-day postnatal opossums following a subdural injection of cobalt particles.


Author(s):  
R. W. Cole ◽  
J. C. Kim

In recent years, non-human primates have become indispensable as experimental animals in many fields of biomedical research. Pharmaceutical and related industries alone use about 2000,000 primates a year. Respiratory mite infestations in lungs of old world monkeys are of particular concern because the resulting tissue damage can directly effect experimental results, especially in those studies involving the cardiopulmonary system. There has been increasing documentation of primate parasitology in the past twenty years.


2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.


Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.


2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.


2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.


Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1431
Author(s):  
Fadzai P. Mutingwende ◽  
Pierre P. D. Kondiah ◽  
Philemon Ubanako ◽  
Thashree Marimuthu ◽  
Yahya E. Choonara

Nanotechnology has aided in the advancement of drug delivery for the treatment of several neurological disorders including depression. Depression is a relatively common mental disorder which is characterized by a severe imbalance of neurotransmitters. Several current therapeutic regimens against depression display drawbacks which include low bioavailability, delayed therapeutic outcome, undesirable side effects and drug toxicity due to high doses. The blood–brain barrier limits the entry of the drugs into the brain matrix, resulting in low bioavailability and tissue damage due to drug accumulation. Due to their size and physico-chemical properties, nanotechnological drug delivery systems present a promising strategy to enhance the delivery of nanomedicines into the brain matrix, thereby improving bioavailability and limiting toxicity. Furthermore, ligand-complexed nanocarriers can improve drug specificity and antidepressant efficacy and reduce drug toxicity. Biopolymers and nanocarriers can also be employed to enhance controlled drug release and reduce the hepatic first-pass effect, hence reducing the dosing frequency. This manuscript reviews recent advances in different biopolymers, such as polysaccharides and other nanocarriers, for targeted antidepressant drug delivery to the brain. It probes nano-based strategies that can be employed to enhance the therapeutic efficacy of antidepressants through the oral, intranasal, and parenteral routes of administration.


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