scholarly journals Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marya Kayyal ◽  
Tanvi Javkar ◽  
M. Firoz Mian ◽  
Dana Binyamin ◽  
Omry Koren ◽  
...  
Keyword(s):  
Early Life ◽  
Low Dose ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Male Mice ◽  
Long Term Effects ◽  
Probiotic Treatment ◽  
Relevant Dose ◽  
Brain Behavior

Abstract There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received L. rhamnosus JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.

scholarly journals Early-Life Exposure to Low-Dose Cadmium Accelerates Diethylnitrosamine and Diet-Induced Liver Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hongbo Men ◽  
Jamie L. Young ◽  
Wenqian Zhou ◽  
Haina Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Early Life ◽  
Low Dose ◽  
Liver Tumors ◽  
Cadmium Exposure ◽  
Male Mice ◽  
Nonalcoholic Fatty Liver ◽  
Early Life Exposure ◽  
The Impact

Maternal exposure to cadmium causes obesity and metabolic changes in the offspring, including nonalcoholic fatty liver disease-like pathology. However, whether maternal cadmium exposure accelerates liver cancer in the offspring is unknown. This study investigated the impact of early-life exposure to cadmium on the incidence and potential mechanisms of hepatocellular carcinoma (HCC) in offspring subjected to postweaning HCC induction. HCC in C57BL/6J mice was induced by diethylnitrosamine (DEN) injection at weaning, followed by a long-term high-fat choline-deficient (HFCD) diet. Before weaning, liver cadmium levels were significantly higher in mice with early-life cadmium exposure than in those without cadmium exposure. However, by 26 and 29 weeks of age, hepatic cadmium fell to control levels, while a significant decrease was observed in copper and iron in the liver. Both male and female cadmium-exposed mice showed increased body weight compared to non-cadmium-treated mice. For females, early-life cadmium exposure also worsened insulin intolerance but did not significantly promote DEN/HFCD diet-induced liver tumors. In contrast, in male mice, early-life cadmium exposure enhanced liver cancer induction by DEN/HFCD with high incidence and larger liver tumors. The liver peritumor tissue of early-life cadmium-exposed mice exhibited greater inflammation and disruption of fatty acid metabolism, accompanied by higher malondialdehyde and lower esterified triglyceride levels compared to mice without cadmium exposure. These findings suggest that early-life exposure to low-dose cadmium accelerates liver cancer development induced by a DEN/HFCD in male mice, probably due to chronic lipotoxicity and inflammation caused by increased uptake but decreased consumption of fatty acids.

scholarly journals From Short- to Long-Term Effects of C-Section Delivery on Microbiome Establishment and Host Health

2021 ◽  
Vol 9 (10) ◽  
pp. 2122
Author(s):  
David Ríos-Covian ◽  
Philippe Langella ◽  
Rebeca Martín
Keyword(s):  
Gut Microbiota ◽  
Early Life ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
The Body ◽  
Vaginal Microbiome ◽  
Long Term Effects ◽  
Host Health ◽  
Gut Microbiota Composition

The establishment of gut microbiota has been proven to be impacted by several factors during pregnancy, delivery, and neonate periods. The body of evidence describing C-section delivery (CSD) as one of the most disruptive events during early life has expanded in recent years, concluding that CSD results in a drastic change in microbiota establishment patterns. When comparing the gut microbiota composition of CSD babies with vaginally delivered (VD) babies, the former show a microbiome that closely resembles that found in the environment and the mother’s skin, while VD babies show a microbiome more similar to the vaginal microbiome. Although these alterations of normal gut microbiota establishment tend to disappear during the first months of life, they still affect host health in the mid–long term since CSD has been correlated with a higher risk of early life infections and non-transmissible diseases, such as inflammatory diseases, allergies, and metabolic diseases. In recent years, this phenomenon has also been studied in other mammals, shedding light on the mechanisms involved in the effects of a CSD on host health. In addition, strategies to revert the disruptions in gut microbiomes caused by a CSD are currently in the process of development and evaluation. In this review, we discuss the recent advances in CSD research, from the alteration of gut microbiota establishment to the possible effects on host health during early life and development.

scholarly journals Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease

2019 ◽  
Vol 12 (4) ◽  
pp. 969-979 ◽  
Author(s):  
Carrie-Anne Malinczak ◽  
Wendy Fonseca ◽  
Andrew J. Rasky ◽  
Catherine Ptaschinski ◽  
Susan Morris ◽  
...  
Keyword(s):  
Early Life ◽  
Innate Immune ◽  
Male Mice ◽  
Long Term Effects ◽  
Interferon Β ◽  
Viral Control ◽  
Female Mice ◽  
Immune Alterations ◽  
Rsv Infection

AbstractMany studies have linked severe RSV infection during early-life with an enhanced likelihood of developing childhood asthma, showing a greater susceptibility in boys. Our studies show that early-life RSV infection leads to differential long-term effects based upon the sex of the neonate; leaving male mice prone to exacerbation upon secondary allergen exposure while overall protecting female mice. During initial viral infection, we observed better viral control in the female mice with correlative expression of interferon-β that was not observed in male mice. Additionally, we observed persistent immune alterations in male mice at 4 weeks post infection. These alterations include Th2 and Th17-skewing, innate cytokine expression (Tslp and Il33), and infiltration of innate immune cells (DC and ILC2). Upon exposure to allergen, beginning at 4 weeks following early-life RSV-infection, male mice show severe allergic exacerbation while female mice appear to be protected. Due to persistent expression of TSLP following early-life RSV infection in male mice, genetically modified TSLPR−/− mice were evaluated and demonstrated an abrogation of allergen exacerbation in male mice. These data indicate that TSLP is involved in the altered immune environment following neonatal RSV-infection that leads to more severe responses in males during allergy exposure, later in life. Thus, TSLP may be a clinically relevant therapeutic target early in life.

Ovarian Dysfunction in Fetally Irradiated Beagles

1977 ◽  
Vol 35 ◽  
pp. 658-659
Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Low Dose ◽  
Long Term Effects ◽  
Ovarian Dysfunction ◽  
Dose Rates ◽  
Highly Sensitive ◽  
Microscopic Evaluation ◽  
Ovarian Pathology ◽  
Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

The Neurobiology of Pain

2019 ◽  
pp. 387-414
Author(s):  
Maria Fitzgerald ◽  
Michael W. Salter
Keyword(s):  
Early Life ◽  
Pain Perception ◽  
Long Term Effects ◽  
Male And Female ◽  
Functional Changes ◽  
Pain Pathways ◽  
Developmental Age ◽  
Short And Long Term ◽  
Age And Sex

The influence of development and sex on pain perception has long been recognized but only recently has it become clear that this is due to specific differences in underlying pain neurobiology. This chapter summarizes the evidence for mechanistic differences in male and female pain biology and for functional changes in pain pathways through infancy, adolescence, and adulthood. It describes how both developmental age and sex determine peripheral nociception, spinal and brainstem processing, brain networks, and neuroimmune pathways in pain. Finally, the chapter discusses emerging evidence for interactions between sex and development and the importance of sex in the short- and long-term effects of early life pain.

Long term effects of early life stress on HPA circuit in rodent models

2021 ◽  
Vol 521 ◽  
pp. 111125
Author(s):  
Lucy Babicola ◽  
Rossella Ventura ◽  
Sebastian Luca D'Addario ◽  
Donald Ielpo ◽  
Diego Andolina ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Rodent Models ◽  
Long Term Effects

Long-term effects of early life stress on the brain monoamines level in the rats

2013 ◽  
Vol 43 (1) ◽  
pp. 79
Author(s):  
R. Ghalamghash ◽  
H.Z. Mammedov ◽  
H. Ashayeri ◽  
A. Hosseini
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Long Term Effects ◽  
Brain Monoamines ◽  
The Brain

Long-term effects of early pain and injury

2021 ◽  
pp. 21-37
Author(s):  
Orla Moriarty ◽  
Suellen M. Walker
Keyword(s):  
Nervous System ◽  
Early Life ◽  
Tissue Injury ◽  
Afferent Input ◽  
Laboratory Studies ◽  
Long Term Effects ◽  
Nociceptive Pathways ◽  
Noxious Stimuli ◽  
Underlying Mechanisms

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.

scholarly journals First Insights into the Effect of Low-Dose X-Ray Irradiation in Adipose-Derived Stem Cells

2019 ◽  
Vol 20 (23) ◽  
pp. 6075 ◽  
Author(s):  
Annemarie Schröder ◽  
Stephan Kriesen ◽  
Guido Hildebrandt ◽  
Katrin Manda
Keyword(s):  
Stem Cells ◽  
Low Dose ◽  
Dose Range ◽  
Adipose Derived Stem Cells ◽  
Long Term Effects ◽  
Low Dose Radiation ◽  
Term Survival ◽  
Cell Therapies ◽  
Dose Radiation

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.

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