WITHDRAWN: Long-term Learning Deficits Following Developmental Exposure to the Flame Retardant decaBDE

Abstract We previously showed that developmental 3,4-methylenedioxymethamphetamine (MDMA) treatment induces long-term spatial and egocentric learning and memory deficits and serotonin (5-HT) reductions. During brain development, 5-HT is a neurotrophic factor influencing neurogenesis, synaptogenesis, migration, and target field organization. MDMA (10 mg/kg × 4/d at 2 h intervals) given on post-natal day (PD) 11–20 in rats (a period of limbic system development that approximates human third trimester brain development) induces 50% reductions in 5-HT during treatment and 20% reductions when assessed as adults. To determine whether the 5-HT reduction is responsible for the cognitive deficits, we used citalopram (Cit) pretreatment to inhibit the effects of MDMA on 5-HT reuptake in a companion study. Cit attenuated MDMA-induced 5-HT reductions by 50% (Schaefer et al., 2012). Here we tested whether Cit (5 or 7.5 mg/kg × 2/d) pretreatment attenuates the cognitive effects of MDMA. Within each litter, different offspring were treated on PD11–20 with saline (Sal) + MDMA, Cit + MDMA, Cit + Sal or Sal + Sal. Neither spatial nor egocentric learning/memory was improved by Cit pretreatment. Unexpectedly, Cit + Sal (at both doses) produced spatial and egocentric learning deficits as severe as those caused by Sal + MDMA. These are the first data showing cognitive deficits resulting from developmental exposure to a selective serotonin reuptake inhibitor. These data indicate the need for further research on the long-term safety of antidepressants during pregnancy.

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Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer’s Disease Brain Extract in Mouse Brains

Journal of Alzheimer s Disease ◽

10.3233/jad-201002 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1701-1711

Author(s):

Tetsuo Hayashi ◽

Shotaro Shimonaka ◽

Montasir Elahi ◽

Shin-Ei Matsumoto ◽

Koichi Ishiguro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Brain ◽

Functional Decline ◽

Brain Regions ◽

Insoluble Fraction ◽

Brain Extract ◽

Post Injection ◽

Learning Deficits

Background: Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective: To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods: We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results: After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion: These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

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Pre- and Post-Natal Stress Programming: Developmental Exposure to Glucocorticoids Causes Long-Term Brain-Region Specific Changes to Transcriptome in the Precocial Japanese Quail

Journal of Neuroendocrinology ◽

10.1111/jne.12387 ◽

2016 ◽

Vol 28 (5) ◽

Cited By ~ 19

Author(s):

V. Marasco ◽

P. Herzyk ◽

J. Robinson ◽

K. A. Spencer

Keyword(s):

Japanese Quail ◽

Brain Region ◽

Developmental Exposure

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Developmental exposure to silver nanoparticles leads to long term gut dysbiosis and neurobehavioral alterations

Scientific Reports ◽

10.1038/s41598-021-85919-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhen Lyu ◽

Shreya Ghoshdastidar ◽

Karamkolly R. Rekha ◽

Dhananjay Suresh ◽

Jiude Mao ◽

...

Keyword(s):

Silver Nanoparticles ◽

Body Fat ◽

Repetitive Behaviors ◽

Developmental Exposure ◽

Male And Female ◽

Female Mice ◽

Gut Dysbiosis ◽

Study Results ◽

Wide Range

AbstractDue to their antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of consumer products that includes topical wound dressings, coatings for biomedical devices, and food-packaging to extend the shelf-life. Despite their beneficial antimicrobial effects, developmental exposure to such AgNPs may lead to gut dysbiosis and long-term health consequences in exposed offspring. AgNPs can cross the placenta and blood–brain-barrier to translocate in the brain of offspring. The underlying hypothesis tested in the current study was that developmental exposure of male and female mice to AgNPs disrupts the microbiome–gut–brain axis. To examine for such effects, C57BL6 female mice were exposed orally to AgNPs at a dose of 3 mg/kg BW or vehicle control 2 weeks prior to breeding and throughout gestation. Male and female offspring were tested in various mazes that measure different behavioral domains, and the gut microbial profiles were surveyed from 30 through 120 days of age. Our study results suggest that developmental exposure results in increased likelihood of engaging in repetitive behaviors and reductions in resident microglial cells. Echo-MRI results indicate increased body fat in offspring exposed to AgNPs exhibit. Coprobacillus spp., Mucispirillum spp., and Bifidobacterium spp. were reduced, while Prevotella spp., Bacillus spp., Planococcaceae, Staphylococcus spp., Enterococcus spp., and Ruminococcus spp. were increased in those developmentally exposed to NPs. These bacterial changes were linked to behavioral and metabolic alterations. In conclusion, developmental exposure of AgNPs results in long term gut dysbiosis, body fat increase and neurobehavioral alterations in offspring.

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