BTVT ameliorates offspring blood<b>-</b>brain barrier damage induced by prenatal and lactational neodymium oxide exposure via the gut<b>-</b>brain axis.

Xiaoyan DU; Xiaocheng GAO; Jing CAO; Xin ZHAO; Zhi HUO; Shaoqing ZHAO; Qingqing LIANG; Lei GAO; Yang DENG

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BTVT ameliorates offspring blood-brain barrier damage induced by prenatal and lactational neodymium oxide exposure via the gut-brain axis.

Author: Xiaoyan DU ^{1
,

2
,

3} ; Xiaocheng GAO ⁴ ; Jing CAO ¹ ; Xin ZHAO ¹ ; Zhi HUO ¹ ; Shaoqing ZHAO ¹ ; Qingqing LIANG ⁵ ; Lei GAO ⁶ ; Yang DENG ^{3
,

4
,

7}
Author Information

1. School of Public Health, Baotou Medical College, Baotou
2. dxy60691811@
3. com.
4. Department of Social Medicine, Baotou Medical College, Baotou
5. Department of Hygiene Inspection and Hygiene Chemistry, Baotou Medical College, Baotou
6. Department of Pediatrics, Adolescent Health and Maternal and Child Health Care, Baotou Medical College, Baotou 014040, China.
7. yangdeng20150007@
Publication Type:Journal Article
Keywords: bifidobacterium tetrad viable tablet; blood-brain barrier; gut microbiota; neodymium oxide; rare earth elements
MeSH: Animals; Female; Blood-Brain Barrier/pathology*; Pregnancy; Rats, Sprague-Dawley; Rats; Male; Neodymium/toxicity*; Prenatal Exposure Delayed Effects/prevention & control*; Lactation; Maternal Exposure/adverse effects*; Brain
From: Journal of Central South University(Medical Sciences) 2025;50(4):615-624
CountryChina
Language:English
Abstract: OBJECTIVES:Exposure to rare earth elements (REEs) has been linked to various systemic diseases, but their impact on the offspring blood-brain barrier (BBB) via the gut-brain axis remains unclear. This study aims to investigate the effects of maternal exposure to neodymium oxide (Nd₂O₃) on the BBB integrity of offspring rats, and to evaluate the potential protective role of bifidobacterium tetrad viable tablets (BTVT) against Nd₂O₃-induced intestinal and BBB damage.
METHODS:Healthy adult SD rats were mated at a 1:1 male-to-female ratio, with the day of vaginal plug detection marked as gestational day 0. A total of 60 pregnant rats were randomly assigned to the following groups: Control, 50 mg/(kg·d) Nd₂O₃, 100 mg/(kg·d) Nd₂O₃, 200 mg/(kg·d) Nd₂O₃, and 200 mg/(kg·d) Nd₂O₃ + BTVT group. Treatments were administered by daily oral gavage throughout pregnancy and lactation. On postnatal day 21 (weaning), offspring feces, brain, and colon tissues were collected. Hematoxylin and eosin (HE) staining was used to assess structural changes in brain and intestinal tissues. Short-chain fatty acids (SCFAs) in feces were quantified by gas chromatography-mass spectrometry (GC-MS). Evans Blue (EB) dye extravasation assessed BBB permeability. Gene and protein expression levels of tight junction proteins occludin and zonula occludens-1 (ZO-1) were measured by reverse transcription PCR (RT-PCR) and Western blotting (WB), respectively. Neodymium levels in brain tissue were determined via inductively coupled plasma mass spectrometry (ICP-MS).
RESULTS:HE staining revealed that maternal Nd₂O₃ exposure caused mucosal edema, increased submucosal spacing, and lymphocyte infiltration in offspring colon, as well as neuronal degeneration and vacuolization in brain tissue. BTVT intervention alleviated these changes. GC-MS analysis showed that levels of acetic acid, propionic acid, butyric acid, and isobutyric acid significantly decreased, while valeric acid and isovaleric acid increased in offspring of Nd₂O₃-exposed mothers (P<0.05). BTVT significantly restored levels of acetic, propionic, and isobutyric acids and reduced valeric acid content (P<0.05). EB permeability was significantly elevated in Nd₂O₃-exposed offspring brains (P<0.05), but reduced with BTVT treatment (P<0.05). RT-PCR and WB showed downregulation of occludin and ZO-1 expression following Nd₂O₃ exposure (P<0.05), which was reversed by BTVT (P<0.05). ICP-MS results indicated significantly increased brain neodymium levels in offspring from all Nd₂O₃-exposed groups (P<0.05), while BTVT significantly reduced neodymium accumulation compared to the 200 mg/(kg·d) Nd₂O₃ group (P<0.05).
CONCLUSIONS:Maternal exposure to Nd₂O₃ during pregnancy and lactation disrupts intestinal health and BBB integrity in offspring, elevates brain neodymium accumulation, and induces neuronal degeneration. BTVT effectively mitigates Nd₂O₃-induced intestinal and BBB damage in offspring, potentially through modulation of the gut-brain axis.