engleski

In utero exposure to antihistamines affects rat brain expression of H1R and Np65

Aim. To investigate the effects of in utero exposure to the antihistamines bilastine or desloratadine on the expression level of the brain histamine receptor 1 (H1R), and neuroplastin receptor 65 (Np65) (marker of synaptogenesis). Material and methods. The following animal groups were studied: the offspring of untreated mothers as controls (C), and the offspring of mothers treated with bilastine (B) or desloratadine (D). Mother were treated from gestation day 10 until delivery. Each group comprised 6 male (m) and 6 female (f) Sprague-Dawley rats. When the offspring reached age 3 months, brain tissue was collected and immunostained for H1R and Np65. The H1R and Np65 expression levels were analyzed within hippocampal DG and CA3 regions, and the tuberomammillary nucleus (TMN). Results. Bilastin treatment had opposite effects on hippocampal H1R expression in males and females: B(m) vs. C(m) had significantly more H1R in DG (p=0.028) and CA3 (p>0.001), but B(f) vs. C(f) had significantly less in CA3 (p=0.037). The relay nucleus – TMN was affected negatively in the B(m) (p=0.033) and positively in the D(f) (p=0.024) animal groups. Females had more Np65 than males within all analyzed brain regions. The effects of sex and in utero exposure to antihistamines contributed to a significantly lower Np65 expression level in CA3 in the B(m) and D(m) groups (C(m) vs. B(m) p=0.002, C(m) vs. D(m) p<0.001). Discussion and conclusions. In utero exposure to bilastine in males contributed to the increase of H1R and decrease of Np65 expression levels within the hippocampus and TMN which could interfere with normal behavior concerning motivation, focus, memory, and exploration. These results are in accordance with our previous findings concerning reduced cortical thickness (especially layer IV involved in processing sensory input), increased neuron to glia ratio within the primary auditory region of the cerebral cortex, and lower spontaneous and locomotor activities of males that were exposed to bilastine during early development. Funding: The study has been funded by Bohdan Malaniak CSMC - RECOOP Young Scientists Research Award #014 BMYSRG 2019-2020 Sztojkov-Ivanov – Gaspar. Ethical Committee Approval: Hungarian Ethical Committee for Animal Research, registration number IV/3796/2015, issue date: September 18, 2015. Acknowledgement: This study was supported by Cedars- Sinai Medical Center’s International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) and the participating Cedars-Sinai Medical Center - RECOOP Research Centers (CRRCs).

Histamine antagonists, Sprague-Dawley rats, brain, histamine receptor 1, neuroplastin receptor 65

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