Long-Term Functional and Cytoarchitectonic Effects of the Systemic Administration of the Histamine H1 Receptor Antagonist/Inverse Agonist Chlorpheniramine During Gestation in the Rat Offspring Primary Motor Cortex

Rocío Valle-Bautista, Berenice Márquez-Valadez, Gabriel Herrera-López, Ernesto Griego, Emilio J. Galván, Néstor Fabián Díaz, José Antonio Arias-Montaño, Anayansi Molina-Hernández*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The transient histaminergic system is among the first neurotransmitter systems to appear during brain development in the rat mesencephalon/rhombencephalon. Histamine increases FOXP2-positive deep-layer neuron differentiation of cortical neural stem cells through H1 receptor activation in vitro. The in utero or systemic administration of chlorpheniramine (H1 receptor antagonist/inverse agonist) during deep-layer cortical neurogenesis decreases FOXP2 neurons in the developing cortex, and H1R- or histidine decarboxylase-knockout mice show impairment in learning and memory, wakefulness and nociception, functions modulated by the cerebral cortex. Due to the role of H1R in cortical neural stem cell neurogenesis, the purpose of this study was to evaluate the postnatal impact of the systemic administration of chlorpheniramine during deep-layer cortical neuron differentiation (E12–14) in the primary motor cortex (M1) of neonates (P0) and 21-day-old pups (P21). Chlorpheniramine or vehicle were systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats at gestational days 12–14, and the expression and distribution of deep- (FOXP2 and TBR1) and superficial-layer (SATB2) neuronal cortical markers were analyzed in neonates from both groups. The qRT-PCR analysis revealed a reduction in the expression of Satb2 and FoxP2. However, Western blot and immunofluorescence showed increased protein levels in the chlorpheniramine-treated group. In P21 pups, the three markers showed impaired distribution and increased immunofluorescence in the experimental group. The Sholl analysis evidenced altered dendritic arborization of deep-layer neurons, with lower excitability in response to histamine, as evaluated by whole-cell patch-clamp recording, as well as diminished depolarization-evoked [3H]-glutamate release from striatal slices. Overall, these results suggest long-lasting effects of blocking H1Rs during early neurogenesis that may impact the pathways involved in voluntary motor activity and cognition.

Original languageEnglish (US)
Article number740282
JournalFrontiers in Neuroscience
Volume15
DOIs
StatePublished - Jan 24 2022

Bibliographical note

Funding Information:
We acknowledge funding by INPer and CONACyT to AM-H and CONACyT fellowship to RV-B (576845). We are grateful to Talía Estrada-Rojas (INPer) for assisting with animal care, and Raúl González-Pantoja (Cinvestav), Juan Escamilla-Sánchez (Cinvestav) and Graciela Santamaría-Méndez (Cinvestav) for assistance in binding and release assays.

Publisher Copyright:
Copyright © 2022 Valle-Bautista, Márquez-Valadez, Herrera-López, Griego, Galván, Díaz, Arias-Montaño and Molina-Hernández.

Keywords

  • cerebral cortex development
  • chlorpheniramine
  • cortical function
  • cytoarchitecture
  • hitamine H receptor
  • pregnancy

ASJC Scopus subject areas

  • General Neuroscience

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