Cells (Jan 2022)

Age-Dependent and Pathway-Specific Bimodal Action of Nicotine on Synaptic Plasticity in the Hippocampus of Mice Lacking the miR-132/212 Genes

  • Tamara Stojanovic,
  • David Velarde Gamez,
  • Gabor Jorrid Schuld,
  • Daniel Bormann,
  • Maureen Cabatic,
  • Pavel Uhrin,
  • Gert Lubec,
  • Francisco J. Monje

DOI
https://doi.org/10.3390/cells11020261
Journal volume & issue
Vol. 11, no. 2
p. 261

Abstract

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Nicotine addiction develops predominantly during human adolescence through smoking. Self-administration experiments in rodents verify this biological preponderance to adolescence, suggesting evolutionary-conserved and age-defined mechanisms which influence the susceptibility to nicotine addiction. The hippocampus, a brain region linked to drug-related memory storage, undergoes major morpho-functional restructuring during adolescence and is strongly affected by nicotine stimulation. However, the signaling mechanisms shaping the effects of nicotine in young vs. adult brains remain unclear. MicroRNAs (miRNAs) emerged recently as modulators of brain neuroplasticity, learning and memory, and addiction. Nevertheless, the age-dependent interplay between miRNAs regulation and hippocampal nicotinergic signaling remains poorly explored. We here combined biophysical and pharmacological methods to examine the impact of miRNA-132/212 gene-deletion (miRNA-132/212−/−) and nicotine stimulation on synaptic functions in adolescent and mature adult mice at two hippocampal synaptic circuits: the medial perforant pathway (MPP) to dentate yrus (DG) synapses (MPP-DG) and CA3 Schaffer collaterals to CA1 synapses (CA3–CA1). Basal synaptic transmission and short-term (paired-pulse-induced) synaptic plasticity was unaltered in adolescent and adult miRNA-132/212−/− mice hippocampi, compared with wild-type controls. However, nicotine stimulation promoted CA3–CA1 synaptic potentiation in mature adult (not adolescent) wild-type and suppressed MPP-DG synaptic potentiation in miRNA-132/212−/− mice. Altered levels of CREB, Phospho-CREB, and acetylcholinesterase (AChE) expression were further detected in adult miRNA-132/212−/− mice hippocampi. These observations propose miRNAs as age-sensitive bimodal regulators of hippocampal nicotinergic signaling and, given the relevance of the hippocampus for drug-related memory storage, encourage further research on the influence of miRNAs 132 and 212 in nicotine addiction in the young and the adult brain.

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