Systemic injection of an H4 receptor agonist induces a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex in mice

Abstract

Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal ( ip ) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

Intracerebellar Microinjection of an H4 Agonist Impairs Memory Consolidation in Open Field and Rotarod Tasks in Mice

“…In our laboratory, we demonstrated that VUF 8430 impaired emotional memory consolidation in mice via the cerebellar vermis, regardless of whether the proposed activities were related to anxiety, as in the elevated plus maze, or related to fear, as in an inhibitory avoidance task [15]. Furthermore, a decrease in protein expression in the cerebellar vermis was verified by CREB and phosphorylated CREB levels, which corroborates these deficits [16].…”

Central Histaminergic Signaling, Neural Excitability and Epilepsy

“…Activation of H4R leads to inhibition of CREB in the cerebellar vermis and prefrontal cortex (Fernandes & Serafim, 2019). Also, H4R targets and inactivates the downstream extracellular signal-regulated kinase (ERK)-CREB pathway (Sanna, Mello, Masini & Galeotti, 2018).…”

“…H4R antagonists inhibit vestibular neuron activity (Desmadryl et al, 2012), suggests H4R involves in vestibular neuron excitability. Agonists or antagonists target H4R are commonly used to assess the function of H4R in some behavioral and disease phenotypes (Fernandes & Serafim, 2019;Fernandes, Serafim, Gianlorenco & Mattioli, 2017;Sanna, Borgonetti, Masini & Galeotti, 2020;Zhou et al, 2019). Recently years, H4R KO mice were also applied to investigate the behavioral phenotype and its neural function (Sanna, Ghelardini, Thurmond, Masini & Galeotti, 2017).…”