Gastrin-releasing peptide receptor signaling in the integration of stress and memory

A Stress-Related Peptide Bombesin Centrally Induces Frequent Urination through Brain Bombesin Receptor Types 1 and 2 in the Rat

“…A third mammalian bombesin receptor (type 3) is also reported, but its native ligands are unknown to date (see the review by Jensen et al, 2008). Bombesin-like peptides have a wide range of central functions, including learning and memory (Shumyatsky et al, 2002;Presti-Torres et al, 2007;Roesler et al, 2012), thermoregulation (Tsushima et al, 2003), regulation of anxiety and fear response (Merali et al, 2006(Merali et al, , 2013Bédard et al, 2007), and regulation of food intake (Ladenheim and Knipp, 2007), in addition to regulation of stress responses (Merali et al, 2002;Roesler et al, 2014). For instance, in rodent models, exposure to acute stress, such as a restraint and an aversive stimulus, increases immunoreactivity and in vivo release of bombesinlike peptides in the brain Merali et al, 1998Merali et al, , 2008, and BB receptor antagonists show anxiolytic effects in the elevated plus maze test and attenuating effects on fearpotentiated startle responses (Merali et al, 2006;Bédard et al, 2007).…”

Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction

“…The findings show that HDACis protect against memory loss caused by GRPR inhibition. HDACis have shown promise as cognitive enhancers in several experimental models of memory dysfunction associated with aging and brain disorders [1,12,18,26], and GRPR dysfunction may contribute to cognitive impairment in neurodevelopmental disease [43,45,52]. From a translational perspective, characterization of the relationship between GRPR signaling and histone acetylation may thus help revealing novel approaches to treating neurodegenerative and psychiatric disorders.…”

“…Upon activation, GRPRs enhance memory formation through stimulation of multiple protein kinase intracellular signaling pathways [45,46,49,52]. Dorsal hippocampal microinfusions of the GRPR agonist recombinant bombesin enhance the consolidation of memory for inhibitory avoidance (IA); this effect is prevented by inhibitors of protein kinase C (PKC), extracellular signal-regulated protein kinase (ERK)/mitogen-activated protein kinase (MAPK), cAMP/protein kinase A (PKA), and phosphoinositide 3-kinase (PI3K) signaling pathways [45,49,53]. Conversely, systemic, intrahippocampal, or intraamygdala administration of the synthetic GRPR peptidergic antagonist, RC-3095, impairs IA memory [47,48,50].…”

“…In addition, pharmacological inhibition of the GRPR early in life produces long lasting behavioral alterations, including memory deficits [43]. Indeed, we have proposed that GRPR signaling dysfunction contributes to the cognitive impairment associated with neurodevelopmental and neurodegenerative disorders [35,45,52].…”

Administration of a Histone Deacetylase Inhibitor into the Basolateral Amygdala Enhances Memory Consolidation, Delays Extinction, and Increases Hippocampal BDNF Levels

“…These processes are mediated and regulated by a range of neurotransmitter and neuropeptide receptors, intracellular protein kinase signaling pathways, and transcription factors, resulting in changes in gene transcription. Brain areas critically involved in mediating or regulating the formation and extinction of IA memory include the dorsal hippocampus and the basolateral amygdala (BLA; McGaugh, 2000; Roesler and McGaugh, 2010; Roesler and Schröder, 2011; Roozendaal and McGaugh, 2011; Alberini and Kandel, 2014; Furini et al, 2014; Roesler et al, 2014a; Izquierdo et al, 2016). The BLA is proposed to interact with the hippocampus and related structures to enhance the consolidation of memory for events that trigger fear or aversiveness (McGaugh, 2002; McIntyre et al, 2003).…”