title: Signaling pathways relevant to cognition-enhancing drug targets.
abstract: Aging is generally associated with a certain cognitive decline. However, individual differences exist. While age-related memory deficits can be observed in humans and rodents in the absence of pathological conditions, some individuals maintain intact cognitive functions up to an advanced age. The mechanisms underlying learning and memory processes involve the recruitment of multiple signaling pathways and gene expression, leading to adaptative neuronal plasticity and long-lasting changes in brain circuitry. This chapter summarizes the current understanding of how these signaling cascades could be modulated by cognition-enhancing agents favoring memory formation and successful aging. It focuses on data obtained in rodents, particularly in the rat as it is the most common animal model studied in this field. First, we will discuss the role of the excitatory neurotransmitter glutamate and its receptors, downstream signaling effectors [e.g., calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase C (PKC), extracellular signal-regulated kinases (ERK), mammalian target of rapamycin (mTOR), cAMP response element-binding protein (CREB)], associated immediate early gene (e.g., Homer 1a, Arc and Zif268), and growth factors [insulin-like growth factors (IGFs) and brain-derived neurotrophic factor (BDNF)] in synaptic plasticity and memory formation. Second, the impact of the cholinergic system and related modulators on memory will be briefly reviewed. Finally, since dynorphin neuropeptides have recently been associated with memory impairments in aging, it is proposed as an attractive target to develop novel cognition-enhancing agents.
authors.affiliation: Douglas Mental Health University Institute, McGill University, Perry Pavilion, 6875 LaSalle Boulevard, Montreal, QC, Canada, H4H 1R3.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ménard
authors.forename: Pierrette
authors.initials: P
authors.lastname: Gaudreau
authors.forename: Rémi
authors.initials: R
authors.lastname: Quirion
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004399:Dynorphins / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D009473:Neuronal Plasticity / Q000187:drug effects; D018697:Nootropic Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018697:Nootropic Agents; D004399:Dynorphins