Experience on the Barnes Spatial Maze Influences PKCγ Levels in the Hippocampus

Nithianantharajah, Jess; Murphy, Mark

doi:10.1080/00207450802328508

Cited by 11 publications

(12 citation statements)

References 36 publications

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“…Protein kinase C gamma (PKCγ) is specific to neurons and colocalized with mGluR5 [42]. It has also been previously associated with learning and memory processes [43], [44], [45], [46]. PKCγ total protein level was similar in all groups (Fig.…”

Section: Resultsmentioning

confidence: 74%

Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways

2012

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Normal aging is associated with impairments in cognition, especially learning and memory. However, major individual differences are known to exist. Using the classical Morris Water Maze (MWM) task, we discriminated a population of 24-months old Long Evans aged rats in two groups - memory-impaired (AI) and memory-unimpaired (AU) in comparison with 6-months old adult animals. AI rats presented deficits in learning, reverse memory and retention. At the molecular level, an increase in metabotropic glutamate receptors 5 (mGluR5) was observed in post-synaptic densities (PSD) in the hippocampus of AU rats after training. Scaffolding Homer 1b/c proteins binding to group 1 mGluR facilitate coupling with its signaling effectors while Homer 1a reduces it. Both Homer 1a and 1b/c levels were up-regulated in the hippocampus PSD of AU animals following MWM task. Using immunohistochemistry we further demonstrated that mGluR5 as well as Homer 1b/c stainings were enhanced in the CA1 hippocampus sub-field of AU animals. In fact mGluR5 and Homer 1 isoforms were more abundant and co-localized in the hippocampal dendrites in AU rats. However, the ratio of Homer 1a/Homer 1b/c bound to mGluR5 in the PSD was four times lower for AU animals compared to AI rats. Consequently, AU animals presented higher PKCγ, ERK, p70S6K, mTOR and CREB activation. Finally the expression of immediate early gene Arc/Arg3.1 was shown to be higher in AU rats in accordance with its role in spatial memory consolidation. On the basis of these results, a model of successful cognitive aging with a critical role for mGluR5, Homer 1 proteins and downstream signalling pathways is proposed here.

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Section: Resultsmentioning

confidence: 74%

Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways

2012

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“…In addition to this role in synaptic plasticity, PKC is known to be essential for learning and memory. Training in a spatial memory task has been shown to increase expression of PKC gamma [114]. Furthermore, PKC activity is reduced in aged rats compared to middle-aged and young counterparts [115].…”

Section: Changes In the Aging Hippocampusmentioning

confidence: 99%

Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease

Hullinger

Puglielli

2017

Behavioural Brain Research

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As the population of people aged 60 or older continues to rise, it has become increasingly important to understand the molecular basis underlying age-related cognitive decline. In fact, a better understanding of aging biology will help us identify ways to maintain high levels of cognitive functioning throughout the aging process. Many cellular and molecular aspects of brain aging are shared with other organ systems; however, certain age-related changes are unique to the nervous system due to its structural, cellular and molecular complexity. Importantly, the brain appears to show differential changes throughout the aging process, with certain regions (e.g. frontal and temporal regions) being more vulnerable than others (e.g. brain stem). Within the medial temporal lobe, the hippocampus is especially susceptible to age-related changes. The important role of the hippocampus in age-related cognitive decline and in vulnerability to disease processes such as Alzheimer’s disease has prompted this review, which will focus on the complexity of changes that characterize aging, and on the molecular connections that exist between normal aging and Alzheimer’s disease. Finally, it will discuss behavioral interventions and emerging insights for promoting healthy cognitive aging.

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“…Moreover, mGluR activity can enhance NMDAR currents via a PKC-dependent mechanism (Tyszkiewicz et al 2004). For example, following training in a spatial memory task PKC gamma (γ) expression increases (Nithianantharajah and Murphy 2009). This kinase was linked to the individual differences observed in the cognitive status of aging rats (Coalombo et al 1997;Colombo and Gallagher 2002;Menard and Quirion 2012b), and its activation in small groups of hippocampal or cortical neurons improves old rat performances in the MWM task (Zhang et al 2009).…”

Section: Pkcmentioning

confidence: 95%

“…These serine-threonine kinases are central to many signal transduction pathways and densely expressed in the brain (Saito et al 1988). PKC isoforms seem to play an essential role in multiple forms of learning and memory processes (Bank et al 1988;Olds et al 1989;Coalombo et al 1997;Colombo and Gallagher 2002;Nelson et al 2008;Nithianantharajah and Murphy 2009;Zhang et al 2009;Menard and Quirion 2012b). Inhibition of kinases such as PKC can block LTP induction (Malinow et al 1989).…”

Section: Pkcmentioning

confidence: 97%

Signaling Pathways Relevant to Cognition-Enhancing Drug Targets

Ménard

Gaudreau

Quirion

2015

Handbook of Experimental Pharmacology

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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.

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Experience on the Barnes Spatial Maze Influences PKCγ Levels in the Hippocampus

Cited by 11 publications

References 36 publications

Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways

Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways

Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease

Signaling Pathways Relevant to Cognition-Enhancing Drug Targets

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