Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein immunoreactivity in corticocortically projecting neurons in macaque and patas monkeys

Hof, Patrick R.; Duan, Huiling; Page, Tanya L.; Einstein, Michael; Wicinski, Bridget; He, Yong; Erwin, J.; Morrison, John H.

doi:10.1016/s0006-8993(01)03345-5

Cited by 79 publications

(56 citation statements)

References 62 publications

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“…Together with alterations in neuronal gene expression (Colombo et al, 1997;Guarente and Kenyon, 2000;Murphy et al, 2003), intracellular transport, neurotransmitter systems-receptors (Arnsten et al, 1995;Gazzaley et al, 1997;Hof et al, 2002), synapses (Tigges et al, 1995;Smith et al, 2000), dendrites-spines (Uemura, 1985a,b;Peters et al, 1994;Hayashi et al, 2001;, electrophysiological mechanisms (Tanila et al, 1997), astroglial (Sloane et al, 2000), and white matter changes (Peters, 2002), a more comprehensive picture of mechanisms underlying age-related neural degeneration emerges. The mechanism of this degeneration is likely multifactorial and varies, depending on the brain region affected.…”

Section: Discussionmentioning

confidence: 99%

Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons

Smith¹,

Rapp²,

McKay³

et al. 2004

J. Neurosci.

123

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Mechanisms of cognitive decline with aging remain primarily unknown. We determined whether localized cell loss occurred in brain regions associated with age-related cognitive decline in primates. On a task requiring the prefrontal cortex, aged monkeys were impaired in maintaining representations in working memory. Stereological quantification in area 8A, a prefrontal region associated with working memory, demonstrated a significant 32 Ϯ 11% reduction in the number of Nissl-stained neurons compared with young monkeys. Furthermore, the number of immunolabeled cholinergic neurons projecting to this region of cortex from the nucleus basalis was also reduced by 50 Ϯ 6%. In contrast, neuronal number was strikingly preserved in an adjoining prefrontal cortical region also associated with working memory, area 46, and in the component of the nucleus basalis projecting to this region. These findings demonstrate extensive but highly localized loss of neocortical neurons in aged, cognitively impaired monkeys that likely contributes to cognitive decline. Cell degeneration, when present, extends transneuronally.

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Section: Discussionmentioning

confidence: 99%

Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons

Smith¹,

Rapp²,

McKay³

et al. 2004

J. Neurosci.

123

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“…Additionally, synaptic aging was associated with decline in mitochondrial activity, reduced antioxidant contents, increased oxidative stress markers and increased sensitivity to Aβ toxicity in resting and depolarized synaptic terminals [161]. Structural changes in neurons and dendritic spines, as well as alterations in neurotransmitter receptors and in electrophysiological properties, were found in normal aging [162,163]. It is interesting also to relate the changes observed along normal aging, MCI and AD.…”

Section: Neuronal Impairment In Agingmentioning

confidence: 99%

Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer’s Disease

2015

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline that afflicts as many as 45 % of individuals who survive past the age of 85. AD has been associated with neurovascular dysfunction and brain accumulation of amyloid-β peptide, as well as tau phosphorylation and neurodegeneration, but the pathogenesis of the disease is still somewhat unclear. According to the amyloid cascade hypothesis of AD, accumulation of amyloid-β peptide (Aβ) aggregates initiates a sequence of events leading to neuronal injury and loss, and dementia. Alternatively, the vascular hypothesis of AD incorporates the vascular contribution to the disease, stating that a primary insult to brain microcirculation (e.g., stroke) not only contributes to amyloidopathy but initiates a non-amyloidogenic pathway of vascular-mediated neuronal dysfunction and injury, which involves blood-brain barrier compromise, with increased permeability of blood vessels, leakage of blood-borne components into the brain, and, consequently, neurotoxicity. Vascular dysfunction also includes a diminished brain capillary flow, causing multiple focal ischemic or hypoxic microinjuries, diminished amyloid-β clearance, and formation of neurotoxic oligomers, which lead to neuronal dysfunction. Here we present and discuss relevant findings on the contribution of vascular alterations during aging to AD, with the hope that a better understanding of the players in the "orchestra" of neurodegeneration will be useful in developing therapies to modulate the "symphony".

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“…Aging results in a significant reduction of GluR2 and NR1 expression on neurons that project to area 46 (from the superior temporal sulcus, area 7a, and the contralateral area 46) in monkeys (Hof et al 2002).…”

Section: Glutamatementioning

confidence: 99%

“…Additionally, GluR2 expression on corticocortical neurons within area 46 is also decreased with age in monkeys (Hof et al 2002). Despite these age-related changes in glutamate receptor subunits, none of them have been studied in behaviorally characterized monkeys, which will be fruitful avenues of research.…”

Section: Glutamatementioning

confidence: 99%

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Hara

Rapp

Morrison

2011

AGE

Self Cite

120

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Rhesus monkeys provide a valuable model for studying the basis of cognitive aging because they are vulnerable to age-related decline in executive function and memory in a manner similar to humans. Some of the behavioral tasks sensitive to the effects of aging are the delayed response working memory test, recognition memory tests including the delayed nonmatching-to-sample and the delayed recognition span task, and tests of executive function including reversal learning and conceptual set-shifting task. Much effort has been directed toward discovering the neurobiological parameters that are coupled to individual differences in age-related cognitive decline. Area 46 of the dorsolateral prefrontal cortex (dlPFC) has been extensively studied for its critical role in executive function while the hippocampus and related cortical regions have been a major target of research for memory function. Some of the key age-related changes in area 46 include decreases in volume, microcolumn strength, synapse density, and α1-and α2-adrenergic receptor binding densities. All of these measures significantly correlate with cognitive scores. Interestingly, the critical synaptic subtypes associated with cognitive function appear to be different between the dlPFC and the hippocampus. For example, the dendritic spine subtype most critical to task acquisition and vulnerable to aging in area 46 is the thin spine, whereas in the dentate gyrus, the density of AGE (2012) large mushroom spines with perforated synapses correlates with memory performance. This review summarizes age-related changes in anatomical, neuronal, and synaptic parameters within brain areas implicated in cognition and whether these changes are associated with cognitive decline.

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Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein immunoreactivity in corticocortically projecting neurons in macaque and patas monkeys

Cited by 79 publications

References 62 publications

Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons

Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons

Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer’s Disease

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

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