Article

Cognitive decline is associated with reduced reelin expression in the entorhinal cortex of aged rats

Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
Cerebral Cortex (Impact Factor: 8.67). 02/2011; 21(2):392-400. DOI: 10.1093/cercor/bhq106
Source: PubMed

ABSTRACT Brain regions and neural circuits differ in their vulnerability to changes that occur during aging and in age-related neurodegenerative diseases. Among the areas that comprise the medial temporal lobe memory system, the layer II neurons of the entorhinal cortex, which form the perforant path input to the hippocampal formation, exhibit early alterations over the course of aging Reelin, a glycoprotein implicated in synaptic plasticity, is expressed by entorhinal cortical layer II neurons. Here, we report that an age-related reduction in reelin expression in the entorhinal cortex is associated with cognitive decline. Using immunohistochemistry and in situ hybridization, we observed decreases in the number of Reelin-immunoreactive cells and reelin messenger RNA expression in the lateral entorhinal cortex of aged rats that are cognitively impaired relative to young adults and aged rats with preserved cognitive abilities. The lateral entorhinal cortex of aged rats with cognitive impairment also exhibited changes in other molecular markers, including increased accumulation of phosphorylated tau and decreased synaptophysin immunoreactivity. Taken together, these findings suggest that reduced reelin expression, emanating from layer II entorhinal neurons, may contribute to network dysfunction that occurs during memory loss in aging.

0 Followers
 · 
110 Views
  • Source
    • "In the context of aging, altered transcriptional regulation of genes that promote or are necessary for synaptic plasticity is associated with memory impairment in aged rodents (Blalock et al. 2003; Rowe et al. 2007; Haberman et al. 2011). Affected genes implicated in plasticity notably include the immediate-early genes HomerI1a, and Arc (activity regulated cytoskeleton-associated protein ), which are necessary for learning and memory (Penner et al. 2011), as well as zif268, bdnf (brain-derived neurotrophic factor ) (Hattiangady et al. 2005), and reelin (Stranahan et al. 2011). Data derived from a rodent model of neurocognitive aging in which old Long-Evans rats show individual variability in cognitive outcome highlight the marked changes in hippocampal gene transcription that occur in association with age-related memory impairment, thereby distinguishing neurobiological signatures that are specifically associated with age-related memory decline from changes coupled with chronological age, unrelated to cognitive outcome. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic modifications of chromatin structure provide a mechanistic interface for gene-environment interactions that impact the individualization of health trajectories across the lifespan. A growing body of research indicates that dysfunctional epigenetic regulation contributes to poor cognitive outcomes among aged populations. Here we review neuroepigenetic research as it relates to cognitive aging, focusing specifically on memory function mediated by the hippocampal system. Recent work that differentiates epigenetic contributions to chronological aging from influences on mindspan, or the preservation of normal cognitive abilities across the lifespan, is also highlighted. Together, current evidence indicates that while age-related memory impairment is associated with dysfunction in the coordinated regulation of chromatin modification, animal models that show individual differences in cognitive outcome underscore the enormous mechanistic complexity that surrounds epigenetic dynamics in the aged hippocampus.
    Learning & memory (Cold Spring Harbor, N.Y.) 10/2014; 21(10):569-574. DOI:10.1101/lm.033506.113 · 4.38 Impact Factor
  • Source
    • "The LEC appeared to be affected in aging more than the MEC, because there was reduced synaptophysin, decreased reelin and increased phosphorylated tau in LEC neurons in layer II of aged animals, when the MEC did not appear to be altered (Stranahan et al., 2010). Notably, some animals lacked abnormalities; when animals were tested using the Morris water maze, those rats with impairments had layer II defects, but the others that performed normally had no detectable changes in the EC (Stranahan et al., 2010). Although correlative, the results suggested that neurons in layer II, especially in LEC, could play an important role in age-related cognitive impairment. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A major problem in the field of neurodegeneration is the basis of selective vulnerability of subsets of neurons to disease. In aging, Alzheimer's disease (AD), and other disorders such as temporal lobe epilepsy, the superficial layers of the entorhinal cortex (EC) are an area of selective vulnerability. In AD, it has been suggested that the degeneration of these neurons may play a role in causing the disease because it occurs at an early stage. Therefore, it is important to define the distinctive characteristics of the EC that make this region particularly vulnerable. It has been shown that neurotrophins such as brain-derived neurotrophic factor (BDNF) are critical to the maintenance of the cortical neurons in the adult brain, and specifically the EC. Here we review the circuitry, distinctive functions, and neurotrophin-dependence of the EC that are relevant to its vulnerability. We also suggest that a protein that is critical to the actions of BDNF, the ARMS/Kidins220 scaffold protein, plays an important role in neurotrophic support of the EC.
    Cognitive neuroscience 08/2013; 4(3-4). DOI:10.1080/17588928.2013.826184 · 2.38 Impact Factor
  • Source
    • "Rats were behaviorally categorized based on their performance in the hippocampus-dependent version of the water maze, as described (Stranahan et al., 2011). Aged rats that performed within the range of young, as measured by using an index score derived from proximity to the goal platform location during interpolated probe trials, were classified as aged-unimpaired (AU), whereas rats that performed outside of the range of young were designated aged-impaired (AI). "
    [Show abstract] [Hide abstract]
    ABSTRACT: For many years, aging was thought to be accompanied by significant decreases in total neuron number across multiple brain regions. However, this view was revised with the advent of modern quantification methods, and it is now widely accepted that the hippocampus and many regions of the cortex show substantially preserved numbers of neurons during normal aging. Nonetheless, age-related changes in neuron number do occur in focal regions of the primate prefrontal cortex (PFC), but the question of whether age-related neuron loss is an exclusive characteristic of the PFC in primates remains relatively unexplored. To investigate the loss of neurons with normal aging in rodents, we used unbiased stereological methods to quantify the number of principal neurons and interneurons in the PFC of young and aged rats. We observed a significant age-related decline in the number of principal neurons in the dorsal PFC. The number of interneurons positively stained with antibodies to glutamic acid decarboxylase 67 was also reduced in the dorsal PFC of aged rats. These observations indicate that the dorsal PFC is susceptible to neuron loss with aging in rodent brain and suggest some common basis for vulnerability in cortical circuits across species.
    The Journal of Comparative Neurology 04/2012; 520(6):1318-26. DOI:10.1002/cne.22790 · 3.51 Impact Factor
Show more

Preview

Download
2 Downloads
Available from