The aging hippocampus: A multi-level analysis in the rat

Driscoll, Ira; Howard, Sarah R.; Stone, Jared C.; Monfils, Marie‐H.; Tomanek, Bogusław; Brooks, William M.; Sutherland, Robert J.

doi:10.1016/j.neuroscience.2006.01.040

Cited by 198 publications

(149 citation statements)

References 202 publications

(338 reference statements)

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“…DCX immunoreactive cells were found to decrease with age in both groups. This result concurs with previous studies which found that neurogenesis dramatically declined in the dentate gyrus during aging [5,7,11,12,17,23,25,28]. In addition, Kronenberg et al [16] compared young adult SHR and stroke-prone SHR (SHRSP) with the genetic control WKY strain: in both SHR and SHRSP, newly generated DCX immunoreactive neurons were significantly high compared to WKY strain.…”

Section: Discussionsupporting

confidence: 90%

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Hwang

Yoon

Choi

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. Spontaneously hypertensive rats (SHRs) are widely accepted in medical research because this model has been used for studies in neurodegenerative diseases such as vascular dementia and stroke. In the present study, we observed newly generated neuronal precursors using doublecortin (DCX, a marker of neural proliferation and differentiation) in the subgranular zone of the dentate gyrus in SHRs compared to Sprague-Dawley rats (SDRs) at various age stages. DCX immunoreactivity, immunoreactive cell numbers and its protein level in the dentate gyrus of the SHRs were higher than those in the SDRs at postnatal month 1 (PM 1). At PM 8, DCX immunoreactivity, immunoreactive cell numbers and protein levels in both groups were markedly decreased compared to those at PM 1; however, they were higher than those in the SDRs. They were decreased in the both groups with age: DCX immunoreactive cells in the SDRs were few at PM 12. Our results indicate that newly generated neuronal precursors are more abundant in SHRs than in SDRs during their life. KEY WORDS: development, doublecortin, neurogenesis, spontaneously hypertensive rat.J. Vet. Med. Sci. 70(4): 373-377, 2008 Spontaneously hypertensive rats (SHRs) are normotensive at birth and gradually develop stable hypertension during the first months of life. These rats are used as a genetic model of hypertension, which is widely accepted in medical research because it has features in common with idiopathic hypertension in man [20,21]. Moreover, this animal model has been used recently in studies of neurodegenerative diseases, such as, vascular dementia and stroke, because hypertension is a primary risk factor of these conditions [9,10].It has been reported that the rate of granule cell generation in the dentate gyrus of the adult mouse is dependent on strain [14,15]. In addition, significantly more newly generated cells and greater proliferation were found in the dentate gyrus of the young SHRs than in the young Sprague-Dawley rats (SDRs) [22]. However, they examined newly generated cells in the dentate gyrus using the thymidine analog bromodeoxyuridine (BrdU), which is labeled on newly generated glial cells as well as neuronal precursors [18].DCX gene encodes a 40-kDa microtubule-associated protein, which is specifically expressed in neuronal precursors in the developing and adult CNS. It is known that during CNS development DCX expression is associated with the migration and differentiation of neuronal precursors [3,4,13], and as a result, DCX is frequently used as a marker of newly generated neurons, not glial cells. In the present study, we investigated differences in distribution of DCX immunoreactive neuronal precursors in the dentate gyrus of SHRs and SDRs at various age stages. MATERIALS AND METHODSExperimental animals: Male SHRs and SDRs were obtained from the Experimental Animal Center, Hallym University, Chuncheon, South Korea. Postnatal month 1 (PM 1) (n=12), PM 8 (n=12) and PM 12 (n=12) rats in each strain were housed in a conventional state under adequate tem...

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Section: Discussionsupporting

confidence: 90%

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Hwang

Yoon

Choi

et al. 2008

The Journal of Veterinary Medical Science

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“…A common characteristic of advancing age is a gradual decline in cognitive functions associated with the progressive reduction of structural and functional plasticity in brain regions such as cerebral cortex and hippocampus that play a key role in cognition (Benice et al 2006;Driscoll et al 2006;Hara et al 2012; Van der Jeugd et al 2013). Studies in rats and non-human primates have demonstrated that aging impairs the functional integrity of prefrontal cortex neurons (Morrison and Baxter 2012) which is associated with decline in structural plasticity and cognitive performance (Dumitriu et al 2010;Bloss et al 2011Bloss et al , 2013.…”

Section: Introductionmentioning

confidence: 99%

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

Kumar

Thakur

2015

AGE

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Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed. In the present study, we have examined the age-related changes in the expression of these proteins in cerebral cortex and hippocampus of 10-, 30-, 50-, and 80-week-old male mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis indicated that messenger RNA (mRNA) level of Nrxn1 and Nlgn3 significantly increased from 10 to 30 weeks and then decreased at 50 weeks in both the regions. However, in 80-week-old mice, Nrxn1 and Nlgn3 were further downregulated in cerebral cortex while Nrxn1 was downregulated and Nlgn3 was upregulated in hippocampus. These findings were corroborated by immunoblotting and immunofluorescence results. When the expression of Nrxn1 and Nlgn3 was correlated with presynaptic density marker synaptophysin, it was found that synaptophysin protein expression in cerebral cortex was high at 10 weeks and decreased gradually up to 80 weeks, whereas in hippocampus, it decreased until 50 weeks and then increased remarkably at 80 weeks. Furthermore, Pearson's correlation analysis showed that synaptophysin had a strong relation with Nrxn1 and Nlgn3 in cerebral cortex and with Nlgn3 in hippocampus. Thus, these findings showed that Nrxn1 and Nlgn3 are differentially expressed in cerebral cortex and hippocampus which might be responsible for alterations in synaptic plasticity during aging.

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“…These changes cannot be attributed to any age-related difference in hippocampal volume because, although a decrease in cortical thickness was observed, we found no evidence of any difference in hippocampal volume in aged, compared with young, rats. However, analysis using a 9.4 Tesla magnet revealed an age-dependent decrease in hippocampal volume of Fisher 344 ϫ Brown Norway hybrid rats (Driscoll et al, 2006), suggesting that there may be strain differences between these rats and the Wistar rats used here, or that the field strength used in this study may not be strong enough to highlight subtle volumetric differences.…”

Section: Discussionmentioning

confidence: 74%

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Blau¹,

Cowley²,

O'Sullivan³

et al. 2012

Neurobiology of Aging

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In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

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The aging hippocampus: A multi-level analysis in the rat

Cited by 198 publications

References 202 publications

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

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