Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity

Benice, Ted S.; Rizk, Angela; Kohama, Steven G.; Pfankuch, Timothy; Raber, Jacob

doi:10.1016/j.neuroscience.2005.08.029

Cited by 220 publications

(212 citation statements)

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“…Pearson's correlation analysis showed a positive correlation of synaptophysin expression with Nrxn1 and Nlgn3 in cerebral cortex and hippocampus. Similar to Nlgn3, the level of synaptophysin also increased in old hippocampus as also reported earlier (Benice et al 2006). In this study, it has been suggested that increased synaptophysin may be involved in a mechanism by which hippocampus might compensate agerelated functional deficits (Benice et al 2006).…”

Section: Discussionsupporting

confidence: 88%

“…Similar to Nlgn3, the level of synaptophysin also increased in old hippocampus as also reported earlier (Benice et al 2006). In this study, it has been suggested that increased synaptophysin may be involved in a mechanism by which hippocampus might compensate agerelated functional deficits (Benice et al 2006). In another study, increased synaptophysin expression has been reported to be involved in a compensatory response to amyloid precursor protein-derived (King and Arendash 2002).…”

Section: Discussionsupporting

confidence: 87%

“…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%

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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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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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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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“…Therefore, it is concluded that there is a modification of the density of the tested proteins associated with the vesicular release apparatus which might slightly increase during adulthood and then significantly decreases upon aging. This age-related decrease of presynaptic markers is in general agreement with the majority of studies reporting a decrease in synaptophysin mRNA and protein density and in the number of elements immuno-positive for synaptophysin with aging in the hippocampus and various cortical structures (Chen et al, 1995;Eastwood et al, 1994;Frick and Fernandez, 2003;King and Arendash, 2002;Masliah et al, 1993;Rutten et al, 2005;Saito et al, 1994), albeit some studies reported lack of modification (Calhoun et al, 1998;Eastwood et al, 2006;Nicolle et al, 1999a) and even increases (Benice et al, 2006;Himeda et al, 2005) in the density of this presynaptic marker.…”

Section: Resultssupporting

confidence: 88%

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Canas

Duarte

Rodrigues

et al. 2009

Neurobiology of Aging

121

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Please cite this article in press as: Canas, P.M., et al., Modification upon aging of the density of presynaptic modulation systems in the hippocampus, Neurobiol Aging (2008) Abstract Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A 1 and CB 1 receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A 2A receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory presynaptic modulation systems.

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“…A modified version of the Morris water maze [3,12] was used to assess spatial learning and memory. A circular pool (diameter 140 cm) was filled with opaque water (24°C) and mice were trained to locate a submerged platform in order to escape from the water (luminescence: 40 lx).…”

mentioning

confidence: 99%

Impairments in spatial memory retention of GFAP-apoE4 female mice

Meer

Acevedo

Raber

2007

Behavioural Brain Research

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The human apolipoprotein E isoforms, apoE2, apoE3, and apoE4, have differential effects on brain function. Compared to apoE3, apoE4 increases the risk of age-related cognitive decline in humans and female mice expressing apoE in neurons. Here we show impaired spatial memory retention in female mice expressing apoE4 in astrocytes compared to those expressing apoE3 in astrocytes or lacking apoE. Thus, apoE4 impairs cognition whether expressed in neurons or astrocytes. Keywordswater maze; passive avoidance; rotorod; apolipoprotein E; transgenic miceHuman apolipoprotein E is a protein encoded by three distinct alleles: ε2, ε3 and ε4. The major resulting proteins, apoE2, apoE3 and apoE4 play an important role in the redistribution and metabolism of lipoproteins and cholesterol. In the brain, apoE is involved in development, regeneration, neurite extension and neuroprotection [11]. ApoE is associated with the pathological hallmarks of Alzheimer's disease (AD) and the severity of AD pathology is influenced by APOE genotype. ApoE4 also has detrimental effects on AD-like pathology in patients with other conditions, including progressive nuclear palsy [20] and Down's syndrome [4]. The detrimental effects of apoE4 are not limited to AD. Compared to apoE3, apoE4 also increases the risk of developing cognitive impairments after neurotrauma, ischemia, cardiopulmonary bypass surgery, human immunodeficiency virus infection, and cognitive impairments that occur with the normal aging and in the context of Parkinson's disease (for review, [15]). Various mechanisms have been proposed to mediate the differential effects of apoE isoforms on brain function, including effects on cholesterol transport, the metabolism amyloid β peptide, cell signaling by lipoprotein receptors, on proteolysis of apoE, and androgen receptor function (for review, [15]). Most synthesis of apoE in the brain takes place in glial cells, in particular astrocytes. However, neurons are also able to generate apoE, particularly following injury [1,5,8,21,22]. In addition, apoE can be secreted from astrocytes and be taken up by neurons. The cellular source of apoE might be important for isoform-dependent effects of apoE on brain function. Proteolytic apoE fragments and tangle-like inclusions were seen

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Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity

Cited by 220 publications

References 45 publications

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

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

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Impairments in spatial memory retention of GFAP-apoE4 female mice

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