Age-Related Changes in the Synapses of the Rat' Neostriatum

Itzev, Dimitar E.; Lolova, I; Lolov, S.; Usunoff, Kamen G.

doi:10.1076/apab.109.1.80.4279

Cited by 12 publications

(3 citation statements)

References 67 publications

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“…In the present study, we extended this finding to include the presynaptic compartment, and showed a proportional increase in axon terminal diameter. Similar increases in axon terminal size have been previously described in the neostriatum and cortex of aged rodents (Itzev, Lolova, Lolov, & Usunoff, ; Mostany et al, ). Age‐dependent alterations to morphology, such as swelling, could potentially contribute to axon terminal enlargement (Cork et al, ; Peters & Sethares, ).…”

Section: Discussionsupporting

confidence: 83%

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Crimins

Puri

Calakos

et al. 2018

J of Comparative Neurology

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Female rhesus monkeys and women are subject to age‐ and menopause‐related deficits in working memory, an executive function mediated by the dorsolateral prefrontal cortex (dlPFC). Long‐term cyclic administration of 17β‐estradiol improves working memory, and restores highly plastic axospinous synapses within layer III dlPFC of aged ovariectomized monkeys. In this study, we tested the hypothesis that synaptic distributions of tau protein phosphorylated at serine 214 (pS214‐tau) are altered with age or estradiol treatment, and couple to working memory performance. First, ovariectormized young and aged monkeys received vehicle or estradiol treatment, and were tested on the delayed response (DR) test of working memory. Serial section electron microscopic immunocytochemistry was then performed to quantitatively assess the subcellular synaptic distributions of pS214‐tau. Overall, the majority of synapses contained pS214‐tau immunogold particles, which were predominantly localized to the cytoplasm of axon terminals. pS214‐tau was also abundant within synaptic and cytoplasmic domains of dendritic spines. The density of pS214‐tau immunogold within the active zone, cytoplasmic, and plasmalemmal domains of axon terminals, and subjacent to the postsynaptic density within the subsynaptic domains of dendritic spines, were each reduced with age. None of the variables examined were directly linked to cognitive status, but a high density of pS214‐tau immunogold particles within presynaptic cytoplasmic and plasmalemmal domains, and within postsynaptic subsynaptic and plasmalemmal domains, accompanied high synapse density. Together, these data support a possible physiological, rather than pathological, role for pS214‐tau in the modulation of synaptic morphology in monkey dlPFC.

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Section: Discussionsupporting

confidence: 83%

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Crimins

Puri

Calakos

et al. 2018

J of Comparative Neurology

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“…In fact, it should be noted that the volume and amount of protein associated with nerve terminals is expected to be several‐fold lower than other neuronal compartments like dendrites (Rusakov et al . 1998; Itzev et al . 2001).…”

Section: Discussionmentioning

confidence: 99%

“…However, the observation that there was a lower density of A 2A and mGluR5 receptors located in glutamatergic nerve terminals does not necessarily mean that the modulation of glutamate release by A 2A and mGluR5 receptors might represent a minor action of these receptors in the striatum. In fact, it should be noted that the volume and amount of protein associated with nerve terminals is expected to be several-fold lower than other neuronal compartments like dendrites (Rusakov et al 1998;Itzev et al 2001). Therefore, when considering receptors that are located both pre-and postsynaptically, it is always expected that they should be more abundant postsynaptically because of the larger volume showing that there is a co-localization of mGluR5 and A 2A receptors in nearly 50% of the glutamatergic nerve terminals (identified as vGluT1 and vGluT2 immunoreactive).…”

Section: Discussionmentioning

confidence: 99%

Co‐localization and functional interaction between adenosine A_2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum

Rodrigues

Alfaro

Rebola

et al. 2004

Journal of Neurochemistry

188

155

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The anti-Parkinsonian effect of glutamate metabotropic group 5 (mGluR5) and adenosine A 2A receptor antagonists is believed to result from their ability to postsynaptically control the responsiveness of the indirect pathway that is hyperfunctioning in Parkinson's disease. mGluR5 and A 2A antagonists are also neuroprotective in brain injury models involving glutamate excitotoxicity. Thus, we hypothesized that the antiParkinsonian and neuroprotective effects of A 2A and mGluR5 receptors might be related to their control of striatal glutamate release that actually triggers the indirect pathway. The A 2A agonist, CGS21680 (1-30 nM) facilitated glutamate release from striatal nerve terminals up to 57%, an effect prevented by the A 2A antagonist, SCH58261 (50 nM). The mGluR5 agonist, CHPG (300-600 lM) also facilitated glutamate release up to 29%, an effect prevented by the mGluR5 antagonist, MPEP (10 lM). Both mGluR5 and A 2A receptors were located in the active zone and 57 ± 6% of striatal glutamatergic nerve terminals possessed both A 2A and mGluR5 receptors, suggesting a presynaptic functional interaction. Indeed, submaximal concentrations of CGS21680 (1 nM) and CHPG (100 lM) synergistically facilitated glutamate release and the facilitation of glutamate release by 10 nM CGS21680 was prevented by 10 lM MPEP, whereas facilitation by 300 lM CHPG was prevented by 10 nM SCH58261. These results provide the first direct evidence that A 2A and mGluR5 receptors are co-located in more than half of the striatal glutamatergic terminals where they facilitate glutamate release in a synergistic manner. This emphasizes the role of the modulation of glutamate release as a likely mechanism of action of these receptors both in striatal neuroprotection and in Parkinson's disease.

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Pre‐ and postsynaptic contributions to age‐related alterations in corticostriatal synaptic plasticity

Akopian

Walsh

2006

Synapse

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Aging creates deficits in motor performance related to changes in striatal processing of cortical information. This study describes age-related changes in corticostriatal snaptic plasticity and associated mechanisms, which may contribute to declines in motor behavior. Intracellular recordings revealed an age-related decrease in the expression of paired-pulse, posttetanic, and long-term potentiation (LTP). The age-related difference in LTP was associated with reduced sensitivity to block of N-methyl-D-aspartate (NMDA) receptors in the aged population. These age-related changes could not be explained by increased L-type Ca(2+)channel activity, since block of L-type Ca(2+) channels with nifedipine increased rather than decreased the age-related difference in long-term plasticity. Age-related increases in reactive oxygen species (ROS) modulation were also ruled out, since application of H(2)O(2) produced changes in synaptic function that were opposite to trends seen in aging, and addition of the antioxidant Trolox-C had a larger effect on long-term plasticity in young rats than in older rats. A robust age-related difference in long-term synaptic plasticity was found by studying synaptic plasticity following the blocking of D2 receptors with l-sulpiride, which may involve age-difference in NMDA receptor function. l-sulpiride consistently enabled a slow development of LTP at young (but not aged) corticostriatal synapses. However, No age differences were found in the sensitivity to the addition of the D2 receptor agonist quinpirole. These findings provide evidence for age-induced changes in the release properties of cortical terminals and in the functioning of postsynaptic striatal NMDA receptors, which may contribute to age-related deficits in striatum control of movement.

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Age-Related Changes in the Synapses of the Rat' Neostriatum

Cited by 12 publications

References 67 publications

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Co‐localization and functional interaction between adenosine A_2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum

Pre‐ and postsynaptic contributions to age‐related alterations in corticostriatal synaptic plasticity

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Age-Related Changes in the Synapses of the Rat' Neostriatum

Cited by 12 publications

References 67 publications

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Co‐localization and functional interaction between adenosine A2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum

Pre‐ and postsynaptic contributions to age‐related alterations in corticostriatal synaptic plasticity

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Co‐localization and functional interaction between adenosine A_2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum