Loss of thin spines and small synapses contributes to defective hippocampal function in aged mice

Xu, Benke; Sun, Anbang; He, Yun; Qian, Feng; Xi, Shanshan; Long, Dahong; Chen, Yuncai

doi:10.1016/j.neurobiolaging.2018.07.010

Cited by 35 publications

(68 citation statements)

References 73 publications

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“…This decline during the lifetime of the mice is significant as the GZLM analysis showed a significant age effect (Figures 4, 5). These results confirmed that there is an age-related loss of synaptic plasticity in older mice as previously described (Xu et al, 2018). However, we did not observe a significant genotype effect for the thin spines, further corroborating that the decrease in thin spines throughout the lifetime of mice is due to age-related, rather than Aβ-related, alterations in cell function (Figures 4, 5).…”

Section: Elevated Amounts Of Aβ Induce Region-specific Changes In Spisupporting

confidence: 92%

Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression

Hrynchak

Rierola

Golovyashkina

et al. 2020

Front. Synaptic Neurosci.

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Alzheimer's disease is regarded as a synaptopathy with a long presymptomatic phase. Soluble, oligomeric amyloid-β (Aβ) is thought to play a causative role in this disease, which eventually leads to cognitive decline. However, most animal studies have employed mice expressing high levels of the Aβ precursor protein (APP) transgene to drive pathology. Here, to understand how the principal neurons in different brain regions cope with moderate, chronically present levels of Aβ, we employed transgenic mice expressing equal levels of mouse and human APP carrying a combination of three familial AD (FAD)-linked mutations (Swedish, Dutch, and London), that develop plaques only in old age. We analyzed dendritic spine parameters in hippocampal and cortical brain regions after targeted expression of EGFP to allow high-resolution imaging, followed by algorithm-based evaluation of mice of both sexes from adolescence to old age. We report that Aβ species gradually accumulated throughout the life of APP SDL mice, but not the oligomeric forms, and that the amount of membrane-associated oligomers decreased at the onset of plaque formation. We observed an age-dependent loss of thin spines under most conditions as an indicator of a loss of synaptic plasticity in older mice. We further found that hippocampal pyramidal neurons respond to increased Aβ levels by lowering spine density and shifting spine morphology, which reached significance in the CA1 subfield. In contrast, the spine density in cortical pyramidal neurons of APP SDL mice was unchanged. We also observed an increase in the protein levels of PSD-95 and Arc in the hippocampus and cortex, respectively. Our data demonstrated that increased concentrations of Aβ have diverse effects on dendritic spines in the brain and suggest that hippocampal and cortical neurons have different adaptive and compensatory capacity during their lifetime. Our data also indicated that spine morphology differs between sexes in a region-specific manner.

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Section: Elevated Amounts Of Aβ Induce Region-specific Changes In Spisupporting

confidence: 92%

Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression

Hrynchak

Rierola

Golovyashkina

et al. 2020

Front. Synaptic Neurosci.

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“…One of the differences between the young and old synapses is the morphology of dendrite spines. It is known that spines in old brain are usually short in length and are decreased in density, which is believed to contribute to the cognitive impairment [10]. In the present study, we found the difference of spines between young and old rats before and after anesthesia, which could explain the inhibited learning and memory capability of old rats to some degree, as well as suggest the important role of the changes in spine morphology in PND.…”

Section: Discussionsupporting

confidence: 60%

Actin Reorganization in Hippocampal Neurons May Play Roles in Early Impairment of Learning and Memory in Rats After Propofol Anesthesia

Zhang¹,

Li²,

Wu³

2020

Preprint

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Background Perioperative neurocognitive disorder (PND) is a kind of neuronal complication especially observed in elderly patients. The present study was conducted to observe the changes of actin in hippocampus after propofol anesthesia, and to evaluate their roles in consequent learning impairment in both young (3-month-old) and aged (20-month-old) male rats.Methods Double-shuttle box was used to learning evaluation since1, 3, 7 or 14d after anesthesia. Hippocampi were removed after evaluations. F-actin content and the spines were observed through immunofluorescence and laser scanning confocal microscope (LSCM).Results In young rats, latency of escape response (LER) was prolonged within 3 days after anesthesia. However, LER was significantly prolonged until 7days after anesthesia in elderly rats. Moreover, the learning curves were also shift in old rats. Dendritic spines became smaller in anesthesia groups of aged rats within 3 days, where the F-actin contents were significantly increased until 14d post anesthesia.Conclusion Our results indicate that learning ability could be inhibited until after propofol anesthesia especially in old rats. The over-polymerization of actin and the consequent reorganization of dendrite spines in hippocampus may be responsible, which provides fresh evidence in aspect of synaptic plasticity for PND mechanism.

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“…According to the current data, several reports showed that aging caused a reduction in physical activity, including locomotor activity in a novel environment in rodents and humans (Ayers & Verghese, ; Ingram & Jucker, ; Lafoux, Baudry, Bonhomme, Ruyet, & Huchet, ; Yu, Xu, Song, Ji, & Zhang, ). Additionally, some reports have suggested a reduction in spinogenesis and in dendritic length in aged animals (Alcántara‐González et al, , ; Cabrera‐Pedraza et al, ; Diaz et al, ; Hernández‐Hernández et al, ; Juárez et al, ; Sánchez et al, ; Solis‐Gaspar, Vazquez‐Roque, Jesús Gómez‐Villalobos, & Flores, ; Vidal et al, ; Xu et al, ). Furthermore, a recent report about an animal model with premature aging, the spontaneous hypertensive rat, suggests that the structure that is first affected is layer 3 of the PFC, the NAcc, and later the CA1 of the dorsal hippocampus (Sánchez et al, ).…”

Section: Discussionmentioning

confidence: 98%

“…Finally, it is important to clarify that most of these reports involve male animals (Alcántara‐González et al, ; ; Diaz et al, 2017; Hernández‐Hernández et al, ; Juárez et al, ; Vidal et al, ; Xu et al, ). Consequently, it is essential to carry out more research in female organisms about the exact role of aging on dendritic morphology.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, we suggest that pregnancy may be an additional factor in the maintenance of neuronal communication, which allows women to have a higher life expectancy than men. In addition, several recent reports have shown that neuronal communication in rodents at the dendritic level is reduced by aging (Alcántara‐González et al, , ; Juárez, González, Mena, & Flores, ; Xu et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Flores-Vivaldo

Camacho-Ábrego

Picazo

et al. 2019

Synapse

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Pregnancy is a complex process, involving a number of hormones and trophic factors, many of which are formed in the placenta. Several of these trophic factors have an effect at the neuronal level, such as BDNF. Consequently, recent reports have shown that exposure to these hormones (estrogen and progesterone) and trophic factors such as BDNF exert a neuroprotective effect. Here, we study the effect of the number of pregnancies on dendritic morphology of aged female rats (18 months of age). Rats of the 18‐month‐old Sprague Dawley strain with zero, one, two, and three gestations were evaluated for locomotor activity, and Golgi–Cox stain was performed to evaluate the dendritic morphology parameters, the number of dendritic spines, total dendritic length, and branching order number. Adult nulliparous rats (3 months of age) were used as another control group. Adult nulliparous and aging rats with two pregnancies showed an increase in locomotor activity. Adult nulliparous showed an increase in the dendritic spine number compared to old nulliparous rats in both layers of the PFC, the DG, and NAcc. Old rats with two and three pregnancies also showed an increase in the number of dendritic spines compared to old nulliparous rats in layers 3 and 5 of the PFC and in the CA1. Aging animals with one pregnancy also showed an increase in dendritic length compared to old nulliparous rats in the CA1. Our results clearly suggest that two and three pregnancies increase the dendritic spines number in the PFC and CA1 of aged female rats.

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Loss of thin spines and small synapses contributes to defective hippocampal function in aged mice

Cited by 35 publications

References 73 publications

Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression

Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression

Actin Reorganization in Hippocampal Neurons May Play Roles in Early Impairment of Learning and Memory in Rats After Propofol Anesthesia

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

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