Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior

Ruan, Chun-Sheng; Yang, Chunrui; Li, Jiayi; Hy, Luo; Bobrovskaya, Larisa; Zhou, Xin‐Fu

doi:10.1016/j.expneurol.2016.04.015

Cited by 24 publications

(23 citation statements)

References 63 publications

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“…We validated the specificity of the sortilin antibodies to the extracellular (goat) and intracellular C-terminal (rabbit) parts using sortilin knockout (−/−) and wildtype (+/+) mouse brains (Figures 1A–E; Ruan et al, 2016). Both antibodies marked a ~100 kDa band in immunoblot of sortilin+/+, but not −/−, lysates, representing a presence of the full-length protein in the wild-type but not knockout mouse tissues (Figures 1B,D).…”

Section: Resultsmentioning

confidence: 99%

“…Through this latter approach, brain samples/cases exhibiting a spectrum of AD-type neuropathology were used to allow a correlated morphometric analysis on Aβ and sortilin pathologies. Brains from sortilin knockout (−/−, n = 4), wildtype (+/+, n = 4) and C57BL/6 mice were used for the purpose of antibody validation (Ruan et al, 2016), with hemi-brains obtained after vascular rinse with cold saline then prepared for immunohistochemistry and immunoblot, respectively. The use of postmodern human brains and laboratory animals was approved by the Ethics Committees of Central South University Xiangya School of Medicine and Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences (human brain study), and the Animal Ethic Committee of SA Pathology at Adelaide, Australia (mouse brain study), in compliance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) and the National Institutes of Health Guide for the Care and Use of Laboratory Animals.…”

Section: Methodsmentioning

confidence: 99%

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Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum

et al. 2017

Front. Neuroanat.

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Genetic variations in the vacuolar protein sorting 10 protein (Vps10p) family have been linked to Alzheimer’s disease (AD). Here we demonstrate deposition of fragments from the Vps10p member sortilin at senile plaques (SPs) in aged and AD human cerebrum. Sortilin changes were characterized in postmortem brains with antibodies against the extracellular and intracellular C-terminal domains. The two antibodies exhibited identical labeling in normal human cerebrum, occurring in the somata and dendrites of cortical and hippocampal neurons. The C-terminal antibody also marked extracellular lesions in some aged and all AD cases, appearing as isolated fibrils, mini-plaques, dense-packing or circular mature-looking plaques. Sortilin and β-amyloid (Aβ) deposition were correlated overtly in a region/lamina- and case-dependent manner as analyzed in the temporal lobe structures, with co-localized immunofluorescence seen at individual SPs. However, sortilin deposition rarely occurred around the pia, at vascular wall or in areas with typical diffuse Aβ deposition, with the labeling not enhanced by section pretreatment with heating or formic acid. Levels of a major sortilin fragment ~15 kDa, predicted to derive from the C-terminal region, were dramatically elevated in AD relative to control cortical lysates. Thus, sortilin fragments are a prominent constituent of the extracellularly deposited protein products at SPs in human cerebrum.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum

et al. 2017

Front. Neuroanat.

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“…Furthermore, the authors describe the effect observed as being consistent with a hyperactive and anxiety behaviour, as Sort1 or Sortilin are involved in a number of mood disorders generated at hippocampal and cortex level (Ruan et al . ). We have previously reported that maternal exposure to constant light affects spatial memory in the adult rat, an effect accompanied by changes in hippocampus expression of NMDA subunits and abnormal corticosterone levels (Vilches et al .…”

Section: Discussionmentioning

confidence: 97%

Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function

Salazar

Richter

Spichiger

et al. 2018

The Journal of Physiology

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Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long-term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down-regulated and 437 up-regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48-20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long-term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.

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“…Adding to the complexity, our group established that SorCS2 exists in two different isoforms in the adult, with the single chain variant mediating the response mentioned above, while the two‐chain variant takes part in pro‐NGF mediated apoptosis (Glerup et al, ). Despite their overlapping ligands the phenotype of sortilin(−/−) and SorCS2(−/−) mice differs significantly (Glerup et al, ; Ruan et al, ). A function of SorCS2 in adult mice has recently been elucidated, namely the indispensable requirement for SorCS2 in hippocampal NMDA‐receptor dependent synaptic plasticity (Glerup et al, ).…”

Section: Introductionmentioning

confidence: 99%

Highly segregated localization of the functionally related vps10p receptors sortilin and SorCS2 during neurodevelopment

Boggild

Mølgaard

Glerup

et al. 2018

J of Comparative Neurology

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Nervous system development is a precisely orchestrated series of events requiring a multitude of intrinsic and extrinsic cues. Sortilin and SorCS2 are members of the Vps10p receptor family with complementary influence on some of these cues including the neurotrophins (NTs). However, the developmental time points where sortilin and SorCS2 exert their activities in conjunction or independently still remain unclear. In this study we present the characterization of the spatiotemporal expression pattern of sortilin and SorCS2 in the developing murine nervous system. Sortilin is highly expressed in the fetal nervous system with expression localized to distinct cell populations. Expression was high in neurons of the cortical plate and developing allocortex, as well as subpallial structures. Furthermore, the neuroepithelium lining the ventricles and the choroid plexus showed high expression of sortilin, together with the developing retina, spinal ganglia, and sympathetic ganglia. In contrast, SorCS2 was confined in a marked degree to the thalamus and, at E13.5, the floor plate from midbrain rostrally to spinal cord caudally. SorCS2 was also found in the ventricular zones of the ventral hippocampus and nucleus accumbens areas, in the meninges and in Schwann cells. Hence, sortilin and SorCS2 are extensively present in several distinct anatomical areas in the developing nervous system and are rarely co-expressed. Possible functions of sortilin and SorCS2 pertain to NT signaling, axon guidance and beyond. The present data will form the basis for hypotheses and study designs for unravelling the functions of sortilin and SorCS2 during the establishment of neuronal structures and connections.

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Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior

Cited by 24 publications

References 63 publications

Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum

Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum

Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function

Highly segregated localization of the functionally related vps10p receptors sortilin and SorCS2 during neurodevelopment

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