The expression of non-clustered protocadherins in adult rat hippocampal formation and the connecting brain regions

Department of Anatomy and Brain Korea 21 Biomedical Science program, Korea University, College of Medicine, Anam-Dong, Sungbuk-Gu, Seoul 136-705, Republic of Korea.
Neuroscience (Impact Factor: 3.36). 09/2010; 170(1):189-99. DOI: 10.1016/j.neuroscience.2010.05.027
Source: PubMed


Non-clustered protocadherins (PCDHs) are calcium-dependent adhesion molecules which have attracted attention for their possible roles in the neuronal circuit formation during development and their implications in the neurological disorders such as autism and mental retardation. Previously, we found that a subset of the non-clustered PCDHs exhibited circuit-dependent expression patterns in thalamo-cortical connections in early postnatal rat brain, but such patterns disappeared in adulthood. In this study, we identified that the non-clustered PCDHs showed differential expression patterns along the septotemporal axis in the subregions of adult hippocampus and dentate gyrus with topographical preferences. The expressions of PCDH1, PCDH9, PCDH10 and PCDH20 showed septal preferences, whereas the expressions of PCDH8, PCDH11, PCDH17 and PCDH19 showed temporal preferences, suggesting that they play roles in the formation/maintenance of intrahippocampal circuits. PCDHs also exhibited the region-specific expression patterns in the areas connected to hippocampal formation such as entorhinal cortex, lateral septum, and basolateral amygdaloid complex. Furthermore, the expression levels of three PCDHs (PCDH8, PCDH19 and PCDH20) were regulated by the electroconvulsive shock stimulation of the brain in the adult hippocampus and dentate gyrus. These results suggest that non-clustered PCDHs are involved in the maintenance and plasticity of adult hippocampal circuitry.

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Available from: Soo-Young Kim, Nov 03, 2014
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    • "Previous research has identified that non-clustered protocadherins (PCDHs) are groups of calcium-dependent adhesion proteins, expressing predominantly in the nervous system. PCDHs play significant roles in neuronal development such as neuronal migration and circuit formation (Yasuda et al., 2007), synaptic plasticity and implications in neurological disorders such as autism and mental retardation (Kim et al., 2010, 2011). In the present study, to comprehensively investigate the BCP-related expression of non-clustered PCDH family members in spinal cord, we examined the expression of all members of non-clustered PCDHs by RT-PCR. "
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    ABSTRACT: The majority of patients with metastatic bone disease experience moderate to severe pain. Bone cancer pain is usually progressive as the disease advances, and is very difficult to treat due to the poor understanding of the underlying mechanisms. Recent studies demonstrated that synaptic plasticity induces spinal cord sensitization and contributes to bone cancer pain. However, whether the synaptic plasticity is due to modifications of existing synapses or the formation of new synaptic connections is still unknown. Here we showed that a carcinoma implantation into a rats' tibia induced a significant increase in the number of excitability synapses in the dorsal horn, which contributes to the development of bone cancer pain. Previous studies identified that non-clustered protocadherins play significant roles in neuronal development and other implications in neurological disorders. In the present study, we showed that Protocadherin20 was significantly increased in the dorsal horn of cancer-bearing rats, while knockdown of Protocadherin20 with RNAi lentivirus reversed bone cancer-induced pain behaviors and decreased excitatory synaptogenesis in ipsilateral dorsal horn. In an in vitro study, we showed that knockdown of Protocadherin20 inhibited neurite outgrowth and excitatory synapse formation of dorsal neurons. These findings indicate that Protocadherin20 is required for the development of bone cancer pain probably by promoting the excitability synaptogenesis.
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    • "The pattern of expression in the developing human cortex was similar to that reported in the ferret (Krishna-K et al. 2009) and the rat (Kim et al. 2007), and our findings of expression in the adult hippocampal formation and amygdala are similar to observations made in the rat (Kim et al. 2010) and mouse (Hertel et al. 2008). Reports of Pcdh11 expression in the cortex of adult experimental animals are less consistent: Ranging from complete absence in rat (Kim et al. 2007), a subpopulation of neurons in layers IV–VI in the mouse somatosensory cortex (Krishna-K et al. 2011), to layers II–VI of the mouse motor cortex (Hertel and Redies 2011), and layers II– VI of the ferret visual cortex (Krishna-K et al. 2009). "
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    ABSTRACT: Protocadherins 11X and 11Y are cell adhesion molecules of the δ1-protocadherin family. Pcdh11X is present throughout the mammalian radiation; however, 6 million years ago (MYA), a reduplicative translocation of the Xq21.3 block onto what is now human Yp11 created the Homo sapiens-specific PCDH11Y. Therefore, modern human females express PCDH11X whereas males express both PCDH11X and PCDH11Y. PCDH11X/Y has been subject to accelerated evolution resulting in human-specific changes to both proteins, most notably 2 cysteine substitutions in the PCDH11X ectodomain that may alter binding characteristics. The PCDH11X/Y gene pair is postulated to be critical to aspects of human brain evolution related to the neural correlates of language. Therefore, we raised antibodies to investigate the temporal and spatial expression of PCDH11X/Y in cortical and sub-cortical areas of the human fetal brain between 12 and 34 postconceptional weeks. We then used the antibodies to determine if this expression was consistent in a series of adult brains. PCDH11X/Y immunoreactivity was detectable at all developmental stages. Strong expression was detected in the fetal neocortex, ganglionic eminences, cerebellum, and inferior olive. In the adult brain, the cerebral cortex, hippocampal formation, and cerebellum were strongly immunoreactive, with expression also detectable in the brainstem.
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    • "We next performed in situ hybridization of Pcdh11X using another mammalian species, i.e., the mouse, in order to examine whether the expression pattern in the marmoset brain was conserved in other mammalian species. We found clear Pcdh11X staining with the antisense probe, as has been previously reported in mice [1], [2], [30], [31] and rats [32], [33], but no clear staining was seen with the sense probe. "
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    ABSTRACT: Background Protocadherin-11 is a cell adhesion molecule of the cadherin superfamily. Since, only in humans, its paralog is found on the Y chromosome, it is expected that protocadherin-11X/Y plays some role in human brain evolution or sex differences. Recently, a genetic mutation of protocadherin-11X/Y was reported to be associated with a language development disorder. Here, we compared the expression of protocadherin-11 X-linked in developing postnatal brains of mouse (rodent) and common marmoset (non-human primate) to explore its possible involvement in mammalian brain evolution. We also investigated its expression in the Bengalese finch (songbird) to explore a possible function in animal vocalization and human language faculties. Methodology/Principal Findings Protocadherin-11 X-linked was strongly expressed in the cerebral cortex, hippocampus, amygdala and brainstem. Comparative analysis between mice and marmosets revealed that in certain areas of marmoset brain, the expression was clearly enriched. In Bengalese finches, protocadherin-11 X-linked was expressed not only in nuclei of regions of the vocal production pathway and the tracheosyringeal hypoglossal nucleus, but also in areas homologous to the mammalian amygdala and hippocampus. In both marmosets and Bengalese finches, its expression in pallial vocal control areas was developmentally regulated, and no clear expression was seen in the dorsal striatum, indicating a similarity between songbirds and non-human primates. Conclusions/Significance Our results suggest that the enriched expression of protocadherin-11 X-linked is involved in primate brain evolution and that some similarity exists between songbirds and primates regarding the neural basis for vocalization.
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