P75 neurotrophin receptor regulates expression of neural cell adhesion molecule 1

Korade, Željka; Yan, Chaohua; Portugal, Carmel; Kim, Tae‐Wan; Saragovi, H. Uri; Sisodia, Sangram S.; Mirnics, Károly; Schor, Nina F.

doi:10.1016/j.nbd.2005.06.004

Cited by 22 publications

(14 citation statements)

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“…The normal time at which the abundance and localization of p75NTR expression change coincides with the time of loss of language function and onset of noticeably aberrant social interactions in children with autism. 7,8,13 By the age of 2 years in human, its expression is limited to the hippocampus, cholinergic basal forebrain and cerebellum (particularly the external granular and the Purkinje cell layers). 8,13,19 All of these regions have been implicated in autism.…”

Section: Discussionmentioning

confidence: 99%

“…7,8,13 By the age of 2 years in human, its expression is limited to the hippocampus, cholinergic basal forebrain and cerebellum (particularly the external granular and the Purkinje cell layers). 8,13,19 All of these regions have been implicated in autism. Recent studies of others have implicated the cerebellum, and particularly abnormalities of the cerebellar vermis, in autistic behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…25 We have similarly reported that changed gene expression in p75NTR-positive versus p75NTR-negative PC12 cells demonstrates the same functional groups, including genes responsible for apoptosis induction and prevention; genes that code for mediators of inflammation that also have a role in inflammatory and neuroblastic cell cycling and differentiation; genes that code for the enzymes involved in de novo cholesterol synthesis; and genes that code for NCAMs. 8,13 …”

Section: Discussionmentioning

confidence: 99%

“…15 Our studies of genes that are coordinately regulated with p75NTR demonstrated the relationship between expression of p75NTR and expression of the neural cell adhesion molecules, NCAM and L1. 13 In addition, a high-density single nucleotide polymorphism study implicated chromosome 17q21 and the CACNA1G gene in autism. 30 The NGFR gene, which codes for p75NTR, is located at chromosome 17q21–22, and may be a viable candidate gene, as well.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, we and others have shown that p75NTR exhibits many of the characteristics one would predict are exhibited by molecular mediators of autism (see Table 1). 7, 8, 9, 10, 11, 12, 13 We now demonstrate that knockout of the p75 neurotrophin receptor (p75NTR) from cerebellar Purkinje cells of mice results in autism-like stereotypies, diminished social interaction, decreased interest in novel environments and decreased complexity of the dendritic arborization of cerebellar Purkinje cells.…”

Section: Introductionmentioning

confidence: 93%

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Cerebellar Purkinje cell p75 neurotrophin receptor and autistic behavior

et al. 2014

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The p75 neurotrophin receptor (p75NTR) is normally expressed in cerebellar Purkinje cells throughout the lifespan. Children with autism spectrum behavior exhibit apparent cerebellar Purkinje cell loss. Cerebellar transcriptome changes seen in the murine prenatal valproate exposure model of autism include all of the proteins known to constitute the p75NTR interactome. p75NTR is a modulator of cytoplasmic and mitochondrial redox potential, and others have suggested that aberrant response to oxidant stress has a major role in the pathogenesis of autism. We have created Purkinje cell-selective p75NTR knockout mice that are the progeny of hemizygous Cre-Purkinje cell protein 2 C57Bl mice and p75NTR floxed C57Bl mice. These Cre-loxP mice exhibit complete knockout of p75NTR in ~50% of the cerebellar Purkinje cells. Relative to Cre-only mice and wild-type C57Bl mice, this results in a behavioral phenotype characterized by less allogrooming of (P<0.05; one-way analysis of variance) and socialization or fighting with (each P<0.05) other mice; less (1.2-fold) non-ambulatory exploration of their environment than wild-type (P<0.01) or Cre only (P<0.01) mice; and almost twofold more stereotyped jumping behavior than wild-type (P<0.05) or Cre (P<0.02) mice of the same strain. Wild-type mice have more complex dendritic arborization than Cre-loxP mice, with more neurites per unit area (P<0.025, Student's t-test), more perpendicular branches per unit area (P<0.025) and more short branches/long neurite (P<0.0005). Aberrant developmental regulation of expression of p75NTR in cerebellar Purkinje cells may contribute to the pathogenesis of autism.

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