EMAIL THIS PAGE TO A FRIEND

The Journal of clinical investigation

Neurotrophin receptor p75(NTR) mediates Huntington's disease-associated synaptic and memory dysfunction.


PMID 25180603

Abstract

Learning and memory deficits are early clinical manifestations of Huntington's disease (HD). These cognitive impairments have been mainly associated with frontostriatal HD pathology; however, compelling evidence provided by several HD murine models suggests that the hippocampus may contribute to synaptic deficits and memory dysfunction in HD. The neurotrophin receptor p75(NTR) negatively regulates spine density, which is associated with learning and memory; therefore, we explored whether disturbed p75(NTR) function in the hippocampus could contribute to synaptic dysfunction and memory deficits in HD. Here, we determined that levels of p75(NTR) are markedly increased in the hippocampus of 2 distinct mouse models of HD and in HD patients. Normalization of p75(NTR) levels in HD mutant mice heterozygous for p75(NTR) prevented memory and synaptic plasticity deficits and ameliorated dendritic spine abnormalities, likely through normalization of the activity of the GTPase RhoA. Moreover, viral-mediated overexpression of p75(NTR) in the hippocampus of WT mice reproduced HD learning and memory deficits, while knockdown of p75(NTR) in the hippocampus of HD mice prevented cognitive decline. Together, these findings provide evidence of hippocampus-associated memory deficits in HD and demonstrate that p75(NTR) mediates synaptic, learning, and memory dysfunction in HD.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1405514
Anti-BDNF antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
B9186 Anti-Brain-derived Neurotrophic Factor antibody produced in chicken, affinity isolated antibody, lyophilized powder
SAB2501257
Anti-CAMK2A antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1405553
Anti-CAMK2A antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2501245
Anti-DLG4 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1405717
Anti-DLG4 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA010122
Anti-DLG4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1401115
Anti-DLG4 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB2105773
Anti-DLG4 antibody produced in rabbit, affinity isolated antibody
SAB1402127
Monoclonal Anti-BDNF antibody produced in mouse, clone 1B10, purified immunoglobulin, buffered aqueous solution
B5050 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 35928.11, purified immunoglobulin, lyophilized powder
B9436 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 37141, purified immunoglobulin, lyophilized powder
B9561 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 35909, purified immunoglobulin, lyophilized powder
B9686 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 37129, purified immunoglobulin, lyophilized powder
WH0000815M1
Monoclonal Anti-CAMK2A antibody produced in mouse, clone 2C4, purified immunoglobulin, buffered aqueous solution
SAB1403629
Monoclonal Anti-CAMK2A antibody produced in mouse, clone 2C12, purified immunoglobulin, buffered aqueous solution
SAB5200002
Monoclonal Anti-DLG4 antibody produced in mouse, clone 6G6, 1 mg/mL, purified immunoglobulin
SAB5200003
Monoclonal Anti-DLG4 antibody produced in mouse, clone 7E3, 1 mg/mL, purified immunoglobulin
P246
Monoclonal Anti-PSD95 antibody produced in mouse, clone 7E3-1B8, purified immunoglobulin, buffered aqueous solution