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Comment
. 2017 Apr 25:6:e26942.
doi: 10.7554/eLife.26942.

Identifying faulty brain circuits

Jesse E Hanson  1
Affiliations
Comment

Identifying faulty brain circuits

Jesse E Hanson. Elife. .

Abstract

A protein called NPTX2 may be a useful marker of neural circuit defects in patients with Alzheimer's disease.

Keywords: Alzheimer's disease; dementia; human; immediate early gene; inhibitory neuron; mouse; neuroscience.

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Conflict of interest statement

The author declares that no competing interests exist.

Figures

Figure 1.
Figure 1.. Parvalbumin interneurons in Alzheimer’s disease.
Parvalbumin interneurons (PV interneuron) connect to excitatory neurons in the forebrain (top). In healthy individuals (control; left), the NPTX2 protein (red) arranges GluA4-containing AMPA receptors (blue) in clusters at these connections. As a result, electrical signals from the excitatory neurons strongly activate the interneurons. A sodium channel called Nav1.1 (black) in the interneurons helps to generate electrical signals that inhibit other neurons in the circuit. In the brains of individuals with Alzheimer’s disease (right), the levels of NPTX2, GluA4 and Nav1.1 are all lower than in healthy individuals; this leads to less inhibitory interneuron activity. Other neurons in the circuit thus become more active than they should be, resulting in defects in circuit function and cognitive impairments. NPTX2 can also be detected in the cerebrospinal fluid (CSF; bottom). Individuals with Alzheimer’s disease (right) have less NPTX2 in their CSF compared to healthy individuals (control; left). NPTX2 levels in CSF correlate with cognitive impairments.
See this image and copyright information in PMC

Comment on

  • NPTX2 and cognitive dysfunction in Alzheimer's Disease.
    Xiao MF, Xu D, Craig MT, Pelkey KA, Chien CC, Shi Y, Zhang J, Resnick S, Pletnikova O, Salmon D, Brewer J, Edland S, Wegiel J, Tycko B, Savonenko A, Reeves RH, Troncoso JC, McBain CJ, Galasko D, Worley PF. Xiao MF, et al. Elife. 2017 Mar 23;6:e23798. doi: 10.7554/eLife.23798. Elife. 2017. PMID: 28440221 Free PMC article.

References

    1. Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL, Gallagher M. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron. 2012;74:467–474. doi: 10.1016/j.neuron.2012.03.023. - DOI - PMC - PubMed
    1. Chang MC, Park JM, Pelkey KA, Grabenstatter HL, Xu D, Linden DJ, Sutula TP, McBain CJ, Worley PF. Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. Nature Neuroscience. 2010;13:1090–1097. doi: 10.1038/nn.2621. - DOI - PMC - PubMed
    1. Gu Y, Huang S, Chang MC, Worley P, Kirkwood A, Quinlan EM. Obligatory role for the immediate early gene NARP in critical period plasticity. Neuron. 2013;79:335–346. doi: 10.1016/j.neuron.2013.05.016. - DOI - PMC - PubMed
    1. Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016;540:230–235. doi: 10.1038/nature20587. - DOI - PMC - PubMed
    1. Palop JJ, Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nature Reviews Neuroscience. 2016;17:777–792. doi: 10.1038/nrn.2016.141. - DOI - PMC - PubMed