Neuronal and Peripheral Pentraxins Modify Glutamate Release and may Interact in Blood-Brain Barrier Failure.
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present in and around dystrophic neurons in plaques, affecting glutamatergic transmission postsynaptically and mediating effects of amyloidβ. Here, we confirm the presence of NPTX1 around plaques in postmortem Alzheimer's disease brain and report that acutely applied human NPTX1 increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease in glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases paired-pulse ratio, mimicking some of the earliest changes in mice expressing familial Alzheimer's disease genes. The peripheral pentraxin, serum amyloid P component (SAP), causes similar synaptic effects to NPTX1. The presence of SAP on amyloid plaques in Alzheimer's disease confirms that it can enter the brain. We show that SAP and neuronal pentraxins can interact and that SAP can enter the brain if the blood-brain barrier is compromised, suggesting that peripheral pentraxins could affect central synaptic transmission via this interaction, especially in the event of blood-brain barrier breakdown.
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.
Damian M
DM
Cummings
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.
Tiffanie A
TA
Benway
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.|Present address: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Hinze
H
Ho
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.|Present address: Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia.
Angelo
A
Tedoldi
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.
Monica M
MM
Fernandes Freitas
Department of Behavioural Science and Health, University College London, London WC1E 6BT, UK.
Lion
L
Shahab
The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Christina E
CE
Murray
Division of Neuropathology and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK.
Angela
A
Richard-Loendt
Division of Neuropathology and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK.
Sebastian
S
Brandner
The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Tammaryn
T
Lashley
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.
Dervis A
DA
Salih
Department of Neuroscience, Physiology & Pharmacology (NPP), University College London, London WC1E 6BT, UK.
Frances A
FA
Edwards
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D018756:GABA Antagonists; D018698:Glutamic Acid; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D011724:Pyridazines; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C049853:gabazine
Alzheimer's disease; central nervous system; neurodegenerative disease; presynaptic; synaptic plasticity