Implications of p75NTR for dentate gyrus morphology and hippocampus-related behavior revisited
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The pan-neurotrophin receptor p75NTR is expressed in the adult brain in a discrete pattern. Although numerous studies have addressed its implications for hippocampal functions, the generated sets of data are surprisingly conflicting. We have therefore set out to re-investigate the impact of a deletion of the full-length p75NTR receptor on several parameters of the dentate gyrus (DG), including neurogenesis and hippocampus-related behavior by using p75NTRExIII knockout mice. Moreover, we investigated further parameters of the DG (cholinergic innervation, dendritic spines). In addition, we analyzed on the morphological level the impact of aging by comparing adult and aged p75NTRExIII mice and their age-matched littermates. Adult (4–6 months old), but not aged (20 months old), p75NTRExIII knockout mice display an enhanced volume of the DG. However, adult neurogenesis within the adult DG was unaffected in both adult and aged p75NTRExIII knockout mice. We could further demonstrate that the change in the volume of the DG was accompanied by an increased cholinergic innervation and increased spine densities of granule cells in adult, but not aged p75NTR deficient mice. These morphological changes in the adult p75NTR deficient mice were accompanied by specific alterations in their behavior, including altered behavior in the Morris water maze test, indicating impairments in spatial memory retention.
KeywordsNeurotrophin p75NTR Adult neurogenesis Dendritic spine Morris water maze Aging
We wish to thank Mrs S. Hanisch for excellent technical assistance. This study was supported by grants (BO 1971/5-1; UN 34/25, SFB 636-TP B3) from the German Research Foundation (DFG).
- Baryshnikova LM, von Bohlen und Halbach O, Kaplan S, von Bartheld CS (2006) Two distinct events, section compression and loss of particles (“lost caps”), contribute to z-axis distortion and bias in optical disector counting. Microsc Res Tech 69(9):738–756. doi: 10.1002/jemt.20345 CrossRefPubMedGoogle Scholar
- Chourbaji S, Hellweg R, Brandis D, Zorner B, Zacher C, Lang UE, Henn FA, Hortnagl H, Gass P (2004) Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. Brain Res Mol Brain Res 121(1–2):28–36. doi: 10.1016/j.molbrainres.2003.11.002 CrossRefPubMedGoogle Scholar
- Freund M, Walther T, von Bohlen Und Halbach O (2013) Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the population of doublecortin positive cells within the dentate gyrus and the piriform cortex. Eur Neuropsychopharmacol. doi: 10.1016/j.euroneuro.2013.06.004 PubMedGoogle Scholar
- Martinowich K, Schloesser RJ, Lu Y, Jimenez DV, Paredes D, Greene JS, Greig NH, Manji HK, Lu B (2012) Roles of p75(NTR), long-term depression, and cholinergic transmission in anxiety and acute stress coping. Biol Psychiatry 71(1):75–83. doi: 10.1016/j.biopsych.2011.08.014 CrossRefPubMedCentralPubMedGoogle Scholar
- Rosch H, Schweigreiter R, Bonhoeffer T, Barde YA, Korte M (2005) The neurotrophin receptor p75NTR modulates long-term depression and regulates the expression of AMPA receptor subunits in the hippocampus. Proc Natl Acad Sci USA 102(20):7362–7367. doi: 10.1073/pnas.0502460102 CrossRefPubMedCentralPubMedGoogle Scholar
- Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, Kraemer RT, Nykjaer A, Hempstead BL (2005) ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci 25(22):5455–5463. doi: 10.1523/jneurosci.5123-04.2005 CrossRefPubMedGoogle Scholar
- von Bartheld C (2002) Counting particles in tissue sections: choices of methods and importance of calibration to minimize biases. Histol Histopathol 17(2):639–648Google Scholar
- von Bohlen und Halbach O, Krause S, Medina D, Sciarretta C, Minichiello L, Unsicker K (2006a) Regional- and age-dependent reduction in trkB receptor expression in the hippocampus is associated with altered spine morphologies. Biol Psychiatry 59(9):793–800. doi: 10.1016/j.biopsych.2005.08.025
- Waltereit R, Leimer U, von Bohlen und Halbach O, Panke J, Holter SM, Garrett L, Wittig K, Schneider M, Schmitt C, Calzada-Wack J, Neff F, Becker L, Prehn C, Kutscherjawy S, Endris V, Bacon C, Fuchs H, Gailus-Durner V, Berger S, Schonig K, Adamski J, Klopstock T, Esposito I, Wurst W, de Angelis MH, Rappold G, Wieland T, Bartsch D (2012) Srgap3−/− mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes. FASEB J 26(11):4418–4428. doi: 10.1096/fj.11-202317