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http://ahmadsalehi.yolasite.com Translational Psychiatry (2011) 1, e51; doi:10.1038/tp.2011.47 BDNF polymorphism predicts the rate of decline in skilled task performance and hippocampal volume in healthy individualsM Millan Sanchez, D Das, J L Taylor, A Noda, J A Yesavage and A Salehi Download the full text at: http://www.nature.com/tp/journal/v1/n10/full/tp201147a.html Covered by: PsychCentral.com - Oct 26, 2011 Science News Stanford Scope The Telegraph Schematic representation of possible mechanism by which val66met substitution in BDNF leads to failed activity-dependent release of BDNF or reduced intracellular transport. Val66met substitution changes the dynamics of interaction between BDNF and two important proteins: (1) Sortilin, is involved in intracellular sorting and pro-neurotrophin signaling. Val66met substitution leads to reduction of BDNF interaction with this protein, which results in mis-sorting into the constitutive secretory pathway instead of activity-dependent release. (2) Translin is a highly conserved protein involved in mRNA transport. An exon found in all BDNF mRNA splice variants contains a specific translin-binding region, which is essential for appropriate BDNF mRNA dendritic targeting. It has been shown that Val66met substitution diminishes BDNF mRNA interaction with translin, which leads to reduced translocation of BDNF mRNA to dendrites. Neurobiological Elements of Cognitive Dysfunction in Down Syndrome: Exploring the Role of APP.Please click on the cover to access the full text.  ONLINE COVER Three copies of human chromosome 21. People that carry an extra copy of chromosome 21 have Down syndrome, a disorder characterized by learning and cognitive difficulties, among other symptoms. Mice with a similar genetic abnormality also have learning difficulties and, as shown by Salehi et al., degeneration in a brain nucleus that uses norepinephrine as a neurotransmitter. Restoration of neurotransmitter concentrations can also restore the learning difficulties, suggesting that a similar approach in individuals with Down syndrome may prove therapeutically useful. [CREDIT: C. BICKEL/AAAS] Restoration of Norepinephrine-Modulated Contextual Memory in a
Mouse Model of Down SyndromeA. Salehi, M. Faizi, D. Colas, J. Valletta, J. Laguna, R. Takimoto-Kimura, A. Kleschevnikov, S. L. Wagner, P. Aisen, M. Shamlooand W. C. Mobley Read the coverage of this paper by:
Alzforum Science Stanford Medical Center Science Daily MIT Technology Review Times Online Scientist Neurology Today  Health 24 Le Figaro Le Monde Stanford Medicine Lucile Packard Children's Hospital at Stanford Down Syndrome Research Center at Stanford Scope Citation Record
 On the cover: Neurodegeneration of purkinje cells. In a mouse model of neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disorder, accumulation of lipofuscin granules is followed by progressive neuronal cell death. Purkinje neurons in the cerebellum are severely affected as illustrated by loss of cell bodies and dendritic arbors. Massive lipofuscin deposits remain in the purkinje cell layer in the degenerating brain. The work by Tamaki et al. (pages 310–319) demonstrates that transplantation of human neural stem cells leads to neuroprotection of host cells in the NCL mouse brain. The cover image shows a section of cerebellum from a mouse with disease symptoms. Cover design by Monika Dohse.
 Alzheimer's is characterized by short-term memory loss and plaques and tangles in the cerebral cortex. Aberrant ubiquitin protein, likely resulting from an RNA mutation, is detectable in plaques (vague spots) and tangles (flame shapes, ~40 µm long) in the hippocampus (a region involved in short-term memory) from an Alzheimer's patient. This mutation mechanism is likely a factor in nonfamilial Alzheimer's and other neurodegenerative pathologies. See p. 242 and the News story on p. 174. [Image: F. W. van Leeuwen and G. van der Meulen]  Amyloid Precursor Protein and Ubiquitin-B in Alzheimer's and Down Patients Science. 1998 Jan 9;279(5348):242-7. PMID: 9422699 Fred W. van Leeuwen, Dominique P. V. de Kleijn, Helma H. van den Hurk, Andrea Neubauer, Marc A. F. Sonnemans, Jacqueline A. Sluijs, Soner Köycü, Ravindra D. J. Ramdjielal, Ahmad Salehi, Gerard J. M. Martens, Frank G. Grosveld, J. Peter H. Burbach, and Elly M. Hol Neuron 2006 July 6: 51 (1) 29-42 Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Read the coverage of this paper by: Science Scientist Stanford Medical Center Wall Street Journal BBC Alzforum Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of
Down syndromeJ Comp Neurol. 2009 Feb 1;512(4):453-66. PMID: 19034952 Belichenko PV, Kleschevnikov AM, Masliah E, Wu C, Takimoto-Kimura R, Salehi A, Mobley WC. Trends Neurosci. 2003 Feb;26(2):73-80. Traffic at the intersection of neurotrophic factor signaling and neurodegenerationSalehi A, Delcroix JD, Mobley WC. J Neurosci. 2009 May 6;29(18):5938-48. The "Down syndrome critical region" is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome Belichenko NP, Belichenko PV, Kleschevnikov AM, Salehi A, Reeves RH, Mobley WC. Citation Record
 Pharmacological Mechanisms in Alzheimer Ahmad Salehi, A Kleshevnikov, William c Mobley Citation Record
  Trafficking the NGF signal: implications for normal and degenerating neurons Delcroix JD, Valletta J, Wu C, Howe CL, Lai CF, Cooper JD, Belichenko PV, Salehi A, Mobley WC. Prog Brain Res. 2004;146:3-23. Citation Record  Alzheimer's Disease and Related Disorders Ahmad salehi, EJL Dubelaar, TA Ishunina, Dick F Swaab Edited by: K Iqbal, D F Swaab, B Winblad, HM Wisniewski Published by: 1999, John Wiley & Sons, Ltd, New York, USA ISBN: 0471986836 Citation Record
 Edited by: F.W. Van Leeuwen, Ahmad Salehi, R.J. Giger, A.J.G.D. Holtmaat, Joost Verhaagen Published by: 1998, Elsevier, Amsterdam, Netherlands  Connections, Cognition and Alzheimer's Disease DF Swaab, PJ Lucassen, JAP Van de NES, R Ravid, A Salehi Edited by: BT Hyman, C Duyckaertes, Y Christen Published by: 1997, Springer Verlag, Berlin, Germany ISBN: 3540622055 Citation Record Using mouse models to explore genotype-phenotype relationship
in Down syndromeMent Retard Dev Disabil Res Rev. 2007;13(3):207-14. PMID: 17910089 Salehi A, Faizi M, Belichenko PV, Mobley WC. J Comp Neurol. 2007 Oct 1;504(4):329-45. PMID: 19034952 Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring
genotype-phenotype relationshipsBelichenko PV, Kleschevnikov AM, Salehi A, Epstein CJ, Mobley WC Citation Record Synaptic structural abnormalities in the Ts65Dn mouse model of
Down SyndromeJ Comp Neurol. 2004 Dec 13;480(3):281-98. PMID: 15515178 Belichenko PV, Masliah E, Kleschevnikov AM, Villar AJ, Epstein CJ, Salehi A, Mobley WC Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10439-44. PMID: 11504920 Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J, Kilbridge JF, Carlson EJ, Epstein CJ, Mobley WC Alzheimer's disease and NGF signalingJ Neural Transm. 2004 Mar;111(3):323-45PMID: 14991458 Salehi A, Delcroix JD, Swaab DF Cells in human postmortem brain tissue slices remain alive for several weeks in culture FASEB J. 2002 Jan;16(1):54-60.PMID: 11772936 Verwer RW, Hermens WT, Dijkhuizen P, ter Brake O, Baker RE, Salehi A, Sluiter AA, Kok MJ, Muller LJ, Verhaagen J, Swaab DF Citation Record Molecular misreading: a new type of transcript mutation expressed during aging Neurobiol Aging. 2000 Nov-Dec;21(6):879-91. Review.PMID: 11124436 van Leeuwen FW, Fischer DF, Kamel D, Sluijs JA, Sonnemans MA, Benne R, Swaab DF, Salehi A, Hol EM Citation Record Sex- and age-related P75 neurotrophin receptor expression in the human Neuroendocrinology. 2000 Apr;71(4):243-51.PMID: 10773744 Ishunina TA, Salehi A, Swaab DF. Citation Record P75 neurotrophin receptor in the nucleus basalis of meynert in relation to age, sex, Exp Neurol. 2000 Jan;161(1):245-58. PMID: 10683291 Salehi A, Ocampo M, Verhaagen J, Swaab DF. Diminished neuronal metabolic activity J Neural Transm. 1999;106(9-10):955-86. Review.PMID: 10599878 Salehi A, Swaab DF Citation Record Activity of vasopressinergic neurones of the human supraoptic nucleus is J Neuroendocrinol. 1999 Apr;11(4):251-8.PMID: 10223278 Citation Record A sex difference and no effect of ApoE type on the amount of cytoskeletal alterations in the nucleus basalis of Meynert Neurobiol Aging. 1998 Nov-Dec;19(6):505-10.PMID: 10192208 Salehi A, Gonzalez Martinez V, Swaab DF Citation Record Activity of Hippocampal CA1 Neurons in Alzheimer's Disease is not Affected by the
Presence of Adjacent Neuritic PlaquesJ Alzheimers Dis. 1998 Dec;1(2):107-118. PMID: 12214007 Salehi A, Pool CW, Mulder M, Ravid R, Gonatas NK, Swaab DF Citation Record Reduced neuronal activity and reactivation in Prog Brain Res. 1998;117:343-77. Review.PMID: 9932420 Swaab DF, Lucassen PJ, Salehi A, Scherder EJ, van Someren EJ, Verwer RW Citation Record Neurotrophin receptors in Alzheimer's disease Prog Brain Res. 1998;117:71-89. PMID: 9932402 Salehi A, Verhaagen J, Swaab DF. Citation Record Aggravated decrease in the activity of nucleus basalis neurons in Alzheimer's disease is apolipoprotein E-type dependent Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11445-9.PMID: 9736756 Salehi A, Dubelaar EJ, Mulder M, Swaab DF Limited effect of neuritic plaques on neuronal density in the hippocampal CA1 area of Alzheimer Dis Assoc Disord. 1998 Jun;12(2):77-82.PMID: 9651135 Salehi A, Bakker JM, Mulder M, Swaab DF Citation Record Increased expression of the TIAR protein in the hippocampus of Neuroreport. 1998 May 11;9(7):1451-4.PMID: 9631446 Oleana VH, Salehi A, Swaab DF Citation Record The pathogenesis of Alzheimer disease: an alternative to the J Neuropathol Exp Neurol. 1997 Feb;56(2):216. PMID: 9034377 Swaab DF, Salehi A Citation Record Neuropeptides vasopressin (AVP), oxytocin (OXT) and corticotropin-releasing hormone (CRH) in the human hypothalamus: activity changes in aging, Alzheimer's disease and depression Aging (Milano). 1997;9(4 Suppl):48-50. PMID: 9358882 Lucassen PJ, Tilders FJ, Salehi A, Swaab DF Citation Record Early cytoskeletal changes as shown by Alz-50 are not accompanied by Brain Res. 1995 Apr 24;678(1-2):28-39.PMID: 7620896 Salehi A, Van de Nes JA, Hofman MA, Gonatas NK, Swaab DF Citation Record Activation of vasopressin neurons in aging and Alzheimer's disease J Neuroendocrinol. 1994 Dec;6(6):673-9.PMID: 7894470 Lucassen PJ, Salehi A, Pool CW, Gonatas NK, Swaab DF Citation Record Neuronal atrophy, not cell death, is the main hallmark of Alzheimer's disease Neurobiol Aging. 1994 May-Jun;15(3):369-71; discussion 379-80. PMID: 7936066 Swaab DF, Hofman MA, Lucassen PJ, Salehi A, Uylings HB Citation Record Salehi A, Lucassen PJ, Pool CW, Gonatas NK, Ravid R, Swaab DF View the Citation Metrics: |
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