Skip to main content

Advertisement

SpringerLink
Log in

Wide distribution of CREM immunoreactivity in adult and fetal human brain, with an increased expression in dentate gyrus neurons of Alzheimer’s as compared to normal aging brains

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Human cyclic AMP response modulator proteins (CREMs) are encoded by the CREM gene, which generates 30 or more different CREM protein isoforms. They are members of the leucine zipper protein superfamily of nuclear transcription factors. CREM proteins are known to be implicated in a plethora of important cellular processes within the CNS. Amazingly, little is known about their cellular and regional distribution in the brain, however. Therefore, we studied by means of immunohistochemistry and Western blotting the expression patterns of CREM in developing and adult human brain, as well as in brains of Alzheimer’s disease patients. CREM immunoreactivity was found to be widely but unevenly distributed in the adult human brain. Its localization was confined to neurons. In immature human brains, CREM multiple neuroblasts and radial glia cells expressed CREM. In Alzheimer’s brain, we found an increased cellular expression of CREM in dentate gyrus neurons as compared to controls. We discuss our results with regard to the putative roles of CREM in brain development and in cognition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

Aβ:

Beta amyloid

AD:

Alzheimer’s disease

Aka:

Also known as

APP:

Amyloid precursor protein

ATF:

CREM/activating transcription factor

BA:

Brodmann area

cAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

CRE:

cAMP response element

CREB:

cAMP response element-binding protein

CREM:

cAMP response element modulator

Da:

Dalton

DG:

Dentate gyrus

EDTA:

Ethylene diamine tetraacetic acid

EGTA:

Ethylene glycol tetraacetic acid

ICER:

Inducible cAMP early repressor

IgG:

Immunoglobulin G

LCD:

Leucine-charged residue-rich domains

SDS:

Sodium dodecyl sulfate

bZIP:

Leucine zipper (protein superfamily)

References

  • Aguado F, Díaz-Ruiz C, Parlato R, Martínez A, Carmona MA, Bleckmann S, Ureña JM, Burgaya F, del Río JA, Schütz G, Soriano E (2009) The CREB/CREM transcription factors negatively regulate early synaptogenesis and spontaneous network activity. J Neurosci 29:328–333

    Article  PubMed  CAS  Google Scholar 

  • Ahlmann M, Varga G, Sturm K, Lippe R, Benedyk K, Viemann D, Scholzen T, Ehrchen J, Müller FU, Seidl M, Matus M, Tsokos GC, Roth J, Tenbrock K (2009) The cyclic AMP response element modulator alpha suppresses CD86 expression and APC function. J Immunol 182:4167–4174

    Article  PubMed  CAS  Google Scholar 

  • Arendt T (2005) Alzheimer’s disease as a disorder of dynamic brain self-organization. Prog Brain Res 147:355–378

    Article  PubMed  CAS  Google Scholar 

  • Avramopoulos D, Wang R, Valle D, Fallin MD, Bassett SS (2007) A novel gene derived from a segmental duplication shows perturbed expression in Alzheimer’s disease. Neurogenetics 8:111–120

    Article  PubMed  CAS  Google Scholar 

  • Barcellos LF, May SL, Ramsay PP, Quach HL, Lane JA, Nititham J, Noble JA, Taylor KE, Quach DL, Chung SA, Kelly JA, Moser KL, Behrens TW, Seldin MF, Thomson G, Harley JB, Gaffney PM, Criswell LA (2009) High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions. PLoS Genet 5:e1000696

    Article  PubMed  Google Scholar 

  • Behr R, Weinbauer GF (2000) CREM activator and repressor isoforms in human testis: sequence variations and inaccurate splicing during impaired spermatogenesis. Mol Hum Reprod 6:967–972

    Article  PubMed  CAS  Google Scholar 

  • Bernstein HG, Schön E, Ansorge S, Röse I, Dorn A (1987) Immunolocalization of dipeptidyl aminopeptidase (DAP IV) in the developing human brain. Int J Dev Neurosci 5:237–242

    Article  PubMed  CAS  Google Scholar 

  • Bernstein HG, Grecksch G, Becker A, Höllt V, Bogerts B (1999a) Cellular changes in rat brain areas associated with neonatal hippocampal damage. NeuroReport 10:2307–2311

    Article  PubMed  CAS  Google Scholar 

  • Bernstein HG, Baumann B, Danos P, Diekmann S, Bogerts B, Gundelfinger ED, Braunewell KH (1999b) Regional and cellular distribution of neural visinin-like protein immunoreactivities (VILIP-1 and VILIP-3) in human brain. J Neurocytol 28:655–662

    Article  PubMed  CAS  Google Scholar 

  • Bernstein HG, Smalla KH, Dürrschmidt D, Keilhoff G, Dobrowolny H, Steiner J, Schmitt A, Kreutz MR, Bogerts B (2012a) Increased density of prohibitin-immunoreactive oligodendrocytes in the dorsolateral prefrontal white matter of subjects with schizophrenia suggests extraneuronal roles for the protein in the disease. Neuromolecular Med 14:270–280

    Article  PubMed  CAS  Google Scholar 

  • Bernstein HG, Stich C, Jäger K, Dobrowolny H, Wick M, Steiner J, Veh R, Bogerts B, Laube G (2012b) Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders. Neuropharmacology 62:237–246

    Article  PubMed  CAS  Google Scholar 

  • Blöcher S, Fink L, Bohle RM, Bergmann M, Steger K (2005) CREM activator and repressor isoform expression in human male germ cells. Int J Androl 28:215–223

    Article  PubMed  Google Scholar 

  • Borsook D, Smirnova O, Behar O, Lewis S, Kobierski LA (1999) PhosphoCREB and CREM/ICER: positive and negative regulation of proenkephalin gene expression in the paraventricular nucleus of the hypothalamus. J Mol Neurosci 12:35–51

    Article  PubMed  CAS  Google Scholar 

  • Chiappini F, Ramadoss P, Vella KR, Cunha LL, Ye FD, Stuart RC, Nillni EA, Hollenberg AN (2013) Family members CREB and CREM control thyrotropin-releasing hormone (TRH) expression in the hypothalamus. Mol Cell Endocrinol 365:84–94

    Article  PubMed  CAS  Google Scholar 

  • Cortés-Mendoza J, Díaz de León-Guerrero S, Pedraza-Alva G, Pérez-Martínez L (2013) Shaping synaptic plasticity: the role of activity-mediated epigenetic regulation on gene transcription. Int J Dev Neurosci 31:359–369

    Article  PubMed  Google Scholar 

  • Crisafulli C, Chiesa A, Han C, Lee SJ, Shim DS, Balzarro B, Andrisano C, Sidoti A, Patkar AA, Pae CU, Serretti A (2012) Possible influence of CREB1, CREBBP and CREM variants on diagnosis and treatment outcome in patients with schizophrenia. Neurosci Lett 508:37–41

    Article  PubMed  CAS  Google Scholar 

  • De Felice FG, Wasilewska-Sampaio AP, Barbosa AC, Gomes FC, Klein WL, Ferreira ST (2007) Cyclic AMP enhancers and Abeta oligomerization blockers as potential therapeutic agents in Alzheimer’s disease. Curr Alzheimer Res 4:263–271

    Article  PubMed  Google Scholar 

  • Della Fazia MA, Servillo G, Sassone-Corsi P (1997) Cyclic AMP signalling and cellular proliferation: regulation of CREB and CREM. FEBS Lett 410:22–24

    Article  PubMed  CAS  Google Scholar 

  • Díaz-Ruiz C, Parlato R, Aguado F, Ureña JM, Burgaya F, Martínez A, Carmona MA, Kreiner G, Bleckmann S, Del Río JA, Schütz G, Soriano E (2008) Regulation of neural migration by the CREB/CREM transcription factors and altered Dab1 levels in CREB/CREM mutants. Mol Cell Neurosci 39:519–528

    Article  PubMed  Google Scholar 

  • Domschke K, Kuhlenbäumer G, Schirmacher A, Lorenzi C, Armengol L, DiBella D, Gratacos M, Garritsen HS, Nöthen MM, Franke P, Sand P, Fritze J, Perez G, Maier W, Sibrowski W, Estivill X, Bellodi L, Ringelstein EB, Arolt V, Martin-Santos R, Catalano M, Stögbauer F, Deckert J (2003) Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder. Am J Med Genet B Neuropsychiatr Genet 117B:70–78

    Article  PubMed  CAS  Google Scholar 

  • Fenaroli A, Vujanac M, De Cesare D, Zimarino VA (2004) Small-scale survey identifies selective and quantitative nucleo-cytoplasmic shuttling of a subset of CREM transcription factors. Exp Cell Res 299:209–226

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald LR, Vaidya VA, Terwilliger RZ, Duman RS (1996) Electroconvulsive seizure increases the expression of CREM (cyclic AMP response element modulator) and ICER (inducible cyclic AMP early repressor) in rat brain. J Neurosci 66:429–432

    CAS  Google Scholar 

  • Foulkes NS, Schlotter F, Pévet P, Sassone-Corsi P (1993) Pituitary hormone FSH directs the CREM functional switch during spermatogenesis. Nature 362(6417):264–267

    Article  PubMed  CAS  Google Scholar 

  • Foulkes NS, Borjigin J, Snyder SH, Sassone-Corsi P (1996) Transcriptional control of circadian hormone synthesis via the CREM feedback loop. Proc Natl Acad Sci USA 93:14140–14145

    Article  PubMed  CAS  Google Scholar 

  • Giedraitis V, Kilander L, Degerman-Gunnarsson M, Sundelöf J, Axelsson T, Syvänen AC, Lannfelt L, Glaser A (2009) Genetic analysis of Alzheimer’s disease in the Uppsala Longitudinal Study of Adult Men. Dement Geriatr Cogn Disord 27:59–68

    Article  PubMed  Google Scholar 

  • Ginsberg SD, Elarova I, Ruben M, Tan F, Counts SE, Eberwine JH, Trojanowski JQ, Hemby SE, Mufson EJ, Che S (2004) Single-cell gene expression analysis: implications for neurodegenerative and neuropsychiatric disorders. Neurochem Res 29:1053–1064

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Villafuertes R, Torres B, Barrio J, Savignac M, Gabellini N, Rizzato F, Pintado B, Gutierrez-Adan A, Mellström B, Carafoli E, Naranjo JR (2005) Downstream regulatory element antagonist modulator regulates Ca2+ homeostasis and viability in cerebellar neurons. J Neurosci 25:10822–10830

    Article  PubMed  CAS  Google Scholar 

  • Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JS, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrièze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O’Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A (2006) A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. Am J Hum Genet 78:78–88

    Article  PubMed  CAS  Google Scholar 

  • Hamilton SP, Slager SL, Mayo D, Heiman GA, Klein DF, Hodge SE, Fyer AJ, Weissman MM, Knowles JA (2004) Investigation of polymorphisms in the CREM gene in panic disorder. Am J Med Genet B Neuropsychiatr Genet 126B:111–115

    Google Scholar 

  • Herdegen T, Leah JD (1998) Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 28:370–490

    Article  PubMed  CAS  Google Scholar 

  • Hummler E, Cole TJ, Blendy JA, Ganss R, Aguzzi A, Schmid W, Beermann F, Schütz G (1994) Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc Natl Acad Sci USA 91:5647–56451

    Article  PubMed  CAS  Google Scholar 

  • Kadar E, Aldavert-Vera L, Huguet G, Costa-Miserachs D, Morgado-Bernal I, Segura-Torres P (2011) Intracranial self-stimulation induces expression of learning and memory-related genes in rat amygdala. Genes Brain Behav 10:69–77

    Article  PubMed  CAS  Google Scholar 

  • Kim SH, Nairn AC, Cairns N, Lubec G (2001) Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer’s disease. J Neural Transm Suppl 61:263–272

    PubMed  Google Scholar 

  • Konopka D, Szklarczyk AW, Filipkowski RK, Trauzold A, Nowicka D, Hetman M, Kaczmarek L (1998) Plasticity- and neurodegeneration-linked cyclic-AMP responsive element modulator/inducible cyclic-AMP early repressor messenger RNA expression in the rat brain. Neuroscience 86:499–510

    Article  PubMed  CAS  Google Scholar 

  • Kwakowsky A, Herbison AE, Ábrahám IM (2012) The role of cAMP response element-binding protein in estrogen negative feedback control of gonadotropin-releasing hormone neurons. J Neurosci 32:11309–11337

    Article  PubMed  CAS  Google Scholar 

  • Ledo F, Carrión AM, Link WA, Mellström B, Naranjo JR (2000) DREAM-alphaCREM interaction via leucine-charged domains derepresses downstream regulatory element-dependent transcription. Mol Cell Biol 20:9120–9126

    Article  PubMed  CAS  Google Scholar 

  • Link WA, Ledo F, Torres B, Palczewska M, Madsen TM, Savignac M, Albar JP, Mellström B, Naranjo JR (2004) Day-night changes in downstream regulatory element antagonist modulator/potassium channel interacting protein activity contribute to circadian gene expression in pineal gland. J Neurosci 24:5346–5355

    Article  PubMed  CAS  Google Scholar 

  • Luzzati F, De Marchis S, Parlato R, Gribaudo S, Schütz G, Fasolo A, Peretto P (2011) New striatal neurons in a mouse model of progressive striatal degeneration are generated in both the subventricular zone and the striatal parenchyma. PLoS One 6:e25088

    Article  PubMed  CAS  Google Scholar 

  • Madsen HB, Navaratnarajah S, Farrugia J, Djouma E, Ehrlich M, Mantamadiotis T, Van Deursen J, Lawrence AJ (2012) CREB1 and CREB-binding protein in striatal medium spiny neurons regulate behavioural responses to psychostimulants. Psychopharmacology 219:699–713

    Article  PubMed  CAS  Google Scholar 

  • Maldonado R, Smadja C, Mazzucchelli C, Sassone-Corsi P (1999) Altered emotional and locomotor responses in mice deficient in the transcription factor CREM. Proc Natl Acad Sci USA 96:14094–14099

    Article  PubMed  CAS  Google Scholar 

  • Mantamadiotis T, Lemberger T, Bleckmann SC, Kern H, Kretz O, Martin VA, Tronche F, Kellendonk C, Gau D, Kapfhammer J (2002) Disruption of CREB function in brain leads to neurodegeneration. Nat Genet 31:47–54

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki IK, Yamakuni T, Hashimoto M, Haque AM, Shido O, Mimaki Y, Sashida Y, Ohizumi Y (2006) Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer’s disease model. Neurosci Lett 400:230–234

    Article  PubMed  CAS  Google Scholar 

  • Mellström B, Naranjo JR, Foulkes NS, Lafarga M, Sassone-Corsi P (1993) Transcriptional response to cAMP in brain: specific distribution and induction of CREM antagonists. Neuron 10:655–665

    Article  PubMed  Google Scholar 

  • Nagy Z, Esiri MM, Cato AM, Smith AD (1997) Cell cycle markers in the hippocampus in Alzheimer’s disease. Acta Neuropathol 94:6–15

    Article  PubMed  CAS  Google Scholar 

  • Naranjo JR, Mellström B, Carrion AM, Lucas JJ, Foulkes NS, Sassore-Corsi P (1997) Peripheral noxious stimulation induces CREM expression in dorsal horn: involvement of glutamate. Eur J Neurosci 9:2778–2793

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F (2005) The embryonic human brain: an atlas of developmental stages, 3rd edn. Wiley, New York

    Google Scholar 

  • Ohm TG (2007) The dentate gyrus in Alzheimer’s disease. Progr Brain Res 163:723–740

    Article  CAS  Google Scholar 

  • Rauen T, Hedrich CM, Tenbrock K, Tsokos GC (2013) cAMP responsive element modulator: a critical regulator of cytokine production. Trends Mol Med. doi:10.1016/j.molmed.2013.02.001

  • Scott Bitner R (2012) Cyclic AMP response element-binding protein (CREB) phosphorylation: a mechanistic marker in the development of memory enhancing Alzheimer’s disease therapeutics. Biochem Pharmacol 83:705–714

    Article  PubMed  CAS  Google Scholar 

  • Servillo G, Della Fazia MA, Sassone-Corsi P (1998) Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver. Genes Dev 12:3639–6943

    Article  PubMed  CAS  Google Scholar 

  • Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P, Scholz SW, Hernandez DG, Krüger R, Federoff M, Klein C, Goate A, Perlmutter J, Bonin M, Nalls MA, Illig T, Gieger C, Houlden H, Steffens M, Okun MS, Racette BA, Cookson MR, Foote KD, Fernandez HH, Traynor BJ, Schreiber S, Arepalli S, Zonozi R, Gwinn K, van der Brug M, Lopez G, Chanock SJ, Schatzkin A, Park Y, Hollenbeck A, Gao J, Huang X, Wood NW, Lorenz D, Deuschl G, Chen H, Riess O, Hardy JA, Singleton AB, Gasser T (2009) Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet 41:1308–1312

    Article  PubMed  Google Scholar 

  • Smalmeiser NR, Lugli G (2009) microRNA regulation of synaptic plasticity. Neuromolecular Med 11:133–140

    Article  Google Scholar 

  • Stehle JH, Foulkes NS, Molina CA, Simonneaux V, Pévet P, Sassone-Corsi P (1993) Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland. Nature 365(6444):314–320

    Article  PubMed  CAS  Google Scholar 

  • Thal DR, Holzer M, Rüb U, Waldmann G, Günzel S, Zedlick D, Schober R (2000) Alzheimer-related tau pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol 163:98–110

    Article  PubMed  CAS  Google Scholar 

  • Uyttersprot N, Miot F (1997) Dog CREM transcription factors: cloning, tissue distribution, and identification of new isoforms. Biochem Biophys Res Commun 237:74–78

    Article  PubMed  CAS  Google Scholar 

  • van Strien ME, van den Berge SA, Hol EM (2011) Migrating neuroblasts in the adult human brain: a stream reduced to a trickle. Cell Res 21:1523–1525

    Article  PubMed  Google Scholar 

  • Wang A, Bibb JA (2011) Is CREB the angry bird that releases memory in Alzheimer’s? Neuropsychopharmacology 36:2153–2154

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Jin W, Liu X, Fu H, Gong P, Xu J, Cui G, Ng Y, Ke K, Gao Z, Gao Y (2012) Cyclic AMP response element modulator-1 (CREM-1) involves in neuronal apoptosis after traumatic brain injury. J Mol Neurosci 47:357–367

    Article  PubMed  CAS  Google Scholar 

  • The Human Protein Atlas (Uppsala Universiteit). http://www.proteinatlas.org/

  • Yamamoto-Sasaki M, Ozawa H, Saito T, Rösler M, Riederer P (1999) Impaired phosphorylation of cyclic AMP response element binding protein in the hippocampus of dementia of the Alzheimer type. Brain Res 824:300–303

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci USA 102:4459–4464

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Han X, Blendy JA, Porter BE (2012) Decreased CREB levels suppress epilepsy. Neurobiol Dis 45:253–263

    Article  PubMed  CAS  Google Scholar 

  • Zubenko GS, Maher B, Hughes HB 3rd, Zubenko WN, Stiffler JS, Kaplan BB, Marazita ML (2003) Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet 123B(1):1–18

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The skillful technical work of Leona Bück, Ines Schellhase, Sandra Hartmann, Bianca Jerzykiewicz and Nadine Klappoth is highly appreciated.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Hans-Gert Bernstein, Bernhard Bogerts, Marina Zempeltzi, Johann Steiner & Henrik Dobrowolny

  2. Departments of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany

    Elmar Kirches & Christian Mawrin

  3. Department of Biochemistry and Molecular Biology, University of Greifswald, Greifswald, Germany

    Uwe Lendeckel

  4. Institute of Biochemistry and Cell Biology, Otto-von-Guericke-University, Magdeburg, Germany

    Gerburg Keilhoff

  5. Department of Pediatrics, RWTH Aachen, Aachen, Germany

    Klaus Tenbrock

  6. Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Vasileios C. Kyttaris

Authors
  1. Hans-Gert Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elmar Kirches
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernhard Bogerts
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Uwe Lendeckel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gerburg Keilhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marina Zempeltzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Johann Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Klaus Tenbrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Henrik Dobrowolny
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vasileios C. Kyttaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christian Mawrin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hans-Gert Bernstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernstein, HG., Kirches, E., Bogerts, B. et al. Wide distribution of CREM immunoreactivity in adult and fetal human brain, with an increased expression in dentate gyrus neurons of Alzheimer’s as compared to normal aging brains. Amino Acids 45, 1373–1383 (2013). https://doi.org/10.1007/s00726-013-1601-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-013-1601-2

Keywords

Search

Navigation