Microtubule-associated proteins in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with granular cell layer dispersion.
Open accessAbstract
Background. Despite strong association between epilepsy and psychiatric comorbidities, biological substrates are unknown. We have previously reported decreased mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and increased in those with major depression. Microtubule associated proteins (MAPs) are essentially involved in dendritic and synaptic sprouting.Methods. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, and MTLE + interictal psychosis derived from epilepsy surgery and control necropsies were investigated for neuronal density, granular layer dispersion, and MAP2 and tau immunohistochemistry.Results. Altered MAP2 and tau expression in MTLE and decreased tau expression in MTLE with psychosis were found. Granular layer dispersion correlated inversely with verbal memory scores, and with MAP2 and tau expression in the entorhinal cortex. Patients taking fluoxetine showed increased neuronal density in the granular layer and those taking haloperidol decreased neuronal density in CA3 and subiculum.Conclusions. Our results indicate relations between MAPs, granular layer dispersion, and memory that have not been previously investigated. Differential MAPs expression in human MTLE hippocampi with and without psychiatric comorbidities suggests that psychopathological states in MTLE rely on differential morphological and possibly neurochemical backgrounds. This clinical study was approved by our institution’s Research Ethics Board (HC-FMRP no. 1270/2008) and is registered under the Brazilian National System of Information on Ethics in Human Research (SISNEP) no. 0423.0.004.000-07.
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Increased total and p-tau levels measured in surgically resected tissue from temporal lobe epilepsy patients are inversely correlated with cognitive scores.
“and increased total and p-tau levels measured in surgically resected tissue from TLE patients are inversely correlated with cognitive scores (Kandratavicius et al., 2013; Tai et al., 2016; Gourmaud et al., 2020).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Kandratavicius et al., 2013
Results §3.3 links greater tau immunoreactivity in CA2 of surgical MTLE specimens to below-average verbal scores, supporting the claim's direction for tau and cognition. Methods §2.3 specifies an antibody for total tau regardless of phosphorylation state; the paper does not report separate p-tau levels. The CA2 finding is a comparison between score groups, not a reported inverse correlation between tau levels and cognitive scores. (LLM, conf=0.88)
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- [1]Mathern GW Babb TL Pretorius JK Leite JP Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata Journal of Neuroscience 1995 15 5 3990 4004 2-s2.0-0029013993 7751960 PMC6578224
- [2]Babb TL Kupfer WR Pretorius JK Crandall PH Levesque MF Synaptic reorganization by mossy fibers in human epileptic fascia dentata Neuroscience 1991 42 2 351 363 2-s2.0-0025832553 1716744
- [3]Babb TL Brown WJ Pretorius J Davenport C Lieb JP Crandall PH Temporal lobe volumetric cell densities in temporal lobe epilepsy Epilepsia 1984 25 6 729 740 2-s2.0-0021747349 6510381
- [4]Isokawa M Remodeling dendritic spines of dentate granule cells in temporal lobe epilepsy patients and the rat pilocarpine model Epilepsia 2000 41 supplement 6 S14 S17 2-s2.0-0033816630 10999513
- [5]Scheibel ME Crandall PH Scheibel AB The hippocampal-dentate complex in temporal lobe epilepsy. A Golgi study Epilepsia 1974 15 1 55 80 2-s2.0-0016039943 4523024
- [6]Houser CR Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy Brain Research 1990 535 2 195 204 2-s2.0-0025203933 1705855
- [7]Silva AV Houzel J-C Croaro I Granular cell dispersion and bilamination: two distinct histopathological patterns in epileptic hippocampi? Epileptic Disorders 2007 9 4 438 442 2-s2.0-38349131941 18077231
- [8]Kandratavicius L Rosa-Neto P Monteiro MR Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis Hippocampus 2013 PMC4165311 23804486
- [9]Kandratavicius L Lopes-Aguiar C Bueno-Junior LS Romcy-Pereira RN Hallak JE Leite JP Psychiatric comorbidities in temporal lobe epilepsy: possible relationships between psychotic disorders and involvement of limbic circuits Revista Brasileira de Psiquiatria 2012 34 454 466 23429818
- [10]Kandratavicius L Ruggiero RN Hallak JE Garcia-Cairasco N Leite JP Pathophysiology of mood disorders in temporal lobe epilepsy Revista Brasileira de Psiquiatria 2012 34 S233 S259 23429849
- [11]Kandratavicius L Hallak JE Young LT Assirati JA Jr. Carlotti CG Jr. Leite JP Differential aberrant sprouting in temporal lobe epilepsy with psychiatric co-morbidities Psychiatry Research 2012 195 3 144 150 2-s2.0-84857647169 21741094
- [12]Pollard H khrestchatisky M Moreau J Ben-Ari Y Represa A Correlation between reactive sprouting and microtubule protein expression in epileptic hippocampus Neuroscience 1994 61 4 773 788 2-s2.0-0028120469 7838377
- [13]Yan XX Cai Y Shelton J Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like neuropathology in 3xTg-AD mice PLoS ONE 2012 7 e48782 PMC3498246 23155407
- [14]Tian F-F Zeng C Ma Y-F Potential roles of Cdk5/p35 and tau protein in hippocampal mossy fiber sprouting in the PTZ kindling model Clinical Laboratory 2010 56 3-4 127 136 2-s2.0-77951799645 20476644
- [15]Tucker RP The roles of microtubule-associated proteins in brain morphogenesis: a review Brain Research Reviews 1990 15 2 101 120 2-s2.0-0025201210 2282447
- [16]Dehmelt L Halpain S The MAP2/Tau family of microtubule-associated proteins Genome Biology 2005 6 1, article 204 2-s2.0-19744382953 PMC549057 15642108
- [17]Rosoklija G Toomayan G Ellis SP Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings Archives of General Psychiatry 2000 57 4 349 356 2-s2.0-0034115267 10768696
- [18]Cotter D Wilson S Roberts E Kerwin R Everall IP Increased dendritic MAP2 expression in the hippocampus in schizophrenia Schizophrenia Research 2000 41 2 313 323 2-s2.0-0033973980 10708340
- [19]Cotter D Kerwin R Doshi B Martin CS Everall IP Alterations in hippocampal non-phosphorylated MAP2 protein expression in schizophrenia Brain Research 1997 765 2 238 246 2-s2.0-0030982394 9313896
- [20]Arnold SE Cellular and molecular neuropathology of the parahippocampal region in schizophrenia Annals of the New York Academy of Sciences 2000 911 275 292 2-s2.0-0033914076 10911880
- [21]Arnold SE Lee VM-Y Gur RE Trojanowski JQ Abnormal expression of two microtubule-associated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia Proceedings of the National Academy of Sciences of the United States of America 1991 88 23 10850 10854 2-s2.0-0025885699 1961755 PMC53029
- [22]Gudmundsson P Skoog I Waern M The relationship between cerebrospinal fluid biomarkers and depression in elderly women The American Journal of Geriatric Psychiatry 2007 15 10 832 838 2-s2.0-38449105374 17911361
- [23]Law AJ Weickert CS Hyde TM Kleinman JE Harrison PJ Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines The American Journal of Psychiatry 2004 161 10 1848 1855 2-s2.0-2342508828 15465982
- [24]Blumcke I Zuschratter W Schewe JC Cellular pathology of hilar neurons in Ammon's horn sclerosis Journal of Comparative Neurology 1999 414 437 453 10531538
- [25]Dalmagro CL Velasco TR Bianchin MM Psychiatric comorbidity in refractory focal epilepsy: a study of 490 patients Epilepsy and Behavior 2012 25 593 597 23159384
- [26]Gaitatzis A Trimble MR Sander JW The psychiatric comorbidity of epilepsy Acta Neurologica Scandinavica 2004 110 4 207 220 2-s2.0-4644336111 15355484
- [27]Berg AT Identification of pharmacoresistant epilepsy Neurologic Clinics 2009 27 4 1003 1013 2-s2.0-70350060190 19853220 PMC2827183
- [28]Engel J Jr. Current concepts: surgery for seizures The New England Journal of Medicine 1996 334 10 647 652 2-s2.0-0030030960 8592530
- [29]Sachdev P Schizophrenia-like psychosis and epilepsy: the status of the association The American Journal of Psychiatry 1998 155 3 325 336 2-s2.0-0031917792 9501741
- [30]Beard AW Slater E The schizophrenic-like psychoses of epilepsy Proceedings of the Royal Society of Medicine 1962 55 311 316 2-s2.0-34447508856 13866149 PMC1896732
- [31]Anhê GF Torrão AS Nogueira TCA ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion Molecular and Cellular Endocrinology 2006 251 1-2 33 41 2-s2.0-33646561549 16597486
- [32]Ramirez DMO Andersson S Russell DW Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain Journal of Comparative Neurology 2008 507 5 1676 1693 2-s2.0-41549141257 18241055 PMC4015140
- [33]Jinwal UK Koren J III Borysov SI The Hsp90 cochaperone, FKBP51, increases tau stability and polymerizes microtubules Journal of Neuroscience 2010 30 2 591 599 2-s2.0-74949110831 20071522 PMC2830818
- [34]Hou Z Li Q He L Microtubule association of the neuronal p35 activator of Cdk5 Journal of Biological Chemistry 2007 282 26 18666 18670 2-s2.0-34547129366 17491008
- [35]Lorente de No R Studies on the structure of the cerebral cortex II. Continuation of study of the ammonic system Journal Für Psychologie Und Neurologie 1934 46 113 177
- [36]Abercrombie M Estimation of nuclear population from microtome sections Anatomical Record 1946 94 239 247 21015608
- [37]Mathern GW Adelson PD Cahan LD Leite JP Hippocampal neuron damage in human epilepsy: meyer’s hypothesis revisited Progress in Brain Research 2002 135 237 251 2-s2.0-0036456829 12143344
- [38]Mathern GW Pretorius JK Mendoza D Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients Annals of Neurology 1999 46 343 358 10482265
- [39]Mathern GW Mendoza D Lozada A Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy Neurology 1999 52 3 453 472 2-s2.0-0033015919 10025773
- [40]Mathern GW Pretorius JK Kornblum HI Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients Brain 1997 120 11 1937 1959 2-s2.0-0030786142 9397013
- [41]Mathern GW Babb TL Vickrey BG Melendez M Pretorius JK The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy Brain 1995 118 1 105 118 2-s2.0-0028939689 7894997
- [42]Peixoto-Santos JE Galvis-Alonso OY Velasco TR Increased metallothionein I/II expression in patients with temporal lobe epilepsy Plos ONE 2012 7 e44709 PMC3445538 23028585
- [43]Thom M Hippocampal sclerosis: progress since sommer Brain Pathology 2009 19 4 565 572 2-s2.0-69949142062 18761661 PMC8094764
- [44]Lurton D Sundstrom L Brana C Bloch B Rougier A Possible mechanisms inducing granule cell dispersion in humans with temporal lobe epilepsy Epilepsy Research 1997 26 2 351 361 2-s2.0-0030939201 9095397
- [45]Crespel A Coubes P Rousset M-C Immature-like astrocytes are associated with dentate granule cell migration in human temporal lobe epilepsy Neuroscience Letters 2002 330 1 114 118 2-s2.0-0037072538 12213646
- [46]Heck N Garwood J Loeffler J-P Larmet Y Faissner A Differential upregulation of extracellular matrix molecules associated with the appearance of granule cell dispersion and mossy fiber sprouting during epileptogenesis in a murine model of temporal lobe epilepsy Neuroscience 2004 129 2 309 324 2-s2.0-6344265574 15501589
- [47]Freiman TM Eismann-Schweimler J Frotscher M Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution Experimental Neurology 2011 229 2 332 338 2-s2.0-79956067926 21376037
- [48]Murphy BL Danzer SC Somatic translocation: a novel mechanism of granule cell dendritic dysmorphogenesis and dispersion Journal of Neuroscience 2011 31 8 2959 2964 2-s2.0-79951968961 21414917 PMC3115751
- [49]Hsu D The dentate gyrus as a filter or gate: a look back and a look ahead Progress in Brain Research 2007 163 601 613 2-s2.0-34548209899 17765740
- [50]Blümcke I Kistner I Clusmann H Towards a clinico-pathological classification of granule cell dispersion in human mesial temporal lobe epilepsies Acta Neuropathologica 2009 117 5 535 544 2-s2.0-64449087322 19277686
- [51]Pauli E Hildebrandt M Romstöck J Stefan H Blümcke I Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss Neurology 2006 67 8 1383 1389 2-s2.0-33750330128 17060564
- [52]Perera TD Coplan JD Lisanby SH Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates Journal of Neuroscience 2007 27 18 4894 4901 2-s2.0-34247856025 17475797 PMC6672102
- [53]Kodama M Fujioka T Duman RS Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat Biological Psychiatry 2004 56 8 570 580 2-s2.0-5044229846 15476686
- [54]Perera TD Dwork AJ Keegan KA Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult Nonhuman primates PLoS ONE 2011 6 4 2-s2.0-79954494320 e17600 PMC3078107 21525974
- [55]Moncrieff J Leo J A systematic review of the effects of antipsychotic drugs on brain volume Psychological Medicine 2010 40 9 1409 1422 2-s2.0-77957130430 20085668
- [56]Leite JP Babb TL Pretorius JK Kuhlman PA Yeoman KM Mathern GW Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal kainate in developing rats Epilepsy Research 1996 26 1 219 231 2-s2.0-0030550268 8985702
- [57]Ratzliff AH Santhakumar V Howard A Soltesz I Mossy cells in epilepsy: rigor mortis or vigor mortis? Trends in Neurosciences 2002 25 3 140 144 2-s2.0-0036498237 11852145
- [58]Yang C Wang G Wang H Liu Z Wang X Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress Behavioural Brain Research 2009 205 2 518 524 2-s2.0-70349782392 19683020
- [59]Yang H-J Li Y-F Zhang H-T Up-regulation of microtubule-associated protein 4 and drebrin A mRNA expression by antidepressants in rat hippocampus following chronic stress Neuroscience Letters 2003 351 3 206 208 2-s2.0-0242667907 14623141
- [60]Fournet V de Lavilleon G Schweitzer A Giros B Andrieux A Martres MP Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice Journal of Neurochemistry 2012 123 982 996 23013328
- [61]Schönknecht P Hempel A Hunt A Cerebrospinal fluid tau protein levels in schizophrenia European Archives of Psychiatry and Clinical Neuroscience 2003 253 2 100 102 2-s2.0-0141446378 12799749
- [62]Fatemi SH Earle JA McMenomy T Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression Molecular Psychiatry 2000 5 6 654 663 2-s2.0-0033646608 11126396
- [63]Eastwood SL Burnet PWJ Harrison PJ Altered synaptophysin expression as a marker of synaptic pathology in schizophrenia Neuroscience 1995 66 2 309 319 2-s2.0-0028965594 7477874
- [64]Chambers JS Thomas D Saland L Neve RL Perrone-Bizzozero NI Growth-associated protein 43 (GAP-43) and synaptophysin alterations in the dentate gyrus of patients with schizophrenia Progress in Neuro-Psychopharmacology and Biological Psychiatry 2005 29 2 283 290 2-s2.0-13444252739 15694236
- [65]Eastwood SL Harrison PJ Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons Schizophrenia Research 2005 73 2-3 159 172 2-s2.0-11844304923 15653259
- [66]Proper EA Oestreicher AB Jansen GH Immunohistochemical characterization of mossy fibre sprouting in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy Brain 2000 123 19 30 2-s2.0-0033628071 10611117
- [67]Gattaz WF Valente KD Raposo NRB Vincentiis S Talib LL Increased PLA2 activity in the hippocampus of patients with temporal lobe epilepsy and psychosis Journal of Psychiatric Research 2011 45 12 1617 1620 2-s2.0-80355133320 21813137
- [68]Mershin A Pavlopoulos E Fitch O Braden BC Nanopoulos DV Skoulakis EMC Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons Learning and Memory 2004 11 3 277 287 2-s2.0-2542590202 15169857 PMC419730
- [69]Pennanen L Wolfer DP Nitsch RM Götz J Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice Genes, Brain and Behavior 2006 5 5 369 379 2-s2.0-33745699023 16879631
- [70]Priel A Tuszynski JA Woolf NJ Neural cytoskeleton capabilities for learning and memory Journal of Biological Physics 2010 36 1 3 21 2-s2.0-73449132598 19669423 PMC2791806
- [71]Lauterbach EC Psychotropic drug effects on gene transcriptomics relevant to Parkinson’s disease Progress in Neuro-Psychopharmacology and Biological Psychiatry 2012 38 107 115 2-s2.0-84859930382 22507762
- [72]Lauterbach EC Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease Alzheimer Disease and Associated Disorders 2012 26 1 1 7 2-s2.0-84857784726 21399480
- [73]Gittins R Harrison PJ Neuronal density, size and shape in the human anterior cingulate cortex: a comparison of Nissl and NeuN staining Brain Research Bulletin 2004 63 2 155 160 2-s2.0-2342464932 15130705
- [74]Stan AD Ghose S Gao X-M Human postmortem tissue: what quality markers matter? Brain Research 2006 1123 1 1 11 2-s2.0-33751181235 17045977 PMC1995236
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Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms
Hwang, K., Vaknalli, R. N., Addo-Osafo, K., Vicente, M., & Vossel, K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903973 · Cited by 35 · see citing works
- Authors
- Kandratavicius, L., Monteiro, M. R., Hallak, J. E., Carlotti, C. G., Assirati, J. A., & Leite, J. P.
- Affiliations
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)
- Universidade de São Paulo (BR)
- Ribeirao Preto Medical School, Department of Surgery, USP, Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil
- Ribeirao Preto Medical School, Department of Neurosciences and Behavior, University of Sao Paulo (USP), Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-11
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC3771259
- OpenAlex
- W2033960115
- Cited by
- 31
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 5
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (05/56447-7, 150880/2012-0)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (05/56447-7, 150880/2012-0)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- mesial temporal lobe epilepsy, psychiatric comorbidity, microtubule-associated proteins, MAP2, tau protein, mossy fiber sprouting, psychosis, major depressive disorder, verbal memory, entorhinal cortex, hippocampus, neuronal density, fluoxetine, haloperidol, CA3, subiculum
- MeSH terms
- Adolescent, Cell Count, Child, Child, Preschool, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Male, Microtubule-Associated Proteins, Neurons, Comorbidity, tau Proteins
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