Age‑dependent concomitant changes in synaptic function and GABAergic pathway in the APP/PS1 mouse model

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Acta Neurobiologiae Experimentalis

Nencki Institute of Experimental Biology

Polish Neuroscience Society

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VOLUME 76 , ISSUE 4 (December 2016) > List of articles

Advertisement Age‑dependent concomitant changes in synaptic function and GABAergic pathway in the APP/PS1 mouse model

Tutu Oyelami / An De Bondt / Ilse Van den Wyngaert / Kirsten Van Hoorde / Luc Hoskens / Hamdy Shaban / John A. Kemp / Wilhelmus H. Drinkenburg *

Keywords : GABAergic, glutamatergic, seizures, Alzheimer’s disease, APP/PS1, long‑term potentiation, expression profile

Citation Information : Acta Neurobiologiae Experimentalis. Volume 76, Issue 4, Pages 282-293, DOI: https://doi.org/10.21307/ane-2017-027

License : (CC BY 4.0)

Published Online: 31-July-2017

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ABSTRACT

Synaptic dysfunction is a well‑documented manifestation in animal models of Alzheimer’s disease pathology. In this context, numerous studies have documented reduction in the functionality of synapses in various models. In addition, recent research has shed more light on increased excitability and its link to seizures and seizure‑like activities in AD patients as well as in mouse models. These reports of hyperexcitability contradict the observed reduction in synaptic function and have been suggested to be as a result of the interplay between inhibitory and excitatory neuronal mechanism. The present study therefore investigates functional deficiency in the inhibitory system as complementary to the identified alterations in the glutamate excitatory pathway in AD. Since synaptic function deficit in AD is typically linked to progression/pathology of the disease, it is important to determine whether the deficits in the GABAergic system are functional and can be directly linked to the pattern of the disruption documented in the glutamate system. To build on previous research in this field, experiments were designed to determine if previously documented synaptic dysfunction in AD models is concomitantly observed with excitation/inhibition imbalance as suggested by observation of seizure and seizure‑like pathology in such models. We report changes in synaptic function in aged APPPS1 mice not observable in the younger cohort. These changes in synaptic function are furthermore accompanied by alteration in the GABAergic neurotransmission. Thus, age‑dependent alteration in the inhibitory/ excitatory balance might underpin the symptomatic changes observed with the progression of Alzheimer’s disease pathology including sleep disturbance and epileptic events.

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REFERENCES

  1. Alzheimer’s‑Association (2015) Alzheimer’s disease facts and figures. Alzheimer Dement 11(3): 332–384.
  2. Amatniek JC, Hauser WA, DelCastillo‑Castaneda C, Jacobs DM, Marder K, Bell K, Albert M, Brandt J, Stern Y (2006) Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia 47(5): 867–872.
  3. Andrews‑Zwilling Y, Bien‑Ly N, Xu Q, Li G, Bernardo A, Yoon SY, Zwilling D, Yan TX, Chen L, Huang Y (2010) Apolipoprotein E4 causes age‑ and Tau‑dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J Neurosci 30(41): 13707–13717.
  4. Bergado JA, Almaguer W (2002) Aging and synaptic plasticity: a review. Neural Plast 9(4): 217–232.
  5. Bliim N, Leshchyns’ka I, Sytnyk V, Janitz M (2016) Transcriptional regulation of long‑term potentiation neurogenetics. Neurogenetics 17(4): 201–210. doi: 10.1007/s10048‑016‑0489‑x.
    [CROSSREF]
  6. Blumcke I, Beck H, Scheffler B, Hof PR, Morrison JH, Wolf HK, Schramm J, Elger CE, Wiestler OD (1996) Altered distribution of the alpha‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazole propionate receptor subunit GluR2(4) and the N‑methyl‑D‑aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy. Acta Neuropathol 92(6): 576–587.
  7. Borden LA (1996) GABA transporter heterogeneity: pharmacology and cellular localization. Neurochem Int 29(4): 335–356.
  8. Chebib M, Johnston GA (1999) The ‘ABC’ of GABA receptors: a brief review. Clin Exp Pharmacol Physiol 26(11): 937–940.
  9. Cloyd J, Hauser W, Towne A, Ramsay R, Mattson R, Gilliam F, Walczak T (2006) Epidemiological and medical aspects of epilepsy in the elderly. Epilepsy Res 68 Suppl 1: S39–S48.
  10. Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, Watson SJ, Meng F (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res 33(20): e175.
  11. Davies P, Katzman R, Terry RD (1980) Reduced somatostatin‑like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa. Nature 288(5788): 279–280.
  12. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27: 457–464. doi: 10.1002/ana.410270502.
  13. Durkin MM, Smith KE, Borden LA, Weinshank RL, Branchek TA, Gustafson EL (1995) Localization of messenger RNAs encoding three GABA transporters in rat brain: an in situ hybridization study. Brain Res Mol Brain Res 33(1): 7–21.
  14. Fitzjohn SM, Kuenzi F, Morton RA, Rosahl TW, Lewis H, Smith D, Seabrook GR, Collingridge GL (2010) A study of long‑term potentiation in transgenic mice over‑expressing mutant forms of both amyloid precursor protein and presenilin‑1. Mol Brain 3(1): 21.
  15. Freund TF, Katona I (2007) Perisomatic inhibition. Neuron 56(1): 33–42.
  16. Gengler S, Hamilton A, Holscher C (2010) Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer’s disease is impaired in old but not young mice. PLoS One 5(3): e9764.
  17. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JYH, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10): R80.
  18. Grady CL, Furey ML, Pietrini P, Horwitz B, Rapoport SI (2001) Altered brain functional connectivity and impaired short‑term memory in Alzheimer’s disease. Brain 124: 739–756.
  19. Harris JA, Devidze N, Verret L, Ho K, Halabisky B, Thwin MT, Kim D, Hamto P, Lo I, Yu GQ, Palop JJ, Masliah E, Mucke L (2010) Transsynaptic progression of amyloid‑beta‑induced neuronal dysfunction within the entorhinal‑hippocampal network. Neuron 68(3): 428–441.
  20. Hauser WA, Morris ML, Heston LL, Anderson VE (1986) Seizures and myoclonus in patients with Alzheimer’s disease. Neurology 36(9): 1226–1230.
  21. Hazra A, Corbett BF, You JC, Aschmies S, Zhao L, Li K, Lepore AC, Marsh ED, Chin J (2016) Corticothalamic network dysfunction and behavioral deficits in a mouse model of Alzheimer’s disease. Neurobiol Aging 44: 96–107.
  22. Hazra A, Gu F, Aulakh A, Berridge C, Eriksen JL, Ziburkus J (2013) Inhibitory neuron and hippocampal circuit dysfunction in an aged mouse model of Alzheimer’s disease. PLoS One 8(5): e64318.
  23. Howell O, Atack JR, Dewar D, McKernan RM, Sur C (2000) Density and pharmacology of alpha5 subunit‑containing GABA(A) receptors are preserved in hippocampus of Alzheimer’s disease patients. Neuroscience 98(4): 669–675.
  24. Hoxha E, Boda E, Montarolo F, Parolisi R, Tempia F (2012) Excitability and synaptic alterations in the cerebellum of APP/PS1 mice. PLoS One 7(4): e34726.
  25. Huang H, Nie S, Cao M, Marshall C, Gao J, Xiao N, Hu G, Xiao M (2016) Characterization of AD‑like phenotype in aged APPSwe/PS1dE9 mice. Age (Dordr) 38(4): 303–322. doi: 10.1007/s11357‑016‑9929‑7.
  26. Irizarry MC, Jin S, He F, Emond JA, Raman R, Thomas RG, Sano M, Quinn JF, Tariot PN, Galasko DR, Ishihara LS, Weil JG, Aisen PS (2012) Incidence of new‑onset seizures in mild to moderate Alzheimer disease. Arch Neurol 69(3): 368–372.
  27. Irizarry RA, Hobbs B, Collin F, Beazer‑Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4(2): 249–264.
  28. Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR (2001) Co‑expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6): 157–165.
  29. Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH, Bae JY, Kim T, Lee J, Chun H, Park HJ, Lee da Y, Hong J, Kim HY, Oh SJ, Park SJ, Lee H, Yoon BE,
    Kim Y, Jeong Y, Shim I, Bae YC, Cho J, Kowall NW, Ryu H, Hwang E, Kim D, Lee CJ (2014) GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease. Nat Med 20(8): 886–896.
  30. Johnston GA (2013) Advantages of an antagonist: bicuculline and other GABA antagonists. Br J Pharmacol 169(2): 328–336.
  31. Karnup S, Stelzer A (1999) Temporal overlap of excitatory and inhibitory afferent input in guinea‑pig CA1 pyramidal cells. J Physiol 516: 485–504. doi: 10.1111/j.1469‑7793.1999.0485v.x.
  32. Kersante F, Rowley SC, Pavlov I, Gutierrez‑Mecinas M, Semyanov A, Reul JM, Walker MC, Linthorst AC (2013) A functional role for both ‑aminobutyric acid (GABA) transporter‑1 and GABA transporter‑3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus. J Physiol 591(10): 2429–2441.
  33. King GL, Knox JJ, Dingledine R (1985) Reduction of inhibition by a benzodiazepine antagonist, Ro15‑1788, in the rat hippocampal slice. Neuroscience 15: 371–378.
  34. Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ (2011) Soluble Abeta oligomers inhibit long‑term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B‑containing NMDA receptors. J Neurosci 31(18): 6627–6638.
  35. Limon A, Reyes‑Ruiz JM, Miledi R (2012) Loss of functional GABA(A) receptors in the Alzheimer diseased brain. Proc Natl Acad Sci U S A 109(25): 10071–10076.
  36. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol 155(3): 853–862.
  37. Lynch MA (2004) Long‑term potentiation and memory. Physiol Rev 84(1): 87–136.
  38. Malenka RC, Nicoll RA (1999) Long‑term potentiation‑‑a decade of progress?. Science 285(5435): 1870–1874.
  39. Mann DM, Pickering‑Brown SM, Takeuchi A, Iwatsubo T (2001) Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin‑1‑linked Alzheimer’s disease. Am J Pathol 158(6): 2165–2175.
  40. Meilandt WJ, Yu GQ, Chin J, Roberson ED, Palop JJ, Wu T, Scearce‑Levie K, Mucke L (2008) Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer’s disease. J Neurosci 28(19): 5007–5017.
  41. Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fulop L, Penke B, Zilberter Y, Harkany T, Pitkanen A, Tanila H (2009) Amyloid beta‑induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 29(11): 3453–3462.
  42. Moehlmann T, Winkler E, Xia X, Edbauer D, Murrell J, Capell A, Kaether C, Zheng H, Ghetti B, Haass C, Steiner H (2002) Presenilin‑1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci U S A 99(12): 8025–8030.
  43. Mu Y, Gage FH (2011) Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener 6: 85. doi: 10.1186/1750‑1326‑‑6‑85.
  44. Nankai M, Fage D, Carter C (1995) NMDA receptor subtype selectivity: eliprodil, polyamine spider toxins, dextromethorphan, and desipramine selectively block NMDA‑evoked striatal acetylcholine but not spermidine release. J Neurochem 64(5): 2043–2048.
  45. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien‑Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L (2007) Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron 55(5): 697–711.
  46. Palop JJ, Mucke L (2009) Synaptic depression and aberrant excitatory network activity in Alzheimer’s disease: two faces of the same coin?. Neuromolecular Med 12(1): 48–55.
  47. Palop JJ, Mucke L (2010) Amyloid‑beta‑induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci 13(7): 812–818.
  48. Radde R, Bolmont T, Kaeser SA, Coomaraswamy J, Lindau D, Stoltze L, Calhoun ME, Jaggi F, Wolburg H, Gengler S, Haass C, Ghetti B, Czech C, Holscher C, Mathews PM, Jucker M (2006) Abeta42‑driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep 7(9): 940–946.
  49. Ramos B, Baglietto‑Vargas D, del Rio JC, Moreno‑Gonzalez I, Santa‑Maria C, Jimenez S, Caballero C, Lopez‑Tellez JF, Khan ZU, Ruano D, Gutierrez A, Vitorica J (2006) Early neuropathology of somatostatin/NPY GABAergic cells in the hippocampus of a PS1xAPP transgenic model of Alzheimer’s disease. Neurobiol Aging 27(11): 1658–1672.
  50. Rossor MN, Fox NC, Beck J, Campbell TC, Collinge J (1996) Incomplete penetrance of familial Alzheimer’s disease in a pedigree with a novel presenilin‑1 gene mutation. Lancet 347(9014): 1560. Schwab C, Yu S, Wong W, McGeer EG, McGeer PL (2013) GAD65, GAD67, and GABAT immunostaining in human brain and apparent GAD65 loss in Alzheimer’s disease. J Alzheimers Dis 33(4): 1073–1088.
  51. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL (2007) Natural oligomers of the Alzheimer amyloid‑beta protein induce reversible synapse loss by modulating an NMDA‑type glutamate receptor‑dependent signaling pathway. J Neurosci 27(11): 2866–2875.
  52. Sheng M, Sabatini BL, Südhof TC (2012) Synapses and Alzheimer’s disease. Cold Spring Harb Perspect Biol 4(5): a005777.
  53. Shors TJ, Matzel LD (1997) Long‑term potentiation: what’s learning got to do with it?. Behav Brain Sci 20(4): 597–614.
  54. Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3(1): 1–25.
  55. Takahashi H, Brasnjevic I, Rutten BP, Van Der Kolk N, Perl DP, Bouras C, Steinbusch HW, Schmitz C, Hof PR, Dickstein DL (2010) Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer’s disease. Brain Struct Funct 214(2–3): 145–160.
  56. Tong LM, Djukic B, Arnold C, Gillespie AK, Yoon SY, Wang MM, Zhang O, Knoferle J, Rubenstein JL, Alvarez‑Buylla A, Huang Y (2014) Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock‑in mice without or with Abeta accumulation. J Neurosci 34(29): 9506–9515.
  57. Trinchese F, Liu S, Battaglia F, Walter S, Mathews PM, Arancio O (2004) Progressive age‑related development of Alzheimer‑like pathology in APP/PS1 mice. Ann Neurol 55(6): 801–814.
  58. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ (2012) Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149(3): 708–721.
  59. Viana da Silva S, Haberl MG, Zhang P, Bethge P, Lemos C, Gonçalves N, Gorlewicz A, Malezieux M, Gonçalves FQ, Grosjean N, Blanchet C, Frick A, Nägerl UV, Cunha RA, Mulle C (2016) Early synaptic deficits in the APP/ PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors. Nat Commun 7: 11915.
  60. Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014) Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5: 88.
  61. Winblad B, Poritis N (1999) Memantine in severe dementia: results of the 9M‑Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 14(2): 135–146.
  62. Xie XH, Tietz EI (1991) Chronic benzodiazepine treatment of rats induces reduction of paired‑pulse inhibition in CA1 region of in vitro hippocampus. Brain Res 561: 69–76.
  63. Xiong H, Gendelman HE, Zhang J, Xia J (2013) Techniques for extracellular recordings, In: Current Laboratory Methods in Neuroscience Research (Xiong H, Gendelman HE, Eds.). Springer New York, USA, p. 325–345.
  64. Yoshiike Y, Kimura T, Yamashita S, Furudate H, Mizoroki T, Murayama M and Takashima A (2008) GABA(A) receptor‑mediated acceleration of aging‑associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin. PLoS One 3(8): e3029.
  65. Zhang W, Hao J, Liu R, Zhang Z, Lei G, Su C, Miao J, Li Z (2011) Soluble Aβ levels correlate with cognitive deficits in the 12‑month‑old APPswe/ PS1dE9 mouse model of Alzheimer’s disease. Behav Brain Res 222(2): 342–350.

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