Alterations in dendritic length and branch and K+ -Cl - cotransporter 2 expression of the olfactory bulb in young APP/PS1 mice

CHEN Bo-Yu; JIANG Jin-Xiang; ZHANG Jia-Wei; YANG Li

doi:10.16098/j.issn.0529-1356.2023.02.001

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (2) : 127-133. DOI: 10.16098/j.issn.0529-1356.2023.02.001

Alterations in dendritic length and branch and K+ -Cl - cotransporter 2 expression of the olfactory bulb in young APP/PS1 mice

CHEN Bo-yu¹ JIANG Jin-xiang² ZHANG Jia-wei² YANG Li^1*

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Abstract

Objective To study the morphology of olfactory bulb(OB) neurons and the change of related proteins, and explore the causes of olfactory dysfuction in Alzheimer’s disease(AD). Methods Golgi-Cox staining technique was used to evaluate the morphological changes of neurons in the OB and anterior piriform cortex (aPC) of APP/PS1 AD model mice. The morphology of neurons was determined by Sholl analysis. Western blotting was used to evaluate the levels of protein expression. Results The results of Golgi-Cox showed that the dendrite length and branch number reduced significantly in the OB neurons of 3-5-month-old APP/PS1 mice, an age that the mice did not show the pathological characteristics and cognitive impairment of AD. Western blotting analysis showed that levels of potassium chloride cotransporter 2（KCC2）, a potassium chloride transporter crucial for neuronal morphology and synaptic function, decreased significantly in the OB of 3-5-month-old APP/PS1 mice. Conclusion Abnormal neuronal morphology and KCC2 signal might be the basis of early olfactory dysfunction in AD. Thus, maintaining normal KCC2 signal may be one of the keys to intervene the olfactory abnormalities in the early stage of AD.

Key words

Alzheimer’s disease / Olfactory bulb / Anterior piriform cortex / Potassium chloride cotransporter 2 / Western blotting / Mouse

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CHEN Bo-yu JIANG Jin-xiang ZHANG Jia-wei YANG Li. Alterations in dendritic length and branch and K+ -Cl - cotransporter 2 expression of the olfactory bulb in young APP/PS1 mice[J]. Acta Anatomica Sinica. 2023, 54(2): 127-133 https://doi.org/10.16098/j.issn.0529-1356.2023.02.001

References

［1］Chen M, Chen Y, Huo Q, et al. Enhancing GABAergic signaling ameliorates aberrantgamma oscillations of olfactory bulb in AD mouse models ［J］. Mol Neurodegener, 2021, 16(1):14.

［2］Swan GE, Carmelli D. Impaired olfaction predicts cognitive decline in nondementedolder adults ［J］. Neuroepidemiology, 2002, 21(2): 58-67.

［3］Zhang JW, Tabassum S, Jiang JX, et al. Optimized Golgi-Cox staining validated inthe hippocampus of spared nerve injury mouse model［J］. Front Neuroanat, 2020, 14: 585513.

［4］Gibb R, Kolb B. A method for vibratome sectioning of Golgi-Cox stained whole rat brain［J］. J Neurosci Methods, 1998, 79(1): 1-4.

［5］Zhou G, Lane G, Cooper SL, et al. Characterizing functional pathways of the humanolfactory system ［J］. Elife, 2019, 8：e47177.

［6］Kumar A, Schiff O, Barkai E, et al. NMDA spikes mediate amplification of inputs inthe rat piriform cortex ［J］. Elife, 2018, 7：e38446.

［7］Courtiol E, Buonviso N, Litaudon P. Odorant features differentially modulatebeta/gamma oscillatory patterns in anterior versus posterior piriform cortex［J］Neuroscience,2019, 409: 26-34.

［8］Meng Y, Liu BF, Cai Q, et al. Influence of olfactory bulb removal on the proliferation anddifferentiation of new neurons originated from the subventricular zone of adult rat brain ［J］. Acta Anatomica Sinica, 2007, 38(6): 631-635.（in Chinese）

孟艳, 刘丙方, 蔡青, 等. 嗅球切除对成年大鼠侧脑室外侧壁新生细胞增殖和分化的影响［J］. 解剖学报, 2007, 38(6): 631-635.

［9］Kaila K, Price TJ, Payne JA, et al. Cation-chloride cotransporters in neuronaldevelopment, plasticity and disease ［J］. Nat Rev Neurosci, 2014, 15(10): 637-654.

［10］Godde K, Gschwend O, Puchkov D, et al. Disruption of KCC2-dependent inhibition ofolfactory bulb output neurons suggests its importance in odour discrimination ［J］. Nat Commun,2016, 7: 12043.

［11］Li H, Khirug S, Cai C, et al. KCC2 interacts with the dendritic cytoskeleton to promote spinedevelopment ［J］. Neuron, 2007, 56(6): 1019-1033.

［12］Blaesse P, Schmidt T. K-Cl cotransporter KCC2-a moonlighting protein in excitatoryand inhibitory synapse development and function ［J］. Pflugers Arch, 2015, 467(4): 615-624.

［13］Adlard PA, Vickers JC. Morphologically distinct plaque types differentially affectdendritic structure and organisation in the early and late stages of Alzheimer ’s disease ［J］. Acta Neuropathol, 2002, 103(4): 377-383.

［14］Spruston N. Pyramidal neurons: dendritic structure and synaptic integration ［J］. Nat RevNeurosci, 2008, 9(3): 206-221.

［15］Tsai J, Grutzendler J, Duff K, et al. Fibrillar amyloid deposition leads to local synapticabnormalities and breakage of neuronal branches ［J］. Nat Neurosci, 2004, 7(11): 1181-1183.

［16］Tan J, Luo MM. Olfactory bulb processing of olfactory information ［J］. Journal of Biophysics, 2010, 26(3): 194-208. （in Chinese）

谭洁, 罗敏敏. 嗅球对嗅觉信息的处理［J］. 生物物理学报, 2010,26(3):194-208.

［17］Yao ZG, Hua F, Zhang HZ, et al. Olfactory dysfunction in the APP/PS1 transgenic mousemodel of Alzheimer’s disease: morphological evaluations from the nose to the brain［J］.Neuropathology, 2017, 37(6): 485-494.

［18］Yaffe K, Freimer D, Chen H, et al. Olfaction and risk of dementia in a biracial cohort ofolder adults ［J］. Neurology, 2017, 88(5): 456-462.

［19］Ben-Ari Y. Excitatory actions of gaba during development: the nature of the nurture ［J］. NatRev Neurosci, 2002, 3(9): 728-739.

［20］Moore YE, Conway LC, Wobst HJ, et al. Developmental regulation of KCC2 phosphorylation has long-term impacts on cognitive function ［J］. Front Mol Neurosci, 2019,12: 173.

［21］Attems J, Walker L, Jellinger KA. Olfactory bulb involvement in neurodegenerativediseases ［J］. Acta Neuropathol, 2014, 127(4): 459-475.

［22］Braak H, Tredici KD. The pathological process underlying Alzheimer’s disease inindividuals under thirty ［J］. Acta Neuropathol, 2011, 121(2): 171-181.

［23］Wilson RS, Schneider JA, Arnold SE, et al. Olfactory identification and incidence of mild cognitive impairment in older age ［J］. Arch Gen Psychiatry, 2007, 64(7): 802-808.

［24］Albers MW, Gilmore GC, Kaye J, et al. At the interface of sensory and motordysfunctions and Alzheimer’s disease ［J］. Alzheimers Dement, 2015, 11(1): 70- 98.

［25］Roalf DR, Moberg MJ, Turetsky BI, et al. A quantitative meta-analysis of olfactorydysfunction in mild cognitive impairment ［J］. J Neurol Neurosurg Psychiatry, 2017, 88(3): 226-232.