Abstract
Specific neuronal spatial distributional patterns have previously been correlated with increasing severity of HIV-associated dementia (HAD). As astrocytes are also a putative site of neurotoxicity, we investigated the spatial relationships of astrocytes with pyramidal and interneurons in the superior frontal gyrus from 29 patients who died from acquired immunodeficiency syndrome. Frontal cortical brain tissue was taken from diseased HIV patients who had been assessed for the presence and severity of HAD using the Memorial Sloan-Kettering Scale. No correlation was found between neuronal density and severity of dementia. However, the pattern of astrocytes became more clustered as dementia progressed. Bivariate spatial pattern analysis of neuronal populations with astrocytes revealed that, with increasing dementia severity, astrocytes and large pyramidal neurons increasingly “repelled” each other, while astrocytes and interneurons evidenced increasing “attraction.” This implies that astrocytes may be more likely to be situated in the vicinity of surviving interneurons but less likely to be situated near surviving large pyramidal neurons in the setting of progressing HAD.
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References
Araque A, Navarrete M (2010) Glial cells in neuronal network function. Philos Trans R Soc Lond B Biol Sci 365:2375–2381. doi:10.1098/rstb.2009.0313
Asare E, Dunn G, Glass J, McArthur J, Luthert P, Lantos P, Everall I (1996) Neuronal pattern correlates with the severity of human immunodeficiency virus-associated dementia complex. Usefulness of spatial pattern analysis in clinicopathological studies. Am J Pathol 148:31–38
Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNF[alpha]: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710
Borjabad A, Brooks AI, Volsky DJ (2009) Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders. J NeuroImmune Pharm 5:44–62. doi:10.1007/s11481-009-9167-1
DeFelipe J (1997) Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28K, parvalbumin and calretinin in the neocortex. J Chem Neuroanat 14:1–19. doi:S0891061897100138
Deshpande M, Zheng J, Borgmann K, Persidsky R, Wu L, Schellpeper C, Ghorpade A (2005) Role of activated astrocytes in neuronal damage: potential links to HIV-1-associated dementia. Neurotox Res 7:183–192. doi:10.1007/bf03036448
Diggle P (1983) Statistical analysis of spatial point patterns. Academic Press, London, New York
Druga R (2009) Neocortical inhibitory system. Folia Biol (Praha) 55:201–217
Everall IP, Glass JD, McArthur J, Spargo E, Lantos P (1994) Neuronal density in the superior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia. Acta Neuropathol (Berl) 88:538–544
Everall IP, Heaton RK, Marcotte TD, Ellis RJ, McCutchan JA, Atkinson JH, Grant I, Mallory M, Masliah E (1999) Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center. Brain Pathol 9:209–217
Everall I, Hansen L, Masliah E (2005a) The shifting patterns of HIV encephalitis neuropathology. Neurotox Res 8:51–61. doi:10.1007/bf03033819
Everall IP, Hansen LA, Masliah E (2005b) The shifting patterns of HIV encephalitis neuropathology. Neurotox Res 8:51–61
Grant I (2008) Neurocognitive disturbances in HIV. Int Rev Psychiatry 20:33–47. doi:10.1080/09540260701877894
Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group F.t.C (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology 75:2087–2096. doi:10.1212/WNL.0b013e318200d727
Hult B, Chana G, Masliah E, Everall I (2008) Neurobiology of HIV. Int Rev Psychiatry 20:3–13. doi:10.1080/09540260701862086
Kaul M, Lipton S (2006) Mechanisms of neuroimmunity and neurodegeneration associated with HIV-1 infection and AIDS. J NeuroImmune Pharm 1:138–151. doi:10.1007/s11481-006-9011-9
Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410:988–994. doi:10.1038/3507366735073667
Kaluzny SP, Vega SC, Cordosa TP, Shelly AA (1998) S+SpatialStats. New York, Springer
Landau S, Rabe-Hesketh S, Everall IP (2004) Nonparametric one-way analysis of variance of replicated bivariate spatial point patterns. Biom J 46:19–34. doi:10.1002/bimj.200310010
Langford D, Adame A, Grigorian A, Grant I, McCutchan JA, Ellis RJ, Marcotte TD, Masliah E, Group H.N.R.C (2003) Patterns of selective neuronal damage in methamphetamine-user AIDS patients. J Acquir Immune Defic Syndr 34:467–474
Lee M, Schwab C, McGeer PL (2011) Astrocytes are GABAergic cells that modulate microglial activity. Glia 59:152–165. doi:10.1002/glia.21087
Masliah E, Ge N, Achim CL, Hansen LA, Wiley CA (1992) Selective neuronal vulnerability in HIV encephalitis. J Neuropathol Exp Neurol 51:585–593
Masliah E, Ge N, Achim CL, Wiley CA (1995) Differential vulnerability of calbindin-immunoreactive neurons in HIV encephalitis. J Neuropathol Exp Neurol 54:350–357
Masliah E, Heaton RK, Marcotte TD, Ellis RJ, Wiley CA, Mallory M, Achim CL, McCutchan JA, Nelson JA, Atkinson JH, Grant I (1997) Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center. Ann Neurol 42:963–972. doi:10.1002/ana.410420618
Mattson MP, Rychlik B, Chu C, Christakost S (1991) Evidence for calcium-reducing and excitoprotective roles for the calcium-binding protein calbindin-1328 k in cultured hippocampal neurons. Neuron 6:41–51
Patton HK, Zhou ZH, Bubien JK, Benveniste EN, Benos DJ (2000) gp120-induced alterations of human astrocyte function: Na(+)/H(+) exchange, K(+) conductance, and glutamate flux. Am J Physiol Cell Physiol 279:C700–C708
Price R, Brew B (1988) The AIDS dementia complex. J Infect Dis 158:1079–1083
Rossi D, Volterra A (2009) Astrocytic dysfunction: insights on the role in neurodegeneration. Brain Res Bull 80:224–232. doi:10.1016/j.brainresbull.2009.07.012
Rowlingson RS, Diggle PJ (1993) Splancs: spatial point pattern analysis code in S-plus. Technical report, Department of Mathematics, Lancaster University, Lancaster, UK
Samikkannu T, Agudelo M, Gandhi N, Reddy P, Saiyed Z, Nwankwo D, Nair M (2011) Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: implications for neuroAIDS. J Neurovirol 17:230–238. doi:10.1007/s13365-011-0026-5
Thompson KA, McArthur JC, Wesselingh SL (2001) Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia. Ann Neurol 49:745–752. doi:10.1002/ana.1011
Tran PB, Ren D, Miller RJ (2005) The HIV-1 coat protein gp120 regulates CXCR4-mediated signaling in neural progenitor cells. J Neuroimmunol 160:68–76. doi:10.1016/j.jneuroim.2004.11.001
Acknowledgments
Funding for this work was kindly provided by AVERT–The AIDS Education and Research Trust (AVERT, NS26643, RR00722).
IPE is supported by grants R01MH079881, R41MH079728, R25MH074508, R25MH081482, and R21MH078728.
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Roberts, E.S., Chana, G., Nguyen, T.B. et al. The spatial relationship between neurons and astrocytes in HIV-associated dementia. J. Neurovirol. 19, 123–130 (2013). https://doi.org/10.1007/s13365-013-0149-y
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DOI: https://doi.org/10.1007/s13365-013-0149-y