Dendritic and spine alterations in areas 9 and 17 in schizophrenia and Huntington chorea and the role of neuroleptic exposure

Latchman Somenarain, Liesl B. Jones

Department of Biological Sciences, Lehman College, New York, USA.
Department of Biology/MLT, Bronx Community College, New York, USA.

DOI: 10.4236/ojpsych.2012.23032                

Abstract

Recent morphological studies in schizophrenia suggest atrophic changes in the neuropil of the prefrontal cortex. Most recently, we showed a schizophrenia-associated decrease in MAP2 in schizophrenia, which we believed is not due to neuroleptic exposure. MAP2 is a very important protein in the assembly of micro-tubule in neurons; therefore, it plays a major role in neuronal processes like dendrites, spines and synapses. Additionally, recent studies from our lab showed decreases in dendrites in area 32 and area 9. In this study we examined the dendrites and spines in area 9 and 17 to determine if neuroleptic drugs play a role. Huntington’s patients take neuroleptics similar to schizophrenics; therefore, by comparing the two groups to controls we can determine if neuroleptics play a role in the deficits reported in schizophrenia. Our results showed a significant decrease in both basal dendrites and spines for both layers III and V in area 9 in schizophrenia compared to controls. The Huntington’s brains, on the other hand, showed no significant difference compared to controls. In area 17, there was also no significant difference when comparing the three groups. The data suggest that neuroleptic drugs may not be responsible for the changes observed in schizophrenia.

Keywords

Schizophrenia; Huntington; Neuroleptic; Spines; Dendrites; Pyramidal Cells; Prefrontal Cortex; Area 9 and Area 17

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Pakkenberg, B. (1993) Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical dissectors. Biological Psychiatry, 34, 768-772. doi:10.1016/0006-3223(93)90065-L
[2]	Goldman-Rakic, P.S. and Selemon, L.D. (1997) Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophrenia Bulletin, 23, 437-458. doi:10.1093/schbul/23.3.437
[3]	Beasley, C.L. and Reynolds, G.P. (1997) Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenic. Schizophrenia Research, 24, 349-355. doi:10.1016/S0920-9964(96)00122-3
[4]	Glantz L.A. and Lewis, D.A. (1997) Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Archives of General Psychiatry, 54, 943-952. doi:10.1001/archpsyc.1997.01830220065010
[5]	Garey, L.J., Ong, W.Y., Patel, T.S., Kanani, M., Davis, A. and Mortimer, A.M. (1998) Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. Journal of Neurology Neurosurgery Psychiatry, 65, 446-453. doi:10.1136/jnnp.65.4.446
[6]	Selemon, L.D. and Goldman-Rakic, P.S. (1999) The reduced neuropil hypothesis: A circuit based model of schizophrenia. Biological Psychiatry, 45, 17-25. doi:10.1016/S0006-3223(98)00281-9
[7]	Buxhoeveden, D., Ror, E. and Switala, A. (2000) Reduced interneuronal space in schizophrenia. Biological Psychiatry, 47, 681. doi:10.1016/S0006-3223(99)00275-9
[8]	Glantz, A.L. and Lewis, D.A. (2000) Decrease dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Archives of General Psychiatry, 57, 65-73. doi:10.1001/archpsyc.57.1.65
[9]	Andreasen, N.C. (2000) Schizophrenia: The fundamental questions. Brain Research Review, 31, 106-112. doi:10.1016/S0165-0173(99)00027-2
[10]	Thune, J.J., Uylings, H.B.M. and Pakkenberg, B. (2001) No deficit in total number of neurons in the prefrontal cortex in schizophrenics. Journal of Psychiatric Research, 35, 15-21. doi:10.1016/S0022-3956(00)00043-1
[11]	Jones, L., Johnson, N. and Byne, W. (2002) Alterations in MAP2 immunocytochemistry in area 9 and 32 of schizophrenic prefrontal cortex. Psychiatry Research Neuroimaging, 9, 3621-3625.
[12]	Broadbelt, K. and Jones, L.B. (2008) Evidence of altered calmodulin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex. Journal of Psychiatric Research, 42, 612-621. doi:10.1016/j.jpsychires.2007.07.006
[13]	Broadbelt, K., Rampersaud, A. and Jones, L.B. (2006) Evidence of altered neurogranin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex. Schizophrenia Research, 87, 6-14. doi:10.1016/j.schres.2006.04.028
[14]	Broadbelt, K., Byne, W.B. and Jones, L.B. (2002) Evidence for a decrease in primary and secondary basilar dendrites on pyramidal cells in area 32 of schizophrenic prefrontal cortex. Schizophrenia Research, 58, 75-81. doi:10.1016/S0920-9964(02)00201-3
[15]	Somenarain, L. and Jones, L. (2010) A comparative study of MAP2 immunostaining in areas 9 and 17 in schizophrenia and Huntington chorea. Journal of Psychiatric Research, 44, 694-699. doi:10.1016/j.jpsychires.2009.12.006
[16]	Somenarain, L. (2011) Neuropathology of the prefrontal cortex neuropil in schizophrenia. Psychiatric Disorders Trends and Developments, Intech, 1-18.
[17]	Powell, T.P.S. (1981) Certain aspects of the intrinsic organization of the cerebral cortex. Raven Press, New York, 1-19.
[18]	Mates, S.L. and Lund, J.S. (1983) Spine formation and maturation of type I synapses on spiny stelate neurons in primary visual cortex. Journal of Comparative Neurology, 221, 91-97. doi:10.1002/cne.902210107
[19]	Peters, A. and Kaiserman-Abramof, I.R. (1970) The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. American Journal of Anatomy, 127, 321-355. doi:10.1002/aja.1001270402
[20]	Daviss, S.R. and Lewis, D.A. (1995) Local circuit neurons of the prefrontal cortex in schizophrenia: Selective increase in the density of calbindin-immunoreactive neurons. Psychiatric Research, 59, 81-96. doi:10.1016/0165-1781(95)02720-3
[21]	Selemon, L.D., Rajkowska, G. and Goldman-Rakic, P.S. (1995) Abnormally high neuronal density in the schizophrenic cortex: A morphometric analysis of prefrontal area 9 and occipital area 17. Archives of General Psychiatry, 52, 805-818. doi:10.1001/archpsyc.1995.03950220015005
[22]	Arnold, S.E., Hyman, B.T., Van Hoesen, G.W. and Damasio, A.R. (1991) Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Archives of General Psychiatry, 48, 625-632. doi:10.1001/archpsyc.1991.01810310043008
[23]	Lidow, M.S., Songa, Z., Castnerb, S.A., Allenc, P.B., Greengarde, P. and Goldman-Rakic, P.S. (2001) Antipsychotic treatment induces alterations in dendrite and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex. Biological Psychiatry, 49, 1-12. doi:10.1016/S0006-3223(00)01058-1
[24]	Gur, R.E., Maany, V., Mozley, P.D., Swanson, C., Bilker, W. and Gur, R.C. (1998) Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. American Journal of Psychiatry, 155, 1711-1717.
[25]	Smiley, J.F., Williams, S.M. and Szigeti, K. (1992) Light electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex. Comparative Neurology, 321, 325-335. doi:10.1002/cne.903210302
[26]	Andreasen, N.C., Arndt, S., Swayze, V., Cizadlo, T., Flaum, M. and O’Leary, D. (1994) Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science, 266, 294-298. doi:10.1126/science.7939669
[27]	Buchsbaum, M.S., Someya, T., Teng, C.Y., Abel, L., Chin, S. and Najafi, A. (1996) PET and MRI of the thalamus in never-medicated patients with schizophrenia. American Journal of Psychiatry, 153, 191-199.
[28]	Byne, W., Jones, L.B., Kemether, E., Haroutunian, V. and Davis, K.L. (1997) Towards localization of thalamic pathology in schizophrenia. APA Abstract, NR544.
[29]	Byne, W., Buchsbaum, M.S., Kemether, E., Hazlett, E.A., Shinwari, A., Mitropoulou, V. and Siever, L.J. (2001) Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder. Archives of General Psychiatry, 58, 133-140. doi:10.1001/archpsyc.58.2.133
[30]	Byne, W., Buchsbaum, M.S., Mattiace, L. A., Hazlett, A., Kemether, E., Elhakem, S.L., Purohit, D.P., Haroutunian, V. and Jones, L. (2002) Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. American Journal of Psychiatry, 159, 59-65. doi:10.1176/appi.ajp.159.1.59
[31]	Jones, G.E. (1997) Cortical development and thalamic pathology in schizophrenia. Schizophrenia, 23, 483-501. doi:10.1093/schbul/23.3.483
[32]	Popken, J.G., Bunney, E.W., Potkin, G.S. and Jones, G.E. (2000) Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. Proceedings of the National Academy of Sciences USA, 97, 9276-9280. doi:10.1073/pnas.150243397
[33]	Young, K., Manaye, K.F., Liang, C., Hicks, P.B. and German, D.C. (2000) Reduced number of MD and anterior thalamic neurons in schizophrenia. Biological Psychiatry, 47, 944-953. doi:10.1016/S0006-3223(00)00826-X