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Inga Kadish, PhD

Inga Kadish, PhD
Assistant Professor
Department of Cell, Developmntl, & Integrative Biology
THT 912 Zip 0006
Phone: 205-934-5940

University of Latvia, Latvia MS 06/85 Human/ Animal Physiology
University of Kuopio, Finland PhD 06/02 Neuroscience/Neurology
University of Kuopio, Finland Post-doc 07/02-01/04 Neuroscience
Univ. of Alabama at Birmingham, USA Post-doc 02/04-06/06 Hypertension/Vascular Biology

Research/Clinical Interest

The role of white matter changes in aging and Alzheimer's disease
The overall goal of my research is to elucidate the role of white matter pathology in the development of age-related cognitive deficits. Currently, our studies have shown two significant changes in white matter pathology with aging malfunctioning of oligodendrocytes and demyelination of axons. Further, cholesterol trafficking is disturbed early in the aging process in the white matter, specifically in astrocytes, and since astrocytes are the main source of cholesterol in the brain, this likely leads to changes in the myelin sheath. Together these changes will lead to a “functional” disconnection in the brain leading to cognitive disturbances. We are investigating these changes in oligodendrocyte dysfunction in the white matter, and the development of cognitive impairments, using a combination of behavioral, immunohistochemical and molecular biology approaches. Furthermore, we have recently discovered changes in the expression of epigenetic markers with aging, i.e., changes in HDACs and DNMTs in the white matter. This novel discovery has lead to potential new therapies for age-related white matter pathology. A second research interest is the role of vascular pathology in Alzheimer’s disease, specifically hypertension and the relation between white matter infarcts and AD pathology. While clinical data strongly suggest that small infarcts contribute significantly to cognitive decline, the causal relationship is still not clearly defined. Our studies have shown that small ischemic infarcts both increase Aß deposition and decrease cognition. Furthermore, we have found that white matter infarcts (compared to grey matter infarcts) have a significantly worse outcome. Currently we are focusing on the role of hypertension in age-related cerebral dysfunction and Alzheimer’s disease. Some of my current studies include the use of therapeutic agents (i.e., amyloid β binding peptides) that may be promising in the alleviation or delay of age-related neural and cognitive changes. Further, currently, we are investigating the role of obesity, and/or caloric restriction and hunger in the development of cognitive deficits in AD.

Selected Publications

  1. Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations with Aging. Chen KC, Blalock EM, Curran-Rauhut MA, Kadish I, Blalock SJ, Brewer L, Porter NM, Landfield PW. Endocrinology. 2013 Jun 4. [Epub ahead of print] 3736296 
  2. Hunger in the absence of caloric restriction improves cognition and attenuates Alzheimer's disease pathology in a mouse model. Dhurandhar EJ, Allison DB, van Groen T, Kadish I.  PLoS One. 2013;8(4):e60437. doi: 10.1371/journal.pone.0060437. Epub 2013 Apr 2 23565247 
  3. Long-Term Pioglitazone Treatment Improves Learning and Attenuates Pathological Markers in a Mouse Model of Alzheimer's Disease. Searcy JL, Phelps JT, Pancani T, Kadish I, Popovic J, Anderson KL, Beckett TL, Murphy MP, Chen KC, Blalock EM, Landfield PW, Porter NM, Thibault O. J Alzheimers Dis. 2012 Apr 10. [Epub ahead of print] 22495349 
  4. Disrupting function of FK506-binding protein 1b/12.6 induces the Ca²+-dysregulation aging phenotype in hippocampal neurons. Gant JC, Chen KC, Norris CM, Kadish I, Thibault O, Blalock EM, Porter NM, Landfield PW. J Neurosci. 2011 Feb 2;31(5):1693-703 21289178 
  5. Transgenic AD model mice, effects of potential anti-AD treatments on inflammation, and pathology. van Groen T, Miettinen P, Kadish I. J Alzheimers Dis. 2011;24(2):301-13. 21239852 
  6. Age-related brain pathology in Octodon degu: blood vessel, white matter and Alzheimer-like pathology. van Groen T, Kadish I, Popović N, Popović M, Caballero-Bleda M, Baño-Otálora B, Vivanco P, Rol MÁ, Madrid JA. Neurobiol Aging. 2011 Sep;32(9):1651-61. Epub 2009 Nov 11. 19910078 
  7. Lesion-induced hippocampal plasticity in transgenic Alzheimer's disease mouse models: influences of age, genotype, and estrogen. Kadish I, van Groen T. J Alzheimers Dis. 2009;18(2):429-45. 19584452 
  8. Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease. Handattu SP, Garber DW, Monroe CE, van Groen T, Kadish I, Nayyar G, Cao D, Palgunachari MN, Li L, Anantharamaiah GM. Neurobiol Dis. 2009 Jun;34(3):525-34. Epub 2009 Apr 1. 19344763 
  9. Hippocampal and cognitive aging across the lifespan: a bioenergetic shift precedes and increased cholesterol trafficking parallels memory impairment. Kadish I, Thibault O, Blalock EM, Chen KC, Gant JC, Porter NM, Landfield PW. J Neurosci. 2009 Feb 11;29(6):1805-16. 19211887 
  10. Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome. Zhang J, Luo B, Tang L, Wang Y, Stockard CR, Kadish I, Van Groen T, Grizzle WE, Ponnazhagan S, Fallon MB. Gastroenterology. 2009 Mar;136(3):1070-80. Epub 2008 Dec 3. 19109954 
  11. In vitro and in vivo staining characteristics of small, fluorescent, Abeta42-binding D-enantiomeric peptides in transgenic AD mouse models. van Groen T, Kadish I, Wiesehan K, Funke SA, Willbold D. ChemMedChem. 2009 Feb;4(2):276-82. 19072935 
  12. Reduction of Alzheimer's disease amyloid plaque load in transgenic mice by D3, A D-enantiomeric peptide identified by mirror image phage display. van Groen T, Wiesehan K, Funke SA, Kadish I, Nagel-Steger L, Willbold D. ChemMedChem. 2008 Dec;3(12):1848-52.  19016284 
  13. Subfield and layer-specific depletion in calbindin-D28K, calretinin and parvalbumin immunoreactivity in the dentate gyrus of amyloid precursor protein/presenilin 1 transgenic mice. Popović M, Caballero-Bleda M, Kadish I, Van Groen T. Neuroscience. 2008 Jul 31;155(1):182-91. Epub 2008 May 24. 18583063 
  14. DNA methylation impacts on learning and memory in aging. Liu L, van Groen T, Kadish I, Tollefsbol TO. Neurobiol Aging. 2009 Apr;30(4):549-60. Epub 2007 Sep 11. Review 17850924 
  15. Hippocampal expression analyses reveal selective association of immediate-early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats. Rowe WB, Blalock EM, Chen KC, Kadish I, Wang D, Barrett JE, Thibault O, Porter NM, Rose GM, Landfield PW. J Neurosci. 2007 Mar 21;27(12):3098-110. 17376971 
  16. Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice. van Groen T, Kiliaan AJ, Kadish I. Neurobiol Dis. 2006 Sep;23(3):653-62. 16829076 
  17. Harnessing the power of gene microarrays for the study of brain aging and Alzheimer's disease: statistical reliability and functional correlation. Blalock EM, Chen KC, Stromberg AJ, Norris CM, Kadish I, Kraner SD, Porter NM, Landfield PW. Ageing Res Rev. 2005 Nov;4(4):481-512. Epub 2005 Oct 27 16257272 
  18. Calcineurin triggers reactive/inflammatory processes in astrocytes and is upregulated in aging and Alzheimer's models. Norris CM, Kadish I, Blalock EM, Chen KC, Thibault V, Porter NM, Landfield PW, Kraner SD. J Neurosci. 2005 May 4;25(18):4649-58. 15872113 
  19. Transgenic AD model mice, effects of potential anti-AD treatments on inflammation and pathology. van Groen T, Kadish I. Brain Res Brain Res Rev. 2005 Apr;48(2):370-8. 15850676 
  20. Retrosplenial cortex lesions of area Rgb (but not of area Rga) impair spatial learning and memory in the rat. van Groen T, Kadish I, Wyss JM. Behav Brain Res. 2004 Oct 5;154(2):483-91 15313037 
  21. Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Wang J, Tanila H, Puoliväli J, Kadish I, van Groen T. Neurobiol Dis. 2003 Dec;14(3):318-27 14678749 
  22. Age-related decline in spatial learning and memory: attenuation by captopril. Wyss JM, Kadish I, van Groen T. Clin Exp Hypertens. 2003 Oct;25(7):455-74 14596369 
  23. Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions. van Groen T, Liu L, Ikonen S, Kadish I. Neuroscience. 2003;119(4):1185-97. 12831872 
  24. The entorhinal cortex of the mouse: organization of the projection to the hippocampal formation. van Groen T, Miettinen P, Kadish I. Hippocampus. 2003;13(1):133-49. 12625464 
  25. Differences in lesion-induced hippocampal plasticity between mice and rats. Kadish I, Van Groen T. Neuroscience. 2003;116(2):499-509 12559105 
  26. Low levels of estrogen significantly diminish axonal sprouting after entorhinal cortex lesions in the mouse. Kadish I, Van Groen T. J Neurosci. 2002 May 15;22(10):4095-102. 12019328