Jingdong Zhang, PhD
Member Huangui Xiong's laboratory
Keywords: HIV-1 associated neurocognitive disorder (HAND); White matter damage; Corpus callosum and deep white matter; Microglia; Astrocyte; Oligodendrocyte
HAND remains a crucial problem that deteriorates the life quality of AIDS patient even they live longer in era of highly active antiretroviral therapy (HAART). Devastative neuron degeneration observed in HIV-1 encephalitis (HIVE) decades ago has been shifted to diffusive and focal injury especially in white matter in HAART era. Mechanism is unknown up to date. My research will aim to possible involvement of microglia and astrocyte in pathogenesis of this diffusive and/or focal white matter damage. I’ll utilize brain tissues from both HIVE autopsy in our brain bank of UNMC, brain bank of NNTC.org and simian immunodeficiency virus (SIV) infected monkey, attempt to detect any element that may play a pivotal role in situ, then apply it to in vivo or ex vivo rat white matter tissue, or cultured rat oligodendrocyte to investigate possible mechanism through which the element may induce a lesion. Lipopolysaccharide (LPS) is able to activate both microglia and astrocyte with microglia dominant; therefore, LPS treatment or injection will be used in rat as a model to study the mechanism of damage if evidence for participation of microglia or astrocyte in HIV or SIV associated white matter damage is ample.
Long term goals:
1. In addition to HIVE, white matter damage has been noted in several other neurological diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis (MS).The latter two were considered to be predominant white matter injury, but the mechanism is still not clear. For instance, the EAE model was widely applied in MS studies; although this model can mimic symptoms and neuropathy of MS, it is not good for exploration of the pathogenesis. In human and animal studies, it could not answer what had happened on the myelin sheath before it produced antibody against the myelin sheath and why the subject has to generate antibody to its own myelin sheath. Is there any truly primary demyelination and what is the mechanism?
2. Following exploration of the mechanism of the white matter damage, try to find any reagent or method that can stop deterioration of the disorder and/or reverse the pathogenic procedure.
Zhang JD, Luo PF, Ro JY and Xiong HG: Jaw muscle spindle afferents coordinate multiple orormotor nuclei via common premotor neurons, electrophysiology and anatomical studies in the rat. Brain Research 1489:37-47 2012.
Zhang JD, Liu JN, Fox HS and Xiong HG: N-methyl-D-aspartate receptor – mediated axonal injury in adult rat corpus callosum. J. Neurosci Res 2012 91(2):240-8.
Zhang JD, Liang HC, Luo PF and Xiong HG: Unraveling a masticatory - oculomotor neural pathway in rat: Implications for a pathophysiological neural circuit in human? Int J Physiol Pathophysiol Pharmacol. 3(4):280-7.
Zhang JD, Liu JN, Katafiasz B, Fox H and Xiong HG: HIV-1 gp120-Induced axonal injury detected by accumulation of β-amyloid precursor protein in adult rat corpus callosum. J Neuroimmune Pharmacol. 6(4)650-657, 2011.
Luo PF, Zhang JD, Yang R and Pendlebury W: Neuronal circuitry and synaptic organization of trigeminal proprioceptive afferents mediating tongue movement and jaw-tongue coordination via hypoglossal premotor neurons. European J Neurosci. 23:3269-3283 2006.
Zhang JD, Luo PF and Pendlebury WW: Monosynaptic Circuitry of Trigeminal Proprioceptive Afferents Coordinating Jaw Movement with Visceral and Laryngeal Activities in Rats. Neuroscience 135:497-505 2005.