Brain Neoplasms; DNA Virus Infections; Nervous System Diseases; Parasitic Diseases; Tumor Virus Infections; Encephalitis, Viral; Sleep Disorders, Circadian Rhythm; Trauma, Nervous System; Central Nervous System Viral Diseases; Central Nervous System Parasitic Infections
Molecular Virology: Virology laboratories
Relationship of Research to Neurological Disease:
Developmental processes may underlie a number of neurological problems. These relate to normal and abnormal development. Many childhood behavioral disabilities may relate to underlying problems in brain development. We find, for instance, that raising neurons from any region of the brain in the absence of glutamate neurotransmitter stimulation results, at a later point in neuronal development, in a hypersensitivity to glutamate, neuronal hyperexcitability (seizure-like activity), and cell death. These problems can be reduced to varying degrees by a number of peptide modulators of glutamate release and response. Another example of clinical relevance is our finding that the primary inhibitory transmitter in the brain, GABA, has excitatory actions after neuronal trauma, potentially resulting in additional secondary brain injury due to the potential loss of inhibition in affected brain circuits. An important theme in the context of this research program is the parallel that occurs between normal development and recovery after neuronal injury. Understanding normal brain development facilitates the understanding of the steps that may occur as neurons recovery from injury.
Extensive Research Description
Current Research Program We are particularly interested in the mechanisms where neurotransmitters in early development may play a role in establishing and stabilizing functional neuronal circuits. To this end we use a variety of approaches including electrophysiology, tissue culture, molecular biology, ultrastructural immunocytochemistry, and digital imaging to study the general question from converging perspectives relating both to neuronal structure and function. A particular area of interest within the brain is the hypothalamus that acts as a homeostatic regulator controlling the endocrine system, biological rhythms, cardiovascular system, and general autonomic tone.
- Tsunematsu,T, Fu LY, Yamanaka A, Ichiki K, Tanoue A, Sakurai T, van den Pol AN (2008) Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons- implications for water homeostasis. J. Neurosci. 28: 228-238.
- Huang H, van den Pol AN. (2007) Rapid direct excitation and long-lasting enhancement of NMDA response by group I metabotropic glutamate receptor activation of hypothalamic melanin-concentrating hormone neurons. J. Neurosci. 27: 11560-11572.
- Ho WSC, van den Pol AN (2007) Bystander attenuation of neuronal and astrocyte intercellular communication by murine cytomegalovirus infection of glia J. Virol. 2007 81: 7286-7292.
- Huang H, Acuna-Goycolea C, Li Y, Cheng HM, Obrietan K, van den Pol AN. (2007) Cannabinoids excite hypothalamic melanin-concentrating hormone but inhibit hypocretin/orexin neurons: implications for cannabinoid actions on food intake and cognitive arousal. J. Neurosci. 27: 4870-4881.