Nerve growth factor, interoception, and sympathetic neuron: lesson from congenital insensitivity to pain with anhidrosis.
Nerve growth factor (NGF) is a well-known neurotrophic factor essential for the survival and maintenance of sensory and sympathetic neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is a genetic disorder due to loss-of-function mutations in the NTRK1 (also known as TRKA) gene encoding TrkA, a receptor tyrosine kinase for NGF. Patients with CIPA provide us a rare opportunity to explore the developmental and physiological function of the NGF-dependent neurons in behavior, cognitive, and mental activities that are not available in animal studies. Here, I discuss the significance of findings that patients with CIPA lack NGF-dependent neurons, including interoceptive polymodal receptors, sympathetic postganglionic neurons, and probably several types of neurons in the brain. They also exhibit characteristic emotional behavior or problems. Together, the NGF-TrkA system is essential for the establishment of a neural network for interoception and homeostasis that may underlie 'gut feelings'. Thus, NGF-dependent neurons play a crucial role in emotional experiences and decision-making processes. Prospective studies focused on these neurons might provide further insights into the neural basis of human emotion and feeling.
Indo
Yasuhiro
Y
Department of Pediatrics, Kumamoto University Hospital, Honjo 1-1-1, Kumamoto 860-8556, Japan. yindo@kumamoto-u.ac.jp
D000339:Affect / Q000502:physiology; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D020932:Nerve Growth Factor / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics; D017833:Visceral Afferents / Q000378:metabolism / Q000503:physiopathology*
D020932:Nerve Growth Factor; D020917:Receptor, trkA