Reproductive and Developmental Toxicity, and Neurotoxicity of a Tropomyosin-Related Kinase A Inhibitor, ASP7962, in Rats

概要

A family of three tropomyosin-related kinases (TrkA, TrkB, and TrkC)
regulates the survival, development and function of neurons in both the central
and peripheral nervous systems, and activated by NGF, BDNF, NT-3, 4 and 5
(Skaper, 2012, 2018). Inhibition of NGF induces the loss of these neurons during
development due to cell death (Gorin & Johnson, 1979). Anti-NGF antibody
induces morphological atrophy of the superior cervical ganglion with reduced
neuronal number in rats (Gorin & Johnson, 1980). NGF binds to TrkA with high
affinity and p75 neurotrophin receptor with low affinity (Kaplan et al., 1991).
NGF supports the survival of sensory and sympathetic neurons. Mice lacking
NGF show neuronal cell loss in the sensory and sympathetic ganglia (Crowley et
al., 1994). In TrkA lacking mice, severe sensory and sympathetic neuropathies,
and neuronal cell loss in the trigeminal, sympathetic and dorsal root ganglia were
observed (Smeyne et al., 1994). BDNF-TrkB signaling regulates the synaptic
plasticity in the brain. There is also a role of TrkB in hippocampal long-term
potentiation and learning (Minichiello, 2009). Mutant mice lacking BDNF show
deficits in coordination and balance which are related to the degeneration in the
sensory ganglia including the vestibular ganglion (Ernfors et al., 1994). ...

この論文で使われている画像