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The Journal of Neuroscience, June 1, 1999, 19(11):4616-4626
Immunohistochemical Evidence of Seizure-Induced Activation of
trk Receptors in the Mossy Fiber Pathway of Adult Rat
Hippocampus
Devin K.
Binder1,
Mark
J.
Routbort1, and
James O.
McNamara1, 2, 3, 4
Departments of 1 Neurobiology, 2 Medicine
(Neurology), 3 Pharmacology, and 4 Molecular
Cancer Biology, Duke University Medical Center, Durham, North Carolina
27710
Recent work suggests that limiting the activation of the trkB
subtype of neurotrophin receptor inhibits epileptogenesis, but whether
or where neurotrophin receptor activation occurs during epileptogenesis
is unclear. Because the activation of trk receptors involves the
phosphorylation of specific tyrosine residues, the availability of
antibodies that selectively recognize the phosphorylated form of trk
receptors permits a histochemical assessment of trk receptor
activation. In this study the anatomy and time course of trk receptor
activation during epileptogenesis were assessed with
immunohistochemistry, using a phospho-specific trk antibody. In
contrast to the low level of phosphotrk immunoreactivity constitutively expressed in the hippocampus of adult rats, a striking induction of
phosphotrk immunoreactivity was evident in the distribution of the
mossy fibers after partial kindling or kainate-induced seizures.
The anatomic distribution, time course, and threshold for
seizure-induced phosphotrk immunoreactivity correspond to the
demonstrated pattern of regulation of BDNF expression by seizure activity. These results provide immunohistochemical evidence that trk
receptors undergo activation during epileptogenesis and suggest that
the mossy fiber pathway is particularly important in the pro-epileptogenic effects of the neurotrophins.
Key words:
neurotrophins; BDNF; kindling; epilepsy; epileptogenesis; trk receptors
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114616-11$05.00/0
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