Local and cortical effects of olfactory bulb lesions on trophic support and cholinergic function and their modulation by estrogen

This study determined whether olfactory bulb lesions would affect trophic s upport to its afferent, the horizontal limb of the diagonal band of Broca ( hIDBB), and if estrogen would ameliorate the effects of neural injury in th is circuit. NMDA injections into the olfactory bulb resulted in neural inju ry as indicated by cell loss and increased glial fibrillary acidic protein immunoreactivity. Olfactory bulb lesions severely reduced BDNF expression i n its afferent, the hIDBB, while NGF was only reduced in lesioned animals d eprived of estrogen. In the olfactory bulb itself, lesions increased BDNF e xpression, but not NGF. Paradoxially, bulb lesions up-regulated both NGF an d BDNF in another target of the hIDBB, the cingulate cortex. Moreover, olfa ctory bulb lesions affected choline uptake and ChAT activity locally, as we ll as in the cingulate cortex. Estrogen significantly attenuated the lesion -induced loss of choline uptake in the cingulate cortex, but not at the pri mary lesion site. Collectively, these results indicate that neural injury t o one limb of the forebrain cholinergic system may result in collateral dam age to other limbs of this system, suggesting a mechanism for the progressi on of neurodegenerative diseases, such as Alzheimer's disease, that involve the cholinergic system. Furthermore, these data also indicate that estroge n selectively attenuates certain lesion-induced deficits. (C) 2000 John Wil ey & Sons, Inc.