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

Abstract

This study determined whether olfactory bulb lesions would affect trophic support to its afferent, the horizontal limb of the diagonal band of Broca (hIDBB), and if estrogen would ameliorate the effects of neural injury in this circuit. NMDA injections into the olfactory bulb resulted in neural injury as indicated by cell loss and increased glial fibrillary acidic protein immunoreactivity. Olfactory bulb lesions severely reduced BDNF expression in its afferent, the hIDBB, while NGF was only reduced in lesioned animals deprived of estrogen. In the olfactory bulb itself, lesions increased BDNF expression, but not NGF. Paradoxically, bulb lesions up-regulated both NGF and BDNF in another target of the hIDBB, the cingulate cortex. Moreover, olfactory bulb lesions affected choline uptake and ChAT activity locally, as well as in the cingulate cortex. Estrogen significantly attenuated the lesion-induced loss of choline uptake in the cingulate cortex, but not at the primary lesion site. Collectively, these results indicate that neural injury to one limb of the forebrain cholinergic system may result in collateral damage to other limbs of this system, suggesting a mechanism for the progression of neurodegenerative diseases, such as Alzheimer's disease, that involve the cholinergic system. Furthermore, these data also indicate that estrogen selectively attenuates certain lesion-induced deficits.