Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures

Stress, which can precipitate and exacerbate depression, causes atrophy and in severe cases death of hippocampal neurons. Atrophy of the hippocampus h as also been observed in patients suffering from recurrent major depression . The present study examines the influence of electroconvulsive seizures, o ne of the most effective treatments for depression, on the morphology and s urvival of hippocampal neurons. The results demonstrate that chronic admini stration of electroconvulsive seizures induces sprouting of the granule cel l mossy fiber pathway in the hippocampus. This sprouting is dependent on re peated administration of electroconvulsive seizures, reaches a maximum 12 d ays after the last treatment and is long lasting (i.e. up to six months). E lectroconvulsive seizure-induced sprouting occurs in the absence of neurona l loss, indicating that sprouting is not a compensatory response to cell de ath. This is different from the sprouting induced by kindling or excitotoxi n treatment, which induce cell death along with recurrent seizures. Electro convulsive seizure-induced sprouting is significantly diminished in brain d erived neurotrophic factor heterozygote knockout mice, indicating that this neurotrophic factor contributes to mossy Fiber sprouting. However, infusio n of brain-derived neurotrophic factor into the hippocampus does not induce sprouting of the mossy fiber pathway. The results demonstrate that chronic administration of electroconvulsive se izures induces mossy fiber sprouting and suggest that increased expression of brain-derived neurotrophic factor is necessary, but not sufficient for t he induction of this sprouting. Although the functional consequences remain unclear, sprouting of the mossy fiber pathway would appear to oppose the a ctions of stress and could thereby contribute to the therapeutic actions of electroconvulsive seizure therapy. (C) 1998 IBRO. Published by Elsevier Sc ience Ltd.