Hippocampal Excitability Increases during the Estrous Cycle in the Rat: A Potential Role for Brain-Derived Neurotrophic Factor

Scharfman, Helen E.; Mercurio, Thomas C.; Goodman, Jeffrey H.; Wilson, Marlene A.; MacLusky, Neil J.

doi:10.1523/jneurosci.23-37-11641.2003

Cited by 245 publications

(284 citation statements)

References 79 publications

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“…Interestingly, the changes were analogous to those that are observed after BDNF is superfused onto a normal male hippocampal slice, or the changes detected in transgenic mice that overexpress BDNF [45,95]. These could be blocked by a trk receptor antagonist [86]. Together, these data supported the hypothesis that physiological levels of estradiol could increase BDNF in hippocampus.…”

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampusupporting

confidence: 72%

“…Indeed, patches of CA3 pyramidal cell somata were darkly immunoreactive [86]. The high levels of BDNF waned after the morning of estrus, appearing lower on the morning of metestrus (Figure 4; [86]). …”

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 97%

“…For example, in some brain regions, estradiol administration does not always restore BDNF levels after ovariectomy [84], although there are some potential explanations for this, such as the fact that retrograde transport may remove BDNF from the structure where it is examined, or the pattern of ER expression determines the ultimate effect on BDNF levels (for discussion, see [84]). Even in hippocampus, some investigators find that the majority of BDNF expression modulated by estrogen is in CA1-CA3 [38,85] whereas others find it in the dentate gyrus [82,86].…”

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 99%

“…In addition, BDNF protein levels were studied instead of mRNA, because BDNF mRNA does not always predict protein expression. These studies were informative because they showed that on the morning of proestrus, BDNF protein was elevated relative to ovariectomized rats, and it was elevated in the mossy fibers in particular, suggesting that estradiol elevated the level of BDNF in the same areas where it is normally expressed, rather than ectopic locations ( Figure 4, [86]). …”

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 99%

“…Mossy fiber transmission and Schaffer collateral transmission, the second and third synapse of the trisynaptic circuit, were enhanced ( Figure 4; [86]). Interestingly, the changes were analogous to those that are observed after BDNF is superfused onto a normal male hippocampal slice, or the changes detected in transgenic mice that overexpress BDNF [45,95].…”

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 99%

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Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

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In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy.

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Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampusupporting

confidence: 72%

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 97%

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 99%

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 99%

Section: Mechanisms For Estrogen-bdnf Interactions In Hippocampumentioning

confidence: 99%

See 3 more Smart Citations

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

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267

202

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Seizures and reproductive function: Insights from female rats with epilepsy

Scharfman

Kim

Hintz

et al. 2008

Annals of Neurology

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OBJECTIVE-Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome (PCOS), but it has been difficult to dissociate the effects of epilepsy per se from the role of antiepileptic drugs (AEDs). To distinguish the effects of chronic seizures from AEDs, we used the laboratory rat, where an epileptic condition can be induced without concomitant AED treatment.METHODS-Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus (SE), which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed "epileptic." Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop SE. Ovarian cyclicity and weight gain were evaluated for 2-3 months. Serum hormone levels were assayed from trunk blood, collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS-Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if SE did not occur. Ovarian cysts and weight gain were significantly greater in epileptic rats than controls, whether rats maintained cyclicity or not. Serum testosterone was elevated in epileptic rats, but estradiol, progesterone and prolactin were not. INTERPRETATIONS-The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels. Although caution is required when comparing female rats to women, the data suggest that epilepsy per se may be sufficient to induce abnormalities in the control of the ovary.

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Ultrastructural localization of estrogen receptor β immunoreactivity in the rat hippocampal formation

et al. 2005

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Several lines of evidence indicate that estrogen affects hippocampal synaptic plasticity through rapid nongenomic mechanisms, possibly by binding to plasma membrane estrogen receptors (ERs). We have previously shown that ERalpha immunoreactivity (ir) is in select interneuron nuclei and in several extranuclear locations, including dendritic spines and axon terminals, within the rat hippocampal formation (Milner et al., [2001] J Comp Neurol 429:355). The present study sought to determine the cellular and subcellular locations of ERbeta-ir. Coronal hippocampal sections from diestrus rats were immunolabeled with antibodies to ERbeta and examined by light and electron microscopy. By light microscopy, ERbeta-ir was primarily in the perikarya and proximal dendrites of pyramidal and granule cells. ERbeta-ir was also in a few nonprincipal cells and scattered nuclei in the ventral subiculum and CA3 region. Ultrastructural analysis revealed ERbeta-ir at several extranuclear sites in all hippocampal subregions. ERbeta-ir was affiliated with cytoplasmic organelles, especially endomembranes and mitochondria, and with plasma membranes primarily of principal cell perikarya and proximal dendrites. ERbeta-ir was in dendritic spines, many arising from pyramidal and granule cell dendrites. In both dendritic shafts and spines, ERbeta-ir was near the perisynaptic zone adjacent to synapses formed by unlabeled terminals. ERbeta-ir was in preterminal axons and axon terminals, associated with clusters of small, synaptic vesicles. ERbeta-labeled terminals formed both asymmetric and symmetric synapses with dendrites. ERbeta-ir also was detected in glial profiles. The cellular and subcellular localization of ERbeta-ir was generally similar to that of ERalpha, except that ERbeta was more extensively found at extranuclear sites. These results suggest that ERbeta may serve primarily as a nongenomic transducer of estrogen actions in the hippocampal formation.

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Hippocampal Excitability Increases during the Estrous Cycle in the Rat: A Potential Role for Brain-Derived Neurotrophic Factor

Cited by 245 publications

References 79 publications

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Seizures and reproductive function: Insights from female rats with epilepsy

Ultrastructural localization of estrogen receptor β immunoreactivity in the rat hippocampal formation

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