17β-Estradiol Increases Astrocytic Vascular Endothelial Growth Factor (VEGF) in Adult Female Rat Hippocampus

Abstract

Vascular endothelial growth factor (VEGF) is critical to angiogenesis and vascular permeability. It is also important in the endocrine system, in which VEGF mediates the vascular effects of estrogens in target tissues such as the uterus, a response attributed to an estrogen response element on the VEGF gene. Here we asked whether 17β-estradiol increases VEGF levels in the brain. We focused on the hippocampus, in which 17β-estradiol and VEGF both have important actions, and used immunocytochemistry to evaluate VEGF protein. VEGF immunoreactivity was compared in adult female rats sampled during the estrous cycle when serum levels of 17β-estradiol peak (proestrous morning) as well as when they are low (metestrous morning). In addition, adult rats were ovariectomized and compared after treatment with 17β-estradiol or vehicle. The results demonstrated that VEGF immunoreactivity was increased when serum levels of 17β-estradiol were elevated. Confocal microscopy showed that VEGF immunofluorescence was predominantly nonneuronal, often associated with astrocytes. Glial VEGF labeling was primarily punctate rather than diffuse and labile because glial VEGF immunoreactivity was greatly reduced if tissue sections were left in an aqueous medium overnight. We conclude that VEGF protein in normal female hippocampus is primarily nonneuronal rather than neuronal and suggest that glial VEGF immunoreactivity has been underestimated by past studies with other methods because there is a labile extracellular pool. We suggest that estrogens may exert actions on female hippocampal structure and function by increasing hippocampal VEGF.

Pre- and post-estrogen administration in global cerebral ischemia reduces blood-brain barrier breakdown in ovariectomized rats

“…However, estrogen treatment before and after ischemia-reperfusion following ovariectomy was seen to markedly restore the impairment to the BBB. In the same vein, previous studies demonstrated that estrogen treatment played a protective role against the hippocampus damage inflicted during global ischemia, and this result lends support to ours (4,12).…”

Acute restraint stress decreases c-fos immunoreactivity in hilar mossy cells of the adult dentate gyrus

“…2, 3) was labeled with a rhodamine-tagged antibody (Table 1) using methods described previously (Barouk et al 2011; Duffy et al 2013). Briefly, all sections were washed in 0.1 M phosphate buffer (PB) and blocked in 10% donkey serum (Sigma, St. Louis, MO) in 0.25% Triton and 0.005% BSA in 0.1 M PB for 1 h. The sections were then incubated in the goat polyclonal c-fos antibody (Table 1) and either the antibody to GluR2/3, GAD67, PV, NPY, calretinin, or nNOS (Table 1) in 1% donkey serum and 0.25% Triton X-100 in 0.1 M PB for 24 h. Following primary antibody incubation and 3 × 5 min washes in 0.1 M PB, sections were incubated for 2 h in the secondary antibodies (Table 1).…”

Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants

“…Notably, BDNF levels fluctuate with the estrous cycle and estrogen administration can increase the expression of BDNF in the PFC and hippocampus 63–66 . Dendrite complexity and spine synapse density also fluctuate with the ovarian cycle, and estrogen administration increases spine density in the hippocampus and PFC 67–69 .…”