Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

Abstract

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease.

Pseudane-VII Regulates LPS-Induced Neuroinflammation in Brain Microglia Cells through the Inhibition of iNOS Expression

“…We found that the anti-neuroinflammatory effects of pseudane-VII primarily involve the ERK1/2 pathway. Our results show that pseudane-VII has anti-neuroinflammatory efficacy through the inhibition of ERK1/2 phosphorylation, however, according to reports of Kawakowsky et al, ERK phosphorylation is beneficial to Alzheimer’s disease because it can induces neuronal survival and cognition [28,29]. Moreover, studies by Jahrlin et al, show that pERK is important for memory formation because the formation of PPARγ on the pERK protein complex is essential for memory formation [30].…”

Sex- and age-related changes in GABA signaling components in the human cortex

“…In neurodegenerative disorders like Alzheimer’s disease, sex difference has been well documented. The mechanisms underlying AD are not well understood, but aging is considered to be the leading risk factor for the disease [60–62, 110, 122–124]. Sex- and age-specific changes in key molecular components of the major transmitter systems, as described in this study, could account for the effects of sex and age on the disease, or they might be factors that influence disease prevalence and progression.…”

“…Sex and age bias has been observed in many neurological disorders such as Alzheimer’s disease and depression disorder [5, 59–63] and has also been linked to the GABAergic system [6, 27, 60, 64, 65]. Therefore, a thorough investigation is required to identify the link between sex and age and the GABAergic changes observed in these and other neurological conditions.…”

Alzheimer’s Disease – Estrogens and Selective Estrogen Receptor Modulators, Friends or Foes?

“…Non-classical intracellular signaling associated with estrogen called ANGELS (activator of non-genomic estrogen-like signaling) might have a neuroprotective effect. Estrene, an estrogen derivative, causes a recovery of the losses in cortical cholinergic projections to the basal forebrain and an attenuation of learning deficit in a model of AD in mice obtained by injecting fragments of Aβ1-42 (47).…”