Acute salt loading induces sympathetic nervous system overdrive in mice lacking salt-inducible kinase 1 (SIK1).

Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic high-salt intake in mice. Here, we further addressed the possible early mechanisms that may relate to the observed rise in BP in mice lacking SIK1. SIK1 knockout (sik1) and wild-type (sik1) littermate mice were challenged with either a high-salt (8% NaCl) or control (0.

GPER activation is effective in protecting against inflammation-induced nigral dopaminergic loss and motor function impairment.

Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects.

Role of Neurotrophic Factors in Parkinson's Disease.

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels.

GPER: A new tool to protect dopaminergic neurons?

Parkinson's disease (PD) is characterized by a selective degeneration of nigrostriatal dopaminergic pathway. Epidemiological studies revealed a male predominance of the disease that has been attributed to the female steroid hormones, mainly the estrogen. Estrogen neuroprotective effects have been shown in several studies, however the mechanisms responsible by these effects are still unclear.

Astrocyte-derived GDNF is a potent inhibitor of microglial activation.

Neuroinflammation is recognized as a major factor in Parkinson's disease (PD) pathogenesis and increasing evidence propose that microglia is the main source of inflammation contributing to the dopaminergic degeneration observed in PD. Several studies suggest that astrocytes could act as physiological regulators preventing excessive microglia responses. However, little is known regarding how astrocytes modulate microglial activation.