Reduction of BDNF results in GABAergic neuroplasticity dysfunction and contributes to late-life anxiety disorder.

The GABAergic neuroplasticity dysfunction (GND) has been proposed as a distinct pathology for late-life anxiety disorder (LLAD). Brain-derived neurotrophic factor (BDNF) is a critical signaling molecule that regulates the GABAergic neuroplasticity. This research was designed to explore our hypothesis that the reduction of BDNF along with aging could induce GND, which might contribute to LLAD, and application of exogenous BDNF might reverse LLAD by restoring the GABAergic neuroplasticity. We focused on the hippocampus because it is the neural core of mood regulation and can be affected by aging. Compared to young mice, BDNF messenger RNA (mRNA) and protein levels and those core neuroplasticity factors (neurotransmitter γ-aminobutyric acid [GABA] level, GABAA-R α2 and α5 subunits expression and GABA+ neurons) in hippocampus markedly decreased with anxiety-like behavior in aged mice. Knocking down BDNF mRNA in aged mice resulted in further dysfunction of GABAergic neuroplasticity and higher anxiety phenotype. Inversely, chronic exogenous BDNF treatment attenuated anxiety-like behavior, improved the cognitive function, and increased the neuroplasticity factors. We demonstrated that the basic function of BDNF in hippocampus was negatively correlated with GND and anxiety-like behavior of aged mice. These results provided evidence of a causal relationship between the reduced BDNF function in hippocampus and the anxiety susceptibility of aged mice. Gene knockdown mice model indicates the mechanism of low BDNF function in LLAD, particularly affecting GABA neurons, therefore bridging the neurotrophic factor and GABAergic neuroplasticity hypotheses of LLAD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Phenolic Components of Gastrodia elata improve Prognosis in Rats after Cerebral Ischemia/Reperfusion by Enhancing the Endogenous Antioxidant Mechanisms.

Pharmacological or spontaneous thrombolysis in ischemic stroke triggers an outbreak of reactive oxygen species and results in neuron death. Nrf2-mediated antioxidation in cells has been proved as a pivotal target for neuroprotection. This research reports that phenolic components of Gastrodia elata Blume (PCGE), a traditional Chinese medicine, can alleviate the pathological lesions in the penumbra and hippocampus by increasing the survival of neurons and astrocytes and improve neurofunction and cognition after reperfusion in a rat model of middle cerebral artery occlusion. LDH assay indicated that pretreatment of cells with PCGE (25 µg/ml) for 24 h significantly reduced H2O2-induced cell death in astrocytes and SH-SY5Y cells. Western blot showed that the nucleus accumulation of Nrf2 and the expression of cellular HO-1 and NQO-1, two of Nrf2 downstream proteins, were increased in both cells. BDNF, an Nrf2-dependent neurotrophic factor, was also upregulated by PCGE in astrocytes. These results illustrated that PCGE can reduce the cerebral ischemia/reperfusion injury and improve prognosis by remedying the cell damage within affected tissues. The protective effects of PCGE seem to be via activation of a Nrf2-mediated cellular defense system. Therefore, PCGE could be a therapeutic candidate for ischemic stroke and other oxidative stress associated neurological disorders.