Increase in activin A may counteract decline in synaptic plasticity with age.

Activin A, a member of the transforming growth factor β (TGF-β) family, is widely recognized for its neurotrophic and neuroprotective function in the developing and injured brain, respectively. Moreover, in the healthy adult brain, activin A has been shown to tune signal processing at excitatory synapses in a fashion that improves cognitive performance. Because its level in human cerebrospinal fluid rises with age, we wondered whether activin A has a role in mitigating the gradual cognitive decline that healthy individuals experience in late-life.

Tonic activin signaling shapes cellular and synaptic properties of CA1 neurons mainly in dorsal hippocampus.

Dorsal and ventral hippocampus serve different functions in cognition and affective behavior, but the underpinnings of this diversity at the cellular and synaptic level are not well understood. We found that the basal level of activin A, a member of the TGF-β family, which regulates hippocampal circuits in a behaviorally relevant fashion, is much higher in dorsal than in ventral hippocampus. Using transgenic mice with a forebrain-specific disruption of activin receptor signaling, we identified the pronounced dorsal-ventral gradient of activin A as a major factor determining the distinct neurophysiologic signatures of dorsal and ventral hippocampus, ranging from pyramidal cell firing, tuning of frequency-dependent synaptic facilitation, to long-term potentiation (LTP), long-term depression (LTD), and de-potentiation.

Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.

Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types.

Network Reconstruction as a Novel High-Level Marker of Functional Neuronal Viability.

Neuronal viability is essential for the maintenance of neuronal networks. Already slight noxious modifications, for example, the selective interruption of interneurons' function, which enhances the excitatory drive inside a network, may already be harmful for the overall network. To monitor neuronal viability on the network level, we implemented a network reconstruction approach that infers the effective connectivity of cultured neurons from live-cell fluorescence microscopy recordings.

Glial Glutamate Transporter-Mediated Plasticity: System x/xCT/SLC7A11 and EAAT1/2 in Brain Diseases.

Glial cells play an essential role in the complex function of the nervous system. In particular, astrocytes provide nutritive support for neuronal cells and are involved in regulating synaptic transmission. Oligodendrocytes ensheath axons and support information transfer over long distances.

Environmental enrichment recruits activin A to recalibrate neural activity in mouse hippocampus.

The TGF-β family member activin A modulates neural underpinnings of cognitive and affective functions in an activity-dependent fashion. We have previously shown that exploration of a novel and enriched environment (EE) strongly enhanced activin signaling. Whereas the many beneficial effects of EE are amply documented, the underlying mechanisms remain largely elusive.

Common network effect-patterns after monoamine reuptake inhibition in dissociated hippocampus cultures.

The pharmacological treatment of major depressive disorder with currently available antidepressant drugs is still unsatisfying as response to medication is delayed and in some patients even non-existent. To understand complex psychiatric diseases such as major depressive disorder and their treatment, research focus is shifting from investigating single neurons towards a view of the entire functional and effective neuronal network, because alterations on single synapses through antidepressant drugs may translate to alterations in the entire network. Here, we examined the effects of monoamine reuptake inhibitors on in vitro hippocampal network dynamics using calcium fluorescence imaging and analyzing the data with means of graph theoretical parameters.

Synaptic Vesicle Pool Monitoring with Synapto-pHluorin.

Synaptic vesicle exocytosis can be monitored with genetically encoded pH sensors in an in vitro fluorescence microscopy setup. Here, we describe a workflow starting with preparation of a primary cell culture to eventually estimate synaptic vesicle pool sizes based on electrical current-evoked vesicle release, which is reported by the synaptobrevin 2-EGFP fusion protein synapto-pHluorin (spH) that is expressed inside the synaptic vesicle membrane. The readily releasable pool and the recycling pool of synaptic vesicles are released separately in response to electrical stimulation.

Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction.

Glioblastoma represents the most devastating form of human brain cancer, associated with a very poor survival rate of patients. Unfortunately, treatment options are currently limited and the gold standard pharmacological treatment with the chemotherapeutic drug temozolomide only slightly increases the survival rate. Experimental studies have shown that the efficiency of temozolomide can be improved by inducing ferroptosis - a recently discovered form of cell death, which is different from apoptosis, necrosis, or necroptosis and, which is characterized by lipid peroxidation and reactive oxygen species accumulation.

Rewiring of neuronal networks during synaptic silencing.

Analyzing the connectivity of neuronal networks, based on functional brain imaging data, has yielded new insight into brain circuitry, bringing functional and effective networks into the focus of interest for understanding complex neurological and psychiatric disorders. However, the analysis of network changes, based on the activity of individual neurons, is hindered by the lack of suitable meaningful and reproducible methodologies. Here, we used calcium imaging, statistical spike time analysis and a powerful classification model to reconstruct effective networks of primary rat hippocampal neurons in vitro.

Chemotherapeutic xCT inhibitors sorafenib and erastin unraveled with the synaptic optogenetic function analysis tool.

In the search for new potential chemotherapeutics, the compounds' toxicity to healthy cells is an important factor. The brain with its functional units, the neurons, is especially endangered during the radio- and chemotherapeutic treatment of brain tumors. The effect of the potential compounds not only on neuronal survival but also neuronal function needs to be taken into account.