Biology subjects

Gonzalez-Menendez, I.

Publications and source records attributed to Gonzalez-Menendez, I..

3 recordsLinked to original sources

bioRxiv2023

Active Suppression of the Nigrostriatal Pathway during Optogenetic Stimulation Revealed by Simultaneous fPET/fMRI

The dopaminergic system is a central component of the brains neurobiological framework, governing motor control, reward responses, and playing an essential role in various brain disorders such as Parkinsons disease and schizophrenia. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine transmission from the substantia nigra to the striatum, a connection that is vital to understanding many of the disease-related dysfunctions. However, stand-alone functional magnetic resonance imaging (fMRI) is unable to study the intricate interplay between brain activation and its molecular underpinnings. In our study, the simultaneous use of [18F]FDG functional positron emission tomography (fPET)/BOLD-fMRI provided a new insight that allowed us to demonstrate an active suppression of the nigrostriatal activity during optogenetic stimulation via presynaptic autoinhibition. Our in vivo observation emphasizes that the observed BOLD signal depression during neuronal stimulation does not correlate with neuronal inactivity, but results from an active suppression of neuronal firing as shown by the high [18F]FDG signal increase. This result not only illustrates the potential of simultaneous fPET/fMRI to understand the molecular mechanisms of brain function but also provides a new perspective on how neurotransmitters such as dopamine influence hemodynamic responses in the brain.

neuroscience↗

bioRxiv2023

Development of an optimized, non-stem cell line for intranasal delivery of therapeutic cargo to the central nervous system

Neural stem cells (NSC) are considered to be valuable candidates for delivering a variety of anti-cancer agents to brain tumors, including oncolytic viruses. However, owing to the previously reported tumorigenic potential of NSC cell line after intranasal administration (INA), here we identified the human hepatic stellate cell line (LX-2) as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAV) as therapeutic cargo, and being non-tumorigenic after INA. Our data show that LX-2 cells can longer withstand the OAV XVir-N-31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX-2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic HSV-TK integration into LX-2 leading to the high vulnerability to Ganciclovir. Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno-compromised mice 3 months after INA of LX-2 cells. Our data suggest that LX-2 is a novel robust and safe cell line for delivering anti-cancer and other therapeutic agents to the brain.

molecular biology↗

bioRxiv2023

Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis

Diet-induced body weight gain is a growing health problem worldwide, leading to several serious systemic diseases such as diabetes. Because it is often accompanied by a low-grade metabolic inflammation that alters systemic function, dietary changes may also contribute to the progression of neurodegenerative diseases. Here we demonstrate disrupted glucose and fatty acid metabolism and a disrupted plasma metabolome in a mouse model of Alzheimers disease following a western diet using a multimodal imaging approach and NMR-based metabolomics. We did not detect glial-dependent neuroinflammation, however using flow cytometry we observed T cell recruitment in the brains of western diet-fed mice. Our study highlights the role of the brain-liver-fat-axis and the adaptive immune system in the disruption of brain homeostasis due to a Western diet.

immunology↗