The Effect of TGF-β1 Reduced Functionality on the Expression of Selected Synaptic Proteins and Electrophysiological Parameters: Implications of Changes Observed in Acute Hepatic Encephalopathy.

Abstract

Decreased platelet count represents a feature of acute liver failure (ALF) pathogenesis. Platelets are the reservoir of transforming growth factor 1 (TGF-β1), a multipotent cytokine involved in the maintenance of, i.a., central nervous system homeostasis. Here, we analyzed the effect of a decrease in TGF-β1 active form on synaptic proteins levels, and brain electrophysiology, in mice after intraperitoneal (ip) administration of TGF-β1 antibody (anti-TGF-β1; 1 mg/mL). Next, we correlated it with a thrombocytopenia-induced TGF-β1 decrease, documented in an azoxymethane-induced (AOM; 100 mM ip) model of ALF, and clarified the impact of TGF-β1 decrease on blood-brain barrier functionality. The increase of both synaptophysin and synaptotagmin in the cytosolic fraction, and its reduction in a membrane fraction, were confirmed in the AOM mice brains. Both proteins' decrease in analyzed fractions occurred in anti-TGF-β1 mice. In turn, an increase in postsynaptic (NR1 subunit of N-methyl-D-aspartate receptor, postsynaptic density protein 95, gephyrin) proteins in the AOM brain cortex, but a selective compensatory increase of NR1 subunit in anti-TGF-β mice, was observed. The alterations of synaptic proteins levels were not translated on electrophysiological parameters in the anti-TGF-β1 model. The results suggest the impairment of synaptic vesicles docking to the postsynaptic membrane in the AOM model. Nevertheless, changes in synaptic protein level in the anti-TGF-β1 mice do not affect neurotransmission and may not contribute to neurologic deficits in AOM mice.

• Authors: Mariusz Popek, Bartosz Bobula, Karolina Orzeł-Gajowik, Magdalena Zielińska
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 3 (Jan 19 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35163004 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Synaptophysin
• Syp protein, mouse
• Tgfb1 protein, mouse
• Transforming Growth Factor beta1
• Synaptotagmins
• Azoxymethane

Topics

• Animals
• Antibodies (administration & dosage, pharmacology)
• Azoxymethane (adverse effects)
• Blood-Brain Barrier (metabolism)
• Brain (physiopathology)
• Cell Line
• Disease Models, Animal
• Down-Regulation
• Electrophysiological Phenomena
• Hepatic Encephalopathy (chemically induced, metabolism, physiopathology)
• Injections, Intraperitoneal
• Liver Failure, Acute (chemically induced, metabolism, physiopathology)
• Male
• Mice
• Rats
• Synaptophysin (metabolism)
• Synaptotagmins (metabolism)
• Transforming Growth Factor beta1 (metabolism)