Targeting hippocampal amyloidogenesis with SV2A protein modulator levetiracetam.

Cerebral amyloid β (Aβ) proteostasis is compromised under neuronal overexcitation, long-term neuroinflammation and brain aging. Using the animal model of LPS-induced neuroinflammation we demonstrated that treatment with levetiracetam, a specific modulator of synaptic vesicle glycoprotein SV2A, rescues abnormal synaptic vesicle (SV) fusion and neurotransmitter release, decreasing elevated hippocampal APP levels in vivo. Therapy with levetiracetam upregulates the SV2A in hippocampus and restores the level of apolipoprotein E, involved in brain Aβ aggregation/clearance and resolution of inflammation.

The geometry of diphtheria toxoid CRM197 channel assessed by thiazolium salts and nonelectrolytes.

The geometry of the channel formed by nontoxic derivative of diphtheria toxin CRM197 in lipid bilayer was determined using the dependence of single-channel conductance upon the hydrodynamic radii of different nonelectrolytes. It was found that the cis entrance of CRM197 channel on the side of membrane to which the toxoid was added at pH 4.8 and the trans entrance on the opposite side at pH 6.

Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift.

Vitamin D is among the major neurosteroids whose role in developing and adult brain is intensively studied now. Its active form 1,25(OH)D regulates the expression and functioning of a range of brain-specific proteins, which orchestrate the neurotransmitter turnover, neurogenesis and neuroplasticity. Despite numerous studies of the vitamin D role in normal and pathological brain function, there is little evidence on the mechanisms of alterations in excitatory and inhibitory neurotransmission under vitamin D deficiency (VDD).

Modulation of neurosecretion and approaches for its multistep analysis.

Background: Neurosecretion is the multistep process occurring in separate spatial and temporal cellular boundaries which complicates its comprehensive analysis. Most of the research are focused on one distinct stage of synaptic vesicle recycling. Here, we describe approaches for complex analysis of synaptic vesicle (SV) endocytosis and separate steps of exocytosis at the level of presynaptic bouton and highly purified SVs.

The phenomenon of synaptic vesicle clustering as the prefusion state in the model system of exocytosis.

Our findings concern to the synaptic vesicle interactions that were reconstructed in the cell-free system and are thought to represent the different states of exocytosis pathway. The combination of different technical approaches allowed to study the features of aggregation and calcium-dependent homotypic fusion of synaptic vesicles. Electron microscopy observations of synaptic vesicle fraction purified from the rat brain showed the appearance of large particles formed by aggregated synaptic vesicles in the presence of the nerve terminal cytosolic proteins only.