How Zika virus induces congenital microcephaly

Epidemiological studies show that in utero fetal infection with the Zika virus (ZIKV) may lead to microcephaly, an irreversible congenital malformation of the brain characterized by an incomplete development of the cerebral cortex. However, the mechanism of Zika virus-associated microcephaly remains unclear.

Combined analysis of human fetuses infected with Zika virus, cultures of human neuronal stem cells and mice embryos showed that ZIKV infection of cortical progenitors -stem cells for cortical neurons) controlling neurogenesis triggers stress in the endoplasmic reticulum -where some of the cellular proteins and lipids are synthesized in the embryonic brain, inducing signals in response to incorrect protein conformation.

When it reaches the brain, Zika virus infects neuronal stem cells, which will generate fewer neurons, and by inducing chronic stress in the endoplasmic reticulum, it promotes apoptosis-the early death of these neuronal cells. These two combined mechanisms explain why the cerebral cortex of infected fetuses becomes deficient in neurons and is therefore smaller in size.

 Researchers administered an inhibitors of protein-folding re-sponse in cortical progenitors and found that this inhibited the development of microcephaly in mice embryos infected with Zika virus. The defects observed are specific to an infection by ZIKV, as other neurotropical viruses of the flavivirus family- West Nile virus and yellow fever did not cause microcephaly, in contrast to Zika virus.
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New molecules may prevent stroke and neurodegenerative diseases

Researchers have discovered a new class of molecules in the brain that synchronize cell-to-cell communication and immune activity in response to injury or diseases. Elovanoids ELVs are bioactive chemical messengers made from omega-3 very long chain polyunsaturated fatty acids VLC-PUFAs,n-3. They are released on demand when cells are damaged or stressed.

Working in neuronal cell cultures from the cerebral cortex and from the hippocampus and a model of ischemic stroke, the researchers found that elovanoids not only protected neuronal cells and promoted their survival, but maintained their integrity and stability.

This can proffer solution in the understanding of how the complexity and resiliency of the brain are sustained when confronted with adversities such as stroke, Parkinson's or Alzheimer's and neuroprotection signaling needs to be activated and how neurons communicate among themselves.

These novel molecules participate in communicating messages to overall synaptic organization to ensure an accurate flow of information through neuronal circuits. We know how neurons make synaptic connections with other neurons, however these connections have to be malleable to change strength appropriately.

Elovanoids might play a central role as synaptic organizers, especially important in conditions resulting from synaptic dysfunction such as autism or amyotropic lateral sclerosis, for which there is no therapeutic solutions.

The researchers discovered the structure and characteristics of two elovanoids - ELV-N32 and ELV-N34 - in the brain. Starting with neuron cell cultures and then an experimental model of stroke, they found that elovanoids were activated when cells underwent either oxygen deprivation or excitotoxicity - early events associated with stroke, epilepsy, Parkinson's, traumatic brain injury and other neurodegenerative diseases.

They determined the concentrations and therapeutic windows at which elovanoids conferred neuroprotection. They discovered that elovanoids overcame the damaging effects and toxicity of these early events. In the stroke model, elovanoids reduced the size of the damaged brain area, initiated repair mechanisms and improved neurological recovery.
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