[smart (OP)]

Does chronic activation of the microglia by air pollution and particulate matter is harmful (neurotoxic) or beneficial (neurotrophic) to dopaminergic neurons?

[exothermic]

Does chronic activation of the microglia by air pollution and particulate matter is harmful (neurotoxic) or beneficial (neurotrophic) to dopaminergic neurons?

*harmful*

Reactive microgliosis is the microglial response to neuron damage. Chronic evironmental toxin exposure [provided there is sufficient exposure] would initiate a pro-neuroinflammatory response.

In short, this includes the alteration of microglial homeostasis and the resultant dysmorphic microglia patterns - thus adversely affecting the microenvironment of dopaminergic neurons.

[smart (OP)]

How MAC1 receptor regulate microglial internalization ?

[evan_au]

Is reactive microgliosis a beneficial or harmful process?

It is an immune response to a (perceived) threat to the brain.
- If it is an appropriate response to a genuine threat, then it is beneficial.
- If it is not a genuine threat, or if causes damage to non-threatened parts of the brain, then it can be harmful.
- Like all immune responses*, there is a fine line between doing too little, and doing too much.

*The same goes for military responses...

[smart (OP)]

It is an immune response to a (perceived) threat to the brain.
- If it is an appropriate response to a genuine threat, then it is beneficial.
- If it is not a genuine threat, or if causes damage to non-threatened parts of the brain, then it can be harmful.
- Like all immune responses*, there is a fine line between doing too little, and doing too much.

*The same goes for military responses...

Why is microglia-mediated neurotoxicity is implicated in the immune response to NP exposure? 

[exothermic]

- It is an immune response to a (perceived) threat to the brain.
- If it is not a genuine threat, or if causes damage to non-threatened parts of the brain, then it can be harmful.

In the context of what has been presented i.e. toxin exposure - reactive microgliosis would mediated exclusively via neuron damage due to the upregulation of proinflammatory target genes, cytokines, chemokines ect.

[smart (OP)]

In the context of what has been presented i.e. toxin exposure - reactive microgliosis would mediated exclusively via neuron damage due to the upregulation of proinflammatory target genes, cytokines, chemokines ect.

Precisely. Chronic neuroinflammation is a pathological evidence of microglial activation. Exposure to airborn toxins and nanomaterials can significantly affect the neuroimmune system; Ultrafine particles (PM2.5) can penetrate into the lungs and translocate into the brain via the blood-brain barrier, causing oxidative stress and proinflammatory response. 

[evan_au]

I was asked to clarify the following comments:

Like all immune responses, there is a fine line between doing too little, and doing too much.

An underactive immune response exposes the individual to a huge number of attacks from a range of external pathogens, with a severe impact on life expectancy and quality of life.
An overactive immune response exposes the individual to a huge number of attacks from a range of internal mechanisms, with a severe impact on life expectancy and quality of life.

So there is a fine line between doing too little and doing too much - and the optimum balance in one environment may be different from a different environment.

Then there is the crossover, where genuine disease is caused by a pathogen, and the immune system must protect against future infections, as well as recognize and eliminate the current infection. The killer T cells can destroy pathogens and human cells, whether infected or not. If they target the wrong type of cell, the immune system can cause a lot of collateral damage. The microglia in the brain target injured neurons.

I recall an example of this from many years ago, with the viral disease polio, which is controlled these days with a very safe and effective polio vaccine. In a percentage of infected individuals, polio virus infects the brain or spinal cord, causing severe paralysis, and sometimes death. An experimental study compared the damage done to mice with a normal immune system, and those with a suppressed immune system. In fact, it appeared that the damage to the brain and resulting paralysis was primarily caused by an overactive response from the body's own immune system.

This does not mean that we should just suppress the immune system, and invite chronic infection from many pathogens.
The optimum result for an individual may not be the same as the optimum response for a whole population.

The same goes for military responses...

An underactive police or military presence allows criminal, terrorist or invader activity to flourish, and the society descends into violence and chaos.

An overactive police or military presence attacks innocent sectors of the population, blocks healthy debate on social issues and the society descends into repression and chaos. There is a significant risk that such a nation will become an invader.

So there is a fine line between doing too little and doing too much - and the optimum balance in one environment may be different from a different environment.

The optimum result for an individual country may not be the same as the optimum response for the whole world.

With great power comes great responsibility.

The same could be said for cyber security.