Question

Regarding the cytotoxicity of inflammation, which statement is not correct? a. Both oxygen and nitrogen reactive species can participate in the deleterious effects of inflammation. b. Inactivation of NADPH-oxidase, but not of nitric oxide synthase matigates MPTP-induced neurodegeneration in mice. c. The detrimental effects of inflammation on dopaminergic neurons can be mediated by soluble factors. d. Astrocytes and microglial cells can mutually modulate their degree of activation. e. Dopaminergic neurons express receptors for various deleterious cytokines.

Short answer

a) Both oxygen and nitrogen reactive species can participate in the deleterious effects of inflammation. b) Inactivation of NADPH-oxidase, but not of nitric oxide synthase mitigates MPTP-induced neurodegeneration in mice. c) The detrimental effects of inflammation on dopaminergic neurons can be mediated by soluble factors. d) Astrocytes and microglial cells can mutually modulate their degree of activation. e) Dopaminergic neurons express receptors for various deleterious cytokines. Answer: b) Inactivation of NADPH-oxidase, but not of nitric oxide synthase mitigates MPTP-induced neurodegeneration in mice.

Step-by-step solution

Understand each statement

In this step, read all the statements carefully and ensure that you understand them. If necessary, you can further research certain terms or concepts that are not clear.

Evaluate statement a

Assess the correctness of statement a: "Both oxygen and nitrogen reactive species can participate in the deleterious effects of inflammation." This statement is correct. These reactive species can cause cellular damage during inflammation by attacking biomolecules such as lipids, proteins, and DNA.

Evaluate statement b

Assess the correctness of statement b: "Inactivation of NADPH-oxidase, but not of nitric oxide synthase mitigates MPTP-induced neurodegeneration in mice." This statement is not correct. Both the inactivation of NADPH-oxidase and nitric oxide synthase can help protect against MPTP-induced neurodegeneration. Nitric oxide synthase inhibition has been shown to provide neuroprotection in animal models of Parkinson's disease.

Evaluate statement c

Assess the correctness of statement c: "The detrimental effects of inflammation on dopaminergic neurons can be mediated by soluble factors." This statement is correct. Soluble factors such as cytokines, chemokines, and other inflammatory mediators can adversely affect dopaminergic neurons and contribute to neurodegeneration.

Evaluate statement d

Assess the correctness of statement d: "Astrocytes and microglial cells can mutually modulate their degree of activation." This statement is correct. These cell types interact with each other in the central nervous system and can influence each other's activation state, which can have implications for inflammation and neurodegeneration.

Evaluate statement e

Assess the correctness of statement e: "Dopaminergic neurons express receptors for various deleterious cytokines." This is correct. Expression of these receptors makes dopaminergic neurons more vulnerable to the harmful effects of inflammatory cytokines, which may contribute to the progression of neurodegenerative diseases.

Identify the incorrect statement

Based on the evaluation in the previous steps, the incorrect statement is b: "Inactivation of NADPH-oxidase, but not of nitric oxide synthase mitigates MPTP-induced neurodegeneration in mice."

Key concepts

Reactive Oxygen Species

Reactive Oxygen Species (ROS) are highly reactive molecules that play a significant role in cellular processes. They are derived from oxygen and include free radicals like superoxide and hydroxyl radicals, as well as non-radical molecules like hydrogen peroxide.
In the context of inflammation, these reactive species can cause damage to cells by attacking essential biomolecules.

• They can target lipids, leading to membrane damage.
• Proteins can be oxidized, losing their functionality.
• DNA damage may occur, potentially leading to mutations or cell death.

The body, aware of ROS's potential hazard, has defensive mechanisms in place. Antioxidants and enzymes such as superoxide dismutase aim to neutralize these harmful agents. However, when the production of ROS exceeds the body's ability to manage them, oxidative stress takes place, contributing to inflammation and diseases like neurodegeneration.

Neurodegeneration

Neurodegeneration refers to the progressive loss of structure or function of neurons, including death of neurons. It’s a hallmark of various neurological disorders such as Alzheimer's and Parkinson's diseases.
A constant state of inflammation in the nervous system can exacerbate neuronal damage. Chronic production of inflammatory mediators, like cytokines, can lead to harmful changes:

• Increased oxidative stress, which harms neurons.
• Release of cytotoxic factors damaging neuronal networks.
• Impairment of normal cellular functions, disrupting neuronal signaling.

Inflammation-driven neurodegeneration often involves both astrocytes and microglial activation, leading to an environment detrimental to neuronal survival. Understanding these processes is key in developing therapies to mitigate or slow the progression of neurodegenerative diseases.

Astrocytes and Microglia

Astrocytes and Microglia are crucial glial cells in the central nervous system (CNS) that play pivotal roles in maintaining homeostasis.
Astrocytes support neurons by providing nutrients, maintaining the blood-brain barrier, and modulating neurotransmitter systems. In response to CNS damage, they become reactive, a process known as astrogliosis, and can secrete inflammatory cytokines.
Microglia are the resident immune cells of the CNS, constantly surveying the environment for signs of injury or infection. Upon activation, they can phagocytize debris and release both pro- and anti-inflammatory factors.
When both cell types are activated, they interact closely.

• This bidirectional communication can amplify or suppress inflammatory responses.
• They can influence each other's activation states, impacting the overall inflammatory milieu.

Astrocytes and microglia's ability to modulate their activity is crucial in inflammation and neurodegeneration, highlighting the importance of these cells in maintaining CNS integrity.

Dopaminergic Neurons

Dopaminergic Neurons are specialized neurons responsible for producing dopamine, a critical neurotransmitter involved in reward, motivation, and motor control. They are primarily located in brain regions such as the substantia nigra.
These neurons are particularly vulnerable to oxidative stress and inflammation:

• They express receptors for various pro-inflammatory cytokines.
• This expression makes them susceptible to damage from inflammatory signals.
• Environmental toxins and genetic factors can exacerbate their vulnerability.

Damage or death of dopaminergic neurons is a hallmark of Parkinson’s disease, resulting in movement disorders due to impaired dopamine levels. Understanding how inflammation and oxidative stress impact these neurons can help develop protective strategies against such neurodegenerative conditions.