Brain angiotensin II in dopaminergic imbalance-derived pathologies: neuroinflammation and vascular responses

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From: Neural Regeneration Research(Vol. 16, Issue 3)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 1,845 words
Lexile Measure: 1480L

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Byline: Victoria. Occhieppo, Osvaldo. Basmadjian, Claudia. Bregonzio

Brain angiotensin II (ANG II) as a pleiotropic player: Mental disorders have been commonly associated with an imbalance in many neurotransmitter systems, such as dopamine, glutamate, and gamma-aminobutyric acid. Considering the complexity of brain functioning, all components of the neurovascular unit should be considered in studies for a better comprehension of the physiopathology and possible therapeutics. ANG II is present in the brain and binds to AT[sub]1 receptors (AT[sub]1-R), located in the neurovascular unit and has a close relationship with the mentioned neurotransmitter systems. In pathological conditions, AT[sub]1-R expressed in astrocytes, microglia, and brain endothelial cells are key mediators in the development of an oxidative/inflammatory microenvironment, as well as in glial activation. Therefore, pharmacological intervention targeting AT[sub]1-R provides a holistic and moderated approach to modulate neurotransmission systems in addition to the glial and vascular responses [Figure 1]. This interaction is underscored by several studies that related brain ANG II to neurological disorders, such as Parkinson[acute accent]s disease (PD) and attention deficit hyperactivity disorder (ADHD).{Figure 1}

PD and brain ANG II: PD is the second most common neurodegenerative disorder, and the available therapies are only symptomatic. Current research are focused on elucidating the cause of dopaminergic cell death and developing treatment strategies that interfere with progression of the underlying neuropathology. The available evidence suggests that processes, such as oxidative stress, inflammation, mitochondrial dysfunction and excitotoxicity, are key players in the pathogenesis and progression of the disorder. Several findings have showed that microglial activation and/or nicotinamide adenine dinucleotide phosphate-oxidase derived superoxide participate in neurotoxin induced dopaminergic degeneration in different animal models of PD (Mertens et al., 2010). Moreover, it has been found that AT[sub]1-R overexpression and reduced insulin-like growth factor-1 availability are involved in neuroinflammatory processes, oxidative stress, microvascular rarefaction and dopaminergic neuronal degeneration. Particularly, AT[sub]1-R promote the initiation and progression of local neuroinflammation and oxidative stress under dopamine-imbalance conditions, as described in animal models of senescence and PD. Moreover, the interaction between brain ANG II and the central dopaminergic system is evident by the modulation of the dopamine release in striatum by AT[sub]1-R activation, since the acute administration of ANG II increases striatal dopamine release (Labandeira-Garcia et al., 2013; Perez-Lloret et al., 2017). It is important to highlight that AT[sub]1-R are present in the substantia nigra pars compacta and striatum of different mammals, including rats and humans (Perez-Lloret et al., 2017). Moreover, the density of AT[sub]1-R is higher in human striatum and substantia nigra compared to rats and other mammals. Interestingly, the density of AT[sub]1-R in the striatum is reduced in dopaminergic neurons of PD patients (Perez-Lloret et al., 2017).

Attention deficit hyperactive disorder and brain ANG II: The spontaneous hypertensive rats (SHR), a validated animal model of ADHD, exhibit AT[sub]1-R overexpression in brain microvessels...

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Gale Document Number: GALE|A636783713