Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra

Singh, Maibam; Vı́gh, József; Amberg, Gregory C.

doi:10.1523/eneuro.0090-21.2021

Cited by 9 publications

(4 citation statements)

References 62 publications

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“…Whether, this network effect depends on a different AT1R distribution among different types of neurons is not clear at present. In general, our data support the notion that Ang II substantially modulates the activity of inhibitory neurons (Yao et al, 2008;Legat et al, 2019;Singh et al, 2021). With respect to the observed effect of Ang II on the respiratory rhythm, we assume that an increase in the number and/or firing rate of tonically active excitatory neurons is involved in the increase of the overall drive of the network (Kam et al, 2013), while a temporal well-coordinated phasic inhibition of excitatory neurons by rhythmic glycinergic neurons might increase the "respiratory" burstfrequency by, e.g., shortening the refractory period (Cregg et al, 2017;Baertsch et al, 2018).…”

Section: Type Of Neurons Involved In Ang II Responsesupporting

confidence: 89%

Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling

Tacke

Bischoff²,

Harb³

et al. 2023

Front. Cell. Neurosci.

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Angiotensin II (Ang II) is the primary modulator of the renin-angiotensin system and has been widely studied for its effect on the cardiovascular system. While a few studies have also indicated an involvement of Ang II in the regulation of breathing, very little is known in this regard and its effect on brainstem respiratory regions such as the preBötzinger complex (preBötC), the kernel for inspiratory rhythm generation, has not been investigated yet. This study reports that Ang II temporarily increases phrenic nerve activity in the working heart-brainstem preparation, indicating higher central respiratory drive. Previous studies have shown that the carotid body is involved in mediating this effect and we revealed that the preBötC also plays a part, using acute slices of the brainstem. It appears that Ang II is increasing the respiratory drive in an AT1R-dependent manner by optimizing the interaction of inhibitory and excitatory neurons of the preBötC. Thus, Ang II-mediated effects on the preBötC are potentially involved in dysregulating breathing in patients with acute lung injury.

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Section: Type Of Neurons Involved In Ang II Responsesupporting

confidence: 89%

Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling

Tacke

Bischoff²,

Harb³

et al. 2023

Front. Cell. Neurosci.

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“…This was speculated to be because these peptides, along with Ang 1‐7, can influence the firing rates of neurons (Albrecht et al, 2000; Ambühl et al, 1994; Barnes et al, 1990). Ang II is now established to modulate GABAergic neurotransmission, with direct effects on dopaminergic neuronal activity (Singh et al, 2021).…”

Section: The Physiological Roles and Therapeutic Potential Of Ace And...mentioning

confidence: 99%

Angiotensin‐converting enzymes as druggable features of psychiatric and neurodegenerative disorders

Santiago

Parra

Nani

et al. 2023

Journal of Neurochemistry

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The renin‐angiotensin system (RAS) plays essential roles in maintaining peripheral cardiovascular homeostasis, with its potential roles in the brain only being recognized more recently. Angiotensin‐I‐converting enzyme (ACE) is the main component of the RAS, and it has been implicated in various disorders of the brain. ACE and other RAS components, including the related enzyme ACE2, angiotensin peptides and their respective receptors, can participate in the pathological state, as well as with potential to contribute to neuroprotection and/or to complement existing treatments for psychiatric illness. In this narrative review, we aimed to identify the main studies describing the functions of the RAS and ACEs in the brain and their association with brain disorders. These include neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. We also discuss the possible association of a functional polymorphism of the ACE gene with these brain diseases and the relevance of the neuroprotective and anti‐inflammatory properties of ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Based on this, we conclude that there is significant potential value to the inclusion of ACEis and/or ARBs as a novel integrated approach for the treatment of various disorders of the brain, and particularly for psychiatric illness.

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“…They act by antagonizing the angiotensin II (AT 1 ) receptor. It happens that this receptor, expressed in neurons, is a potential target of neurodegenerative diseases [83][84][85][86][87][88][89][90][91][92]. Animal models of neurodegenerative diseases have been instrumental in demonstrating that candesartan can cross the blood-brain barrier and act on receptors expressed in neural cells.…”

Section: Is It Good To Have Chronic Low Blood Pressure?mentioning

confidence: 99%

Can chronic therapeutic drug use by the elderly affect Alzheimer’s disease risk and rate of progression?

Franco

Serrano-Marín

2023

Explor Neuroprot Ther

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There is no approved drug capable of halting the progression of the most prevalent neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD). Current therapeutic strategies focus mainly on the inhibition of the formation of protein aggregates and their deposition in the central nervous system. However, after almost a hundred years, proper management of the disease is still lacking. The fact of not finding effective management tools in the various clinical trials already carried out suggests that new hypotheses and strategies should be explored. Although vast resources have been allocated to the investigation of protein aggregates and the pathophysiology is now better understood, clues to the actual etiology are lacking. It is well known that brain homeostasis is of paramount importance for the survival of neurons. Drugs that target the periphery are often not subject to evaluation for their potential effect on the central nervous system. While acute treatments may be irrelevant, pills used for chronic conditions can be detrimental to neurons, especially in terms of progressive damage leading to a long-term decline in neuronal survival. Due to the lack of advances in the search for a curative treatment for neurodegenerative diseases, and the lack of new hypotheses about their etiology, a novel hypothesis is here proposed. It consists of assuming that the effects of the drugs most commonly used by the elderly, such as antihypertensive, hypoglycemic, and hypocholesterolemic, could have a negative impact on neuronal survival.

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Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra

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Cited by 9 publications

References 62 publications

Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling

Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling

Angiotensin‐converting enzymes as druggable features of psychiatric and neurodegenerative disorders

Can chronic therapeutic drug use by the elderly affect Alzheimer’s disease risk and rate of progression?

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