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Roles and functions of Atp6ap2 in the brain.

ABSTRACT: The classical renin-angiotensin system (RAS) in the body has been studied intensively in the last decades, since it is known that this system is involved in the regulation of blood pressure. Since nearly all members of the classical RAS have also been identified within the brain in the last decades and due to the existence of the blood-brain barrier, a RAS within the brain (bRAS) that is largely independent from the peripheral RAS has been postulated. All members of the angiotensin family as e.g., angiotensin II, angiotensin IV and angiotensin II (1-7) along with the respective receptors (e.g., angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), angiotensin IV receptor (AT4), angiotensin II (1-7) receptor (Mas)) have been identified within the brain. Moreover, a receptor capable of binding renin and the renin precursor prorenin with high affinity has also been detected within the brain. This protein functions as a membrane receptor for (pro)renin and also represents a V-ATPase subunit and is therefore termed (P)RR or Atp6ap2, respectively. In this review we shed light on the (known as well as putative) roles and functions of Atp6ap2 in the brain under physiological and pathophysiological conditions.

SUBMITTER: Bracke A

PROVIDER: S-EPMC6199949 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Roles and functions of Atp6ap2 in the brain.

Bracke Alexander A von Bohlen Und Halbach Oliver O

Neural regeneration research 20181201 12

The classical renin-angiotensin system (RAS) in the body has been studied intensively in the last decades, since it is known that this system is involved in the regulation of blood pressure. Since nearly all members of the classical RAS have also been identified within the brain in the last decades and due to the existence of the blood-brain barrier, a RAS within the brain (bRAS) that is largely independent from the peripheral RAS has been postulated. All members of the angiotensin family as e.g ...[more]

PMID: 30323117

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Project description:The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber-Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear. In the present study, we investigated whether and how Cbln1 signaling is involved in non-motor functions in adult mice. We show that acquisition and retention/retrieval of cued and contextual fear memory were impaired in Cbln1-null mice. In situ hybridization and immunohistochemical analyses revealed that Cbln1 is expressed in various extracerebellar regions, including the retrosplenial granular cortex and the hippocampus. In the hippocampus, Cbln1 immunoreactivity was present at the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare without overt mRNA expression, suggesting that Cbln1 is provided by perforant path fibers. Retention/retrieval, but not acquisition, of cued and contextual fear memory was impaired in forebrain-predominant Cbln1-null mice. Spatial learning in the radial arm water maze was also abrogated. In contrast, acquisition of fear memory was affected in cerebellum-predominant Cbln1-null mice. These results indicate that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially and that Cbln1 signaling likely regulates motor and non-motor functions in multiple brain regions.Significance statementDespites its well known role in motor coordination and motor learning, whether and how the cerebellum is involved in cognitive functions remains less clear. Cerebellin 1 (Cbln1) is highly expressed in the cerebellum and serves as an essential synaptic organizer. Although genes encoding Cbln1 and its receptor are associated with many psychiatric disorders, it remains unknown whether such cognitive impairments are caused by cerebellar dysfunction. Here, we show that Cbln1 is also expressed in the forebrain, including the hippocampus and retrosplenial granular cortex. Using forebrain- and cerebellum-predominant conditional Cbln1-null mice, we show that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially, indicating that Cbln1 signaling regulates both motor and non-motor functions in multiple brain regions.

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Roles and functions of Atp6ap2 in the brain.

Publications

Roles and functions of Atp6ap2 in the brain.

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