Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

Du, Jianyang; Reznikov, Leah R.; Welsh, Michael J.

doi:10.1371/journal.pone.0115310

Cited by 11 publications

(8 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B and C). The expression of ASIC4 in the pituitary gland but not the TG or DRG agreed with previous reports from human (Grunder et al ., ), rat (Akopian et al ., ) and mouse (Du et al ., ) samples. In the CNS, X‐gal‐positive signals were detected in many regions, including the olfactory bulb, cortex, hippocampus, amygdala, thalamus, hypothalamus, cerebellum and spinal cord but not adult DRG (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety

Lin

Chien

Chiang

et al. 2015

Eur J of Neuroscience

View full text Add to dashboard Cite

Although ASIC4 is a member of the acid-sensing ion channel (ASIC) family, we have limited knowledge of its expression and physiological function in vivo. To trace the expression of this ion channel, we generated the ASIC4-knockout/CreERT(2)-knockin (Asic4(Cre) (ERT) (2)) mouse line. After tamoxifen induction in the Asic4(Cre) (ERT)(2)::CAG-STOP(floxed)-Td-tomato double transgenic mice, we mapped the expression of ASIC4 at the cellular level in the central nervous system (CNS). ASIC4 was expressed in many brain regions, including the olfactory bulb, cerebral cortex, striatum, hippocampus, amygdala, thalamus, hypothalamus, brain stem, cerebellum, spinal cord and pituitary gland. Colocalisation studies further revealed that ASIC4 was expressed mainly in three types of cells in the CNS: (i) calretinin (CR)-positive and/or vasoactive intestine peptide (VIP)-positive interneurons; (ii) neural/glial antigen 2 (NG2)-positive glia, also known as oligodendrocyte precursor cells; and (iii) cerebellar granule cells. To probe the possible role of ASIC4, we hypothesised that ASIC4 could modulate the membrane expression of ASIC1a and thus ASIC1a signaling in vivo. We conducted behavioral phenotyping of Asic4(Cre) (ERT)(2) mice by screening many of the known behavioral phenotypes found in Asic1a knockouts and found ASIC4 not involved in shock-evoked fear learning and memory, seizure termination or psychostimulant-induced locomotion/rewarding effects. In contrast, ASIC4 might play an important role in modulating the innate fear response to predator odor and anxious state because ASIC4-mutant mice showed increased freezing response to 2,4,5-trimethylthiazoline and elevated anxiety-like behavior in both the open-field and elevated-plus maze. ASIC4 may modulate fear and anxiety by counteracting ASIC1a activity in the brain.

show abstract

Section: Resultsmentioning

confidence: 99%

Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety

Lin

Chien

Chiang

et al. 2015

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…ASIC1a is known to play an important role for sensing acidosis during ischemic stroke, seizure, fear, panic, and MS, as well as synaptic transmission 7 36 37 38 39 40 . A previous study also showed that blockade of ASIC1a activity would result in activation of the endogenous enkephalin pathway in the CNS and thus produce analgesia for neuropathic pain 41 .…”

Section: Discussionmentioning

confidence: 99%

Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis

Wang

Chung

Liao

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain. Elicited pain levels were as high in Asic1a−/−, Asic2−/− and Asic3−/− mice as wild-type mice even though only Asic1a−/− mice showed reduced EAE disease severity, which indicates that pain in EAE was independent of disease severity. We thus adopted an EAE model without pertussis toxin (EAEnp) to restrain activated immunity in the periphery and evaluate the PNS contribution to pain. Both EAE and EAEnp mice showed similar pain behaviors and peripheral neuropathy in nerve fibers and DRG neurons. Moreover, pregabalin significantly reduced neuropathic pain in both EAE and EAEnp mice. Our findings highlight the essential role of the PNS in neuropathic pain in EAE and pave the way for future development of analgesics without side effects in the CNS.

show abstract

“…Using probes that differentiated between ASIC1a and ASIC1b , it has been shown that whereas ASIC1a is expressed in rat DRG, spinal cord and brain, ASIC1b expression is restricted to the DRG [28]. However, reverse-transcriptase PCR (RT-PCR) analysis showed that ASIC1b , along with all other ASIC transcripts, is expressed in mouse anterior pituitary tissue [29] and rat trigeminal mesencephalic nucleus neurons [30], suggesting that ASIC1b is present in certain brain regions. A variety of techniques have been used to demonstrate that both ASIC2a and ASIC2b show diffuse expression throughout the brain in a number of species, as well as the spinal cord and DRG [26, 31–33].…”

Section: Introductionmentioning

confidence: 99%

Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat

Schuhmacher

Smith

2016

Mol Brain

View full text Add to dashboard Cite

Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

show abstract

Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

Cited by 11 publications

References 66 publications

Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety

Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety

Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis

Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat

Contact Info

Product

Resources

About