scholarly journals A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2691
Author(s):  
Vincenza D’Angelo ◽  
Mauro Giorgi ◽  
Emanuela Paldino ◽  
Silvia Cardarelli ◽  
Francesca R. Fusco ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Western Blotting ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Entopeduncular Nucleus ◽  
Knock Out ◽  
A2a Receptors ◽  
Cholinergic Interneurons ◽  
Knock Out Mice

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/− knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. The co-localization of A2A was studied in striatal cholinergic interneurons identified by anti-choline-acetyltransferase (ChAT) antibody. A2A mRNA and cyclic adenosine monophosphate (cAMP) contents were also assessed. In Tor1a+/+, Western blotting detected an A2A 45 kDa band, which was stronger in the striatum and the globus pallidus than in the entopeduncular nucleus. Moreover, in Tor1a+/+, immunofluorescence showed A2A roundish aggregates, 0.3–0.4 μm in diameter, denser in the neuropil of the striatum and the globus pallidus than in the entopeduncular nucleus. In Tor1a+/−, A2A Western blotting expression and immunofluorescence aggregates appeared either increased in the striatum and the globus pallidus, or reduced in the entopeduncular nucleus. Moreover, in Tor1a+/−, A2A aggregates appeared increased in number on ChAT positive interneurons compared to Tor1a+/+. Finally, in Tor1a+/−, an increased content of cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the globus pallidus. In Tor1a+/−, opposite changes of A2A receptors’ expression in the striatal-pallidal complex and the entopeduncular nucleus suggest that the pathophysiology of dystonia is critically dependent on a composite functional imbalance of the indirect over the direct pathway in basal ganglia.

scholarly journals Endocannabinoids and Dopamine Balance Basal Ganglia Output

2021 ◽  
Vol 15 ◽  
Author(s):  
Lilach Gorodetski ◽  
Yocheved Loewenstern ◽  
Anna Faynveitz ◽  
Izhar Bar-Gad ◽  
Kim T. Blackwell ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Control Unit ◽  
Vital Role ◽  
Primary Afferents ◽  
Entopeduncular Nucleus ◽  
Indirect Pathway ◽  
Relay Nucleus ◽  
Prevailing View

The entopeduncular nucleus is one of the basal ganglia's output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the Striatum and the globus pallidus, together with glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all these primary afferents to the entopeduncular nucleus. Our results suggest that the interplay between dopamine and endocannabinoids determines the balance between direct pathway (striatum) and indirect pathway (globus pallidus) in entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoid diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.

scholarly journals Antiwrinkle and Antimelanogenesis Effects of Tyndallized Lactobacillus acidophilus KCCM12625P

2020 ◽  
Vol 21 (5) ◽  
pp. 1620 ◽  
Author(s):  
Hye Yeon Lim ◽  
Deok Jeong ◽  
Sang Hee Park ◽  
Kon Kuk Shin ◽  
Yo Han Hong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Lactobacillus Acidophilus ◽  
Cyclic Adenosine Monophosphate ◽  
Probiotic Strain ◽  
Adenosine Monophosphate ◽  
Human Keratinocytes ◽  
Subsequent Treatment ◽  
Dermal Fibroblasts

UVB irradiation can induce generation of reactive oxygen species (ROS) that cause skin aging or pigmentation. Lactobacillus acidophilus is a well-known probiotic strain that regulates skin health through antimicrobial peptides and organic products produced by metabolism and through immune responses. In this study, we investigated the antioxidative, antiwrinkle, and antimelanogenesis effects of tyndallized Lactobacillus acidophilus KCCM12625P (AL). To analyze the effects of AL on UV irradiation-induced skin wrinkle formation in vitro, human keratinocytes and human dermal fibroblasts were exposed to UVB. Subsequent treatment with AL induced antiwrinkle effects by regulating wrinkle-related genes such as matrix metalloproteinases (MMPs), SIRT-1, and type 1 procollagen (COL1AL). In addition, Western blotting assays confirmed that regulation of MMPs by AL in keratinocytes was due to regulation of the AP-1 signaling pathway. Furthermore, we confirmed the ability of AL to regulate melanogenesis in B16F10 murine melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH). In particular, AL reduced the mRNA expression of melanogenesis-related genes such as tyrosinase, TYRP-1, and TYRP-2. Finally, we used Western blotting assays to confirm that the antimelanogenesis role of AL was due to its regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway. Collectively, these results indicate that AL has an antiwrinkle activity in damaged skin and can inhibit melanogenesis. Thus, AL should be considered an important substance for potential use in anti-aging drugs or cosmetics.

scholarly journals Dopamine D2Rs Coordinate Cue-Evoked Changes in Striatal Acetylcholine Levels

2021 ◽  
Author(s):  
Kelly M. Martyniuk ◽  
Arturo Torres-Herraez ◽  
Marcelo Rubinstein ◽  
Marie A. Labouesse ◽  
Christoph Kellendonk
Keyword(s):  
Temporal Correlation ◽  
General Mechanism ◽  
Neuron Activity ◽  
Knock Out ◽  
Cholinergic Interneurons ◽  
Motivated Behavior ◽  
Mutual Regulation ◽  
Knock Out Mice

AbstractIn the striatum, acetylcholine (ACh) neuron activity is modulated co-incident with dopamine (DA) release in response to unpredicted rewards and reward predicting cues and both neuromodulators are thought to regulate each other. While this co-regulation has been studied using stimulation studies, the existence of this mutual regulation in vivo during natural behavior is still largely unexplored. One long-standing controversy has been whether striatal DA is responsible for the induction of the cholinergic pause or whether D2R modulate a pause that is induced by other mechanisms. Here, we used genetically encoded sensors in combination with pharmacological and genetic inactivation of D2Rs from cholinergic interneurons (CINs) to simultaneously measure ACh and DA levels after CIN D2R inactivation. We found that CIN D2Rs are not necessary for the induction of cue induced dips in ACh levels but regulate dip lengths and rebound ACh levels. Importantly, D2R inactivation strongly decreased the temporal correlation between DA and Ach signals not only at cue presentation but also during the intertrial interval. This points to a general mechanism by which D2Rs coordinate both signals. At the behavioral level D2R antagonism increased the latency to lever press, which was not observed in CIN-selective D2R knock out mice. This latency correlated with the cue evoked dip length supporting a role of the ACh dip and it’s regulation by D2Rs in motivated behavior. Overall, our data indicate that striatal DA coordinate phasic ACh and DA signals via CIN D2Rs which is important for the regulation of motivated behavior.

Increased glyoxalase-1 levels in Fkbp5 knock-out mice caused by Glo1 gene duplication

2013 ◽  
Vol 46 (06) ◽  
Author(s):  
LK Kollmannsberger ◽  
NC Gassen ◽  
A Bultmann ◽  
J Hartmann ◽  
P Weber ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Knock Out ◽  
Glyoxalase 1 ◽  
Knock Out Mice

Functional characterization of the H+/K+ ATPase in wild type and gastrin knock-out mice

2007 ◽  
Vol 45 (05) ◽  
Author(s):  
A Schnur ◽  
P Hegyi ◽  
V Venglovecz ◽  
Z Rakonczay ◽  
I Ignáth ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Wild Type ◽  
Knock Out ◽  
Knock Out Mice
Sign in / Sign up

Export Citation Format

Share Document