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Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation. The mechanism underlying caffeine consumption inversely correlation with depression is unclear. Here, authors identified adenosine A2A receptor in the lateral septum mediating depressive symptoms via direct outputs to the habenula and the hypothalamus. [ABSTRACT FROM AUTHOR]

The distribution and function of P2X and P2Y receptor subtypes were investigated on intact or cultured intramural ganglia of the cat urinary bladder by immunocytochemistry and calcium-imaging techniques, respectively. Neurons were labeled by all seven P2X receptor subtype antibodies and antibodies for P2[Y.sub.2], P2[Y.sub.4], P2[Y.sub.6] and P2[Y.sub.12 ]receptor subtypes with a staining intensity of immunoreactivity in the following order: P2[X.sub.3]=P2[Y.sub.2]= P2[Y.sub.4]=P2[Y.sup.6]=P2[Y.sub.12], =P2[X.sub.1]>P2[X.sub.2]=P2[X.sub.2]=P2[X.sub.4]>P2[X.sub.5] =P2[X.sub.6]=P2[X.sub.7]. P2[Y.sub.1] receptor antibodies labeled glial cells, but not neurons. P2[X.sub.3] and P2[Y.sup.4] polyclonal antibodies labeled--95 and 40% of neurons, respectively. Double staining showed that 100, 48.8, and 97.4% of P2[X.sup.3] receptor-positive neurons coexpressed choline acetyl transferase (CHAT), nitric oxide synthase (NOS), and neurofilament 200 (NF200), respectively, whereas 100, 59.2, and 97.6% of P2[Y.sub.4] receptor-positive neurons coexpressed ChAT, NOS, and NF200, respectively. Application of ATP, [alpha],[beta]-methylene ATP, and uridine triphosphate elevated intracellular [Ca.sup.2+] concentration in a subpopulation of dissociated cultured cat intramural ganglia neurons, demonstrating the presence of functional P2[Y.sup.4] and P2[X.sup.3] receptors. This study indicates that P2X and P2Y receptor subtypes are expressed by cholinergic parasympathetic neurons innervating the urinary bladder. The neurons were also stained for NF200, usually regarded as a marker for large sensory neurons. These novel histochemical properties of cholinergic neurons in the cat bladder suggest that the parasympathetic pathways to the cat bladder may be modulated by complex purinergic synaptic mechanisms. ATP; intramural ganglia

Objective: To assess the effect of serine protein inhibitor A3N (serpinA3N) in ischemic stroke and to explore its mechanism of action. Methods: Mouse ischemic stroke model was induced by transient middle cerebral artery occlusion followed by reperfusion. The expression pattern of serpinA3N was assessed using immunofluorescence, Western blot analysis, and real‐time quantitative PCR. An adeno‐associated virus (AAV) and recombinant serpinA3N were administered. Additionally, co‐immunoprecipitation‐mass spectrometry and immunofluorescence co‐staining were used to identify protein interactions. Results: SerpinA3N was upregulated in astrocytes and neurons within the ischemic penumbra after stroke in the acute phase. The expression of serpinA3N gradually increased 6 h after reperfusion, peaked on the day 2–3, and then decreased by day 7. Overexpression of serpinA3N by AAV significantly reduced the infarct size and improved motor function, associated with alleviated inflammation and oxidative stress. SerpinA3N treatment also reduced apoptosis both in vivo and in vitro. Co‐immunoprecipitation‐mass spectrometry and Western blotting revealed that clusterin interacts with serpinA3N, and Akt‐mTOR pathway members were upregulated by serpinA3N both in vivo and in vitro. Conclusions: SerpinA3N is expressed in astrocytes and penumbra neurons after stroke in mice. It reduces brain damage possibly via interacting with clusterin and inhibiting neuronal apoptosis and neuroinflammation. [ABSTRACT FROM AUTHOR]