Browsing by Subject "voltammetry"

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Open Access
An In Vivo Definition of Brain Histamine Dynamics Reveals Critical Neuromodulatory Roles for This Elusive Messenger.
(International journal of molecular sciences, 2022-11) Berger, Shane N; Baumberger, Beatrice; Samaranayake, Srimal; Hersey, Melinda; Mena, Sergio; Bain, Ian; Duncan, William; Reed, Michael C; Nijhout, H Frederik; Best, Janet; Hashemi, Parastoo
Histamine is well known for mediating peripheral inflammation; however, this amine is also found in high concentrations in the brain where its roles are much less known. In vivo chemical dynamics are difficult to measure, thus fundamental aspects of histamine's neurochemistry remain undefined. In this work, we undertake the first in-depth characterization of real time in vivo histamine dynamics using fast electrochemical tools. We find that histamine release is sensitive to pharmacological manipulation at the level of synthesis, packaging, autoreceptors and metabolism. We find two breakthrough aspects of histamine modulation. First, differences in H3 receptor regulation between sexes show that histamine release in female mice is much more tightly regulated than in male mice under H3 or inflammatory drug challenge. We hypothesize that this finding may contribute to hormone-mediated neuroprotection mechanisms in female mice. Second, a high dose of a commonly available antihistamine, the H1 receptor inverse agonist diphenhydramine, rapidly decreases serotonin levels. This finding highlights the sheer significance of pharmaceuticals on neuromodulation. Our study opens the path to better understanding and treating histamine related disorders of the brain (such as neuroinflammation), emphasizing that sex and modulation (of serotonin) are critical factors to consider when studying/designing new histamine targeting therapeutics.
Open Access
Serotonin is a Common Thread Linking Different Classes of Antidepressants.
(Res Sq, 2023-03-28) Witt, Colby E; Mena, Sergio; Holmes, Jordan; Hersey, Melinda; Buchanan, Anna Marie; Parke, Brenna; Saylor, Rachel; Honan, Lauren E; Berger, Shane N; Lumbreras, Sara; Nijhout, Frederik H; Reed, Michael C; Best, Janet; Fadel, James; Schloss, Patrick; Lau, Thorsten; Hashemi, Parastoo
Depression pathology remains elusive. The monoamine hypothesis has placed much focus on serotonin, but due to the variable clinical efficacy of monoamine reuptake inhibitors, the community is looking for alternative therapies such as ketamine (synaptic plasticity and neurogenesis theory of antidepressant action). There is evidence that different classes of antidepressants may affect serotonin levels; a notion we test here. We measure hippocampal serotonin in mice with voltammetry and study the effects of acute challenges of antidepressants. We find that pseudo-equivalent doses of these drugs similarly raise ambient serotonin levels, despite their differing pharmacodynamics because of differences in Uptake 1 and 2, rapid SERT trafficking and modulation of serotonin by histamine. These antidepressants have different pharmacodynamics but have strikingly similar effects on extracellular serotonin. Our findings suggest that serotonin is a common thread that links clinically effective antidepressants, synergizing different theories of depression (synaptic plasticity, neurogenesis and the monoamine hypothesis).