Ferric carboxymaltose-induced hypophosphatemia in the Axenfeld-Reiger syndrome.

We present a 45-year-old woman with complex gastrointestinal anatomy leading to short gut syndrome and chronic diarrhea who was admitted with symptomatic severe hypophosphatemia attributed to renal phosphate wasting induced by intravenous iron preparation ferric carboxymaltose. She was maintained on intravenous phosphate replacements. The treatment course was complicated by respiratory illness leading to volume depletion, acute kidney injury, and phosphate nephropathy. She developed chronic kidney disease and underwent kidney transplant. Our case report aims to increase awareness of hypophosphatemia related to ferric carboxymaltose.

Optogenetic induction of orbitostriatal long-term potentiation in the dorsomedial striatum elicits a persistent reduction of alcohol-seeking behavior in rats.

Uncontrolled drug-seeking and -taking behaviors are generally driven by maladaptive corticostriatal synaptic plasticity. The orbital frontal cortex (OFC) and its projections to the dorsomedial striatum (DMS) have been extensively implicated in drug-seeking and relapse behaviors. The influence of the synaptic plasticity of OFC projections to the DMS (OFC→DMS) on drug-seeking and -taking behaviors has not been fully characterized. To investigate this, we trained rats to self-administer 20% alcohol and then delivered an in vivo optogenetic protocol designed to induce long-term potentiation (LTP) selectively at OFC→DMS synapses. We selected LTP induction because we found that voluntary alcohol self-administration suppressed OFC→DMS transmission and LTP may normalize this transmission, consequently reducing alcohol-seeking behavior. Importantly, ex vivo slice electrophysiology studies confirmed that this in vivo optical stimulation protocol resulted in a significant increase in excitatory OFC→DMS transmission strength on day two after stimulation, suggesting that LTP was induced in vivo. Rat alcohol-seeking and -taking behaviors were significantly reduced on days 1-3, but not on days 7-11, after LTP induction. Striatal synaptic plasticity is modulated by several critical neurotransmitter receptors, including dopamine D1 receptors (D1Rs) and adenosine A2A receptors (A2ARs). We found that delivery of in vivo optical stimulation in the presence of a D1R antagonist abolished the LTP-associated decrease in alcohol-seeking behavior, whereas delivery in the presence of an A2AR antagonist may facilitate this LTP-induced behavioral change. These results demonstrate that alcohol-seeking behavior was negatively regulated by the potentiation of excitatory OFC→DMS neurotransmission. Our findings provide direct evidence that the OFC exerts "top-down" control of alcohol-seeking behavior via the DMS.

Prenatal Exposure to Alcohol Induces Functional and Structural Plasticity in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum.

BACKGROUND: Prenatal alcohol exposure (PAE) is a leading cause of hyperactivity in children. Excitation of dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the dorsomedial striatum (DMS), a brain region that controls voluntary behavior, is known to induce hyperactivity in mice. We therefore hypothesized that PAE-linked hyperactivity was due to persistently altered glutamatergic activity in DMS D1-MSNs. METHODS: Female Ai14 tdTomato reporter mice were given access to alcohol in an intermittent access, 2-bottle choice paradigm before pregnancy, and following mating with male D1-Cre mice, through the pregnancy period, and until postnatal day (P) 10. Locomotor activity was tested in juvenile (P21) and adult (P133) offspring, and alcohol-conditioned place preference (CPP) was measured in adult offspring. Glutamatergic activity in DMS D1-MSNs of adult PAE and control mice was measured by slice electrophysiology, followed by measurements of dendritic morphology. RESULTS: Our voluntary maternal alcohol consumption model resulted in increased locomotor activity in juvenile PAE mice, and this hyperactivity was maintained into adulthood. Furthermore, PAE resulted in a higher alcohol-induced CPP in adult offspring. Glutamatergic activity onto DMS D1-MSNs was also enhanced by PAE. Finally, PAE increased dendritic complexity in DMS D1-MSNs in adult offspring. CONCLUSIONS: Our model of PAE does result in persistent hyperactivity in offspring. In adult PAE offspring, hyperactivity is accompanied by potentiated glutamatergic strength and afferent connectivity in DMS D1-MSNs, an outcome that is also consistent with the observed increase in alcohol preference in PAE offspring. Consequently, a PAE-sensitive circuit, centered within the D1-MSN, may be linked to behavioral outcomes of PAE.