PRG-1 transcriptional regulation independent from Nex1/Math2-mediated activation

Geist, Beate; Vorwerk, Brita; Coiro, Pierluca; Ninnemann, Olaf; Nitsch, Robert

doi:10.1007/s00018-011-0774-7

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…Primary hippocampal neurons were prepared from postnatal day 1 WT and KI pups according to previously described protocol with some minor modifications [41]. Briefly, mouse hippocampi were isolated and cells were cultured at a density of 50,000 cells/cm 2 on poly-D-lysine coated glass-bottom dishes (35 mm) using Neurobasal A medium supplemented with 2% B27, 0.5 mM glutamax and penicillin/streptomycin (10,000 U/ml).…”

Section: Mitochondrial Membrane Potentialmentioning

confidence: 99%

Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria

Berger

Stattmann

Cicvaric

et al. 2020

acta neuropathol commun

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Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of heme biosynthesis due to a pathogenic mutation in the Hmbs gene, resulting in half-normal activity of hydroxymethylbilane synthase. Factors that induce hepatic heme biosynthesis induce episodic attacks in heterozygous patients. The clinical presentation of acute attacks involves the signature neurovisceral pain and may include psychiatric symptoms. Here we used a knock-in mouse line that is biallelic for the Hmbs c.500G > A (p.R167Q) mutation with~5% of normal hydroxymethylbilane synthase activity to unravel the consequences of severe HMBS deficiency on affective behavior and brain physiology. Hmbs knock-in mice (KI mice) model the rare homozygous dominant form of AIP and were used as tool to elucidate the hitherto unknown pathophysiology of the behavioral manifestations of the disease and its neural underpinnings. Extensive behavioral analyses revealed a selective depression-like phenotype in Hmbs KI mice; transcriptomic and immunohistochemical analyses demonstrated aberrant myelination. The uncovered compromised mitochondrial function in the hippocampus of knock-in mice and its ensuing neurogenic and neuroplastic deficits lead us to propose a mechanistic role for disrupted mitochondrial energy production in the pathogenesis of the behavioral consequences of severe HMBS deficiency and its neuropathological sequelae in the brain.

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Section: Mitochondrial Membrane Potentialmentioning

confidence: 99%