In neurons, intracellular membrane rafts are essential for specific actions of brain‐derived neurotrophic factor (
Zinc is important in neurogenesis, but excessive levels can cause apoptosis and other pathologies leading to cognitive impairments. Mast cells are present in many brain regions including the hippocampus, an area rich in vesicular zinc. Mast cells contain zinc‐rich granules and a well‐developed mechanism for uptake of zinc ions; both features point to the potential for a role in zinc homeostasis. Prior work using the Timm stain supported this hypothesis, as increased labile zinc was detected in the hippocampus of mast cell‐deficient mice compared to wild‐type mice while no differences in total zinc were found between the two genotypes in the whole brain or other tissues. The current report further examines differences in zinc homeostasis between wild‐type and mast cell‐deficient mice by exploring the zinc transporter ZnT3, which transports labile zinc into synaptic vesicles. The first study used immunocytochemistry to localize ZnT3 within the mossy fibre layer of the hippocampus to determine whether there was differential expression of ZnT3 in wild‐type versus mast cell‐deficient mice. The second study used inductively coupled plasma mass spectrometry (
- Award ID(s):
- 1749500
- PAR ID:
- 10457834
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- European Journal of Neuroscience
- Volume:
- 51
- Issue:
- 6
- ISSN:
- 0953-816X
- Page Range / eLocation ID:
- p. 1504-1513
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
Abstract BDNF ), which include the regulation of axon outgrowth, growth cone turning and synaptic transmission. Virtually, all the actions ofBDNF are mediated by binding to its receptor, TrkB. The association of TrkB with the tyrosine kinase, Fyn, is critical for its localization to intracellular membrane rafts. Here, we show that synapsins, a family of highly amphipathic neuronal phosphoproteins, regulate membrane raft lipid composition and consequently, the ability ofBDNF to regulate axon/neurite development and potentiate synaptic transmission. In the brains of mice lacking all synapsins, the expression of bothBDNF and TrkB were increased, suggesting thatBDNF /TrkB‐mediated signaling is impaired. Consistent with this finding, synapsin‐depleted neurons exhibit altered raft lipid composition, deficient targeting of Fyn to rafts, attenuated TrkB activation, and abrogation ofBDNF ‐stimulated axon outgrowth and synaptic potentiation. Conversely, overexpression of synapsins in neuroblastoma cells results in corresponding reciprocal changes in raft lipid composition, increased localization of Fyn to rafts and promotion ofBDNF ‐stimulated neurite formation. In the presence of synapsins, the ratio of cholesterol to estimated total phospholipids converged to 1, suggesting that synapsins act by regulating the ratio of lipids in intracellular membranes, thereby promoting lipid raft formation. These studies reveal a mechanistic link betweenBDNF and synapsins, impacting early development and synaptic transmission. -
Background Dysregulation of the corticotropin‐releasing factor (
CRF ) system has been observed in rodent models of binge drinking, with a large focus onCRF receptor 1 (CRF ‐R1). The role ofCRF ‐binding protein (CRF ‐BP ), a key regulator ofCRF activity, in binge drinking is less well understood. In humans, single‐nucleotide polymorphisms in are associated with alcohol use disorder and stress‐induced alcohol craving, suggesting a role forCRHBP CRF ‐BP in vulnerability to alcohol addiction.Methods The role and regulation of
CRF ‐BP in binge drinking were examined in mice exposed to the drinking in the dark (DID ) paradigm. Using in situ hybridization, the regulation ofCRF ‐BP ,CRF ‐R1, andCRF mRNA expression was determined in the stress and reward systems of C57BL /6J mice after repeated cycles ofDID . To determine the functional role ofCRF ‐BP in binge drinking,CRF ‐BP knockout (CRF ‐BP KO ) mice were exposed to 6 cycles ofDID , during which alcohol consumption was measured and compared to wild‐type mice.Results CRF ‐BP mRNA expression was significantly decreased in the prelimbic (PL ) and infralimbic medial prefrontal cortex (mPFC ) of C57BL /6J mice after 3 cycles and in thePL mPFC after 6 cycles ofDID . No significant changes inCRF orCRF ‐R1 mRNA levels were observed in mPFC , ventral tegmental area, bed nucleus of the stria terminalis, or amygdala after 3 cycles ofDID .CRF ‐BP KO mice do not show significant alterations in drinking compared to wild‐type mice across 6 cycles of DID.Conclusions These results reveal that repeated cycles of binge drinking alter
CRF ‐BP mRNA expression in the mPFC , a region responsible for executive function and regulation of emotion and behavior, including responses to stress. We observed a persistent decrease inCRF ‐BP mRNA expression in the mPFC after 3 and 6DID cycles, which may allow for increasedCRF signaling atCRF ‐R1 and contribute to excessive binge‐like ethanol consumption. -
Objective To elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis (
OA ).Methods Three‐month–old decorin‐null (Dcn−/−) and inducible decorin‐knockout (Dcni
KO ) mice were subjected to surgical destabilization of the medial meniscus (DMM ) to induce post‐traumaticOA . TheOA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG ) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy–nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro–computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild‐type and Dcn−/−mice were stimulated with the inflammatory cytokine interleukin‐1β (IL ‐1β) in vitro (n = 6 mice per group). The resulting chondrocyte response toIL ‐1β and release ofsGAG s were quantified.Results In both Dcn−/−and Dcni
KO mice, the absence of decorin resulted in acceleratedsGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn−/−mice developed more salient osteophytes, illustrating more severeOA . In cartilage explants treated withIL ‐1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion ofsGAG s was released to the media from Dcn−/−mouse explants, in both live and devitalized conditions (P < 0.05).Conclusion In post‐traumatic
OA , decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration. -
Abstract One in 26 people develop epilepsy and in these temporal lobe epilepsy (TLE) is common. Many patients display a pattern of neuron loss called hippocampal sclerosis. Seizures usually start in the hippocampus but underlying mechanisms remain unclear. One possibility is insufficient inhibition of dentate granule cells. Normally parvalbumin‐immunoreactive (PV) interneurons strongly inhibit granule cells. Humans with TLE display loss of PV interneurons in the dentate gyrus but questions persist. To address this, we evaluated PV interneuron and bouton numbers in California sea lions (
) that naturally develop TLE after exposure to domoic acid, a neurotoxin that enters the marine food chain during harmful algal blooms. Sclerotic hippocampi were identified by the loss of Nissl‐stained hilar neurons. Stereological methods were used to estimate the number of granule cells and PV interneurons per dentate gyrus. Sclerotic hippocampi contained fewer granule cells, fewer PV interneurons, and fewer PV synaptic boutons, and the ratio of granule cells to PV interneurons was higher than in controls. To test whether fewer boutons was attributable to loss versus reduced immunoreactivity, expression of synaptotagmin‐2 (syt2) was evaluated. Syt2 is also expressed in boutons of PV interneurons. Sclerotic hippocampi displayed proportional losses of syt2‐immunoreactive boutons, PV boutons, and granule cells. There was no significant difference in the average numbers of PV‐ or syt2‐positive boutons per granule cell between control and sclerotic hippocampi. These findings do not address functionality of surviving synapses but suggest reduced granule cell inhibition in TLE is not attributable to anatomical loss of PV boutons.Zalophus californianus -
Abstract Plant development requires communication on many levels, including between cells and between organelles within a cell. For example, mitochondria and plastids have been proposed to be sensors of environmental stress and to coordinate their responses. Here we present evidence for communication between mitochondria and chloroplasts during leaf and root development, based on genetic and physical interactions between three
M echanosensitive channel ofS mall conductance‐L ike (MSL ) proteins fromArabidopsis thaliana .MSL proteins areArabidopsis homologs of the bacterialM echanos ensitivec hannel ofS mall conductance (MscS), which relieves cellular osmotic pressure to protect against lysis during hypoosmotic shock.MSL 1 localizes to the inner mitochondrial membrane, whileMSL 2 andMSL 3 localize to the inner plastid membrane and are required to maintain plastid osmotic homeostasis during normal growth and development. In this study, we characterized the phenotypic effect of a genetic lesion in , both in wild type and inMSL 1msl2 msl3 mutant backgrounds.msl1 single mutants appear wild type for all phenotypes examined. The characteristic leaf rumpling inmsl2 msl3 double mutants was exacerbated in themsl1 msl2 msl3 triple mutant. However, the introduction of themsl1 lesion into themsl2 msl3 mutant background suppressed othermsl2 msl3 mutant phenotypes, including ectopic callus formation, accumulation of superoxide and hydrogen peroxide in the shoot apical meristem, decreased root length, and reduced number of lateral roots. All these phenotypes could be recovered by molecular complementation with a transgene containing a wild type version of . In yeast‐based interaction studies,MSL 1MSL 1 interacted with itself, but not withMSL 2 orMSL 3. These results establish that the abnormalities observed inmsl2 msl3 double mutants is partially dependent on the presence of functionalMSL 1 and suggest a possible role for communication between plastid and mitochondria in seedling development.