SPARCL1 Promotes Excitatory But Not Inhibitory Synapse Formation and Function Independent of Neurexins and Neuroligins.

Emerging evidence supports roles for secreted extracellular matrix proteins in boosting synaptogenesis, synaptic transmission, and synaptic plasticity. SPARCL1 (also known as Hevin), a secreted non-neuronal protein, was reported to increase synaptogenesis by simultaneously binding to presynaptic neurexin-1α and to postsynaptic neuroligin-1B, thereby catalyzing formation of trans-synaptic neurexin/neuroligin complexes. However, neurexins and neuroligins do not themselves mediate synaptogenesis, raising the question of how SPARCL1 enhances synapse formation by binding to these molecules.

Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses.

Neuromodulators bind to pre- and postsynaptic G protein-coupled receptors (GPCRs), are able to quickly change intracellular cyclic AMP (cAMP) and Ca levels, and are thought to play important roles in neuropsychiatric and neurodegenerative diseases. Here, we discovered in human neurons an unanticipated presynaptic mechanism that acutely changes synaptic ultrastructure and regulates synaptic communication. Activation of neuromodulator receptors bidirectionally controlled synaptic vesicle numbers within nerve terminals.

Specific factors in blood from young but not old mice directly promote synapse formation and NMDA-receptor recruitment.

Aging drives a progressive decline in cognition and decreases synapse numbers and synaptic function in the brain, thereby increasing the risk for neurodegenerative disease. Pioneering studies showed that introduction of blood from young mice into aged mice reversed age-associated cognitive impairments and increased synaptic connectivity in brain, suggesting that young blood contains specific factors that remediate age-associated decreases in brain function. However, whether such factors in blood from young animals act directly on neurons to enhance synaptic connectivity, or whether they act by an indirect mechanism remains unknown.

Imaging organelle transport in primary hippocampal neurons treated with amyloid-β oligomers.

We describe a strategy for fluorescent imaging of organelle transport in primary hippocampal neurons treated with amyloid-β (Aβ) peptides that cause Alzheimer's disease (AD). This method enables careful, rigorous analyses of axonal transport defects, which are implicated in AD and other neurodegenerative diseases. Moreover, we present and emphasize guidelines for investigating Aβ-induced mechanisms of axonal transport disruption in the absence of nonspecific, irreversible cellular toxicity.

Dendritic and axonal mechanisms of Ca2+ elevation impair BDNF transport in Aβ oligomer-treated hippocampal neurons.

Disruption of fast axonal transport (FAT) and intracellular Ca(2+) dysregulation are early pathological events in Alzheimer's disease (AD). Amyloid-β oligomers (AβOs), a causative agent of AD, impair transport of BDNF independent of tau by nonexcitotoxic activation of calcineurin (CaN). Ca(2+)-dependent mechanisms that regulate the onset, severity, and spatiotemporal progression of BDNF transport defects from dendritic and axonal AβO binding sites are unknown.

Atlas stumbled: kinesin light chain-1 variant E triggers a vicious cycle of axonal transport disruption and amyloid-β generation in Alzheimer's disease.

Substantial evidence implicates fast axonal transport (FAT) defects in neurodegeneration. In Alzheimer's disease (AD), it is controversial whether transport defects cause or arise from amyloid-β (Aβ)-induced toxicity. Using a novel, unbiased genetic screen, Morihara et al.

Amyloid-β oligomers induce tau-independent disruption of BDNF axonal transport via calcineurin activation in cultured hippocampal neurons.

Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau.

Thyroid hormone accelerates opsin expression during early photoreceptor differentiation and induces opsin switching in differentiated TRα-expressing cones of the salmonid retina.

Thyroid hormone and its receptors (TRs) regulate photoreceptor differentiation and visual pigment protein (opsin) expression in the retinas of several vertebrates, including rodents and fish. In some of these animals, opsin expression can arise through switches within differentiated cone photoreceptors. In salmonid fishes, single cones express ultraviolet (SWS1) opsin during embryonic development and switch to blue (SWS2) opsin as the fishes grow.

Thyroid hormone induces a time-dependent opsin switch in the retina of salmonid fishes.

Purpose: To determine the role of thyroid hormone in inducing the UV (SWS1)-to-blue (SWS2) opsin switch in the retina of two salmonid fishes, the coho salmon (Oncorhynchus kisutch) and the rainbow trout (O. mykiss).

Methods: Fish were treated with thyroid hormone (T(4)) or the vehicle solution (0.

The ultraviolet opsin is the first opsin expressed during retinal development of salmonid fishes.

Purpose: To determine the spatial and temporal progression of opsin appearance during retinal development of salmonid fishes (genus Oncorhynchus and Salmo).

Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization with riboprobes against the five classes of opsins present in salmonids (UV, blue, green, red, and rhodopsin) were used to establish the sequence of opsin appearance and the localization of opsins to specific morphologic photoreceptor types.

Results: Both detection methods revealed that UV opsin mRNA was expressed first and was followed closely by red opsin mRNA.