Synaptic Vesicle Precursors and Lysosomes Are Transported by Different Mechanisms in the Axon of Mammalian Neurons.

BORC is a multisubunit complex previously shown to promote coupling of mammalian lysosomes and C. elegans synaptic vesicle (SV) precursors (SVPs) to kinesins for anterograde transport of these organelles along microtubule tracks. We attempted to meld these observations into a unified model for axonal transport in mammalian neurons by testing two alternative hypotheses: (1) that SV and lysosomal proteins are co-transported within a single type of "lysosome-related vesicle" and (2) that SVPs and lysosomes are distinct organelles, but both depend on BORC for axonal transport. Analyses of various types of neurons from wild-type rats and mice, as well as from BORC-deficient mice, show that neither hypothesis is correct. We find that SVPs and lysosomes are transported separately, but only lysosomes depend on BORC for axonal transport in these neurons. These findings demonstrate that SVPs and lysosomes are distinct organelles that rely on different machineries for axonal transport in mammalian neurons.

A role for hippocampal adult neurogenesis in shifting attention toward novel stimuli.

New granule neurons are born in the dentate gyrus region of the hippocampus throughout life. Behavioral effects of slowing or stopping this ongoing neurogenesis are generally observed only in complex cognitive tasks involving high levels of cue or memory interference or in tests of emotion presented after stress exposure. Here, we tested the role of new neurons in naïve rats in a simple, one-trial orienting task previously shown to be affected by hippocampal lesions. Using a pharmacogenetic method to inhibit adult neurogenesis, we found that loss of new neurons decreased orienting toward a novel auditory cue. Rats lacking new neurons showed this change in orienting only when they were drinking from a water bottle and not when they were exploring an empty arena, suggesting that the deficit is not in the ability to orient to a novel sound but in shifting of attention toward a second stimulus. Orienting was reduced to the same extent after 4 or 8 weeks of neurogenesis reduction but was not detectably altered after 2 or 3 weeks of treatment, suggesting that new neurons must mature for approximately a month before functioning in this behavior. These findings demonstrate that adult-born neurons affect behavior in a simple attention reorienting task in naïve animals with no prior stress or task-related learning.

Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome.

The hereditary spastic paraplegias (HSP) are a clinically and genetically heterogeneous group of disorders characterized by progressive lower limb spasticity. Mutations in subunits of the heterotetrameric (ε-ß4-µ4-σ4) adaptor protein 4 (AP-4) complex cause an autosomal recessive form of complicated HSP referred to as "AP-4 deficiency syndrome". In addition to lower limb spasticity, this syndrome features intellectual disability, microcephaly, seizures, thin corpus callosum and upper limb spasticity. The pathogenetic mechanism, however, remains poorly understood. Here we report the characterization of a knockout (KO) mouse for the AP4E1 gene encoding the ε subunit of AP-4. We find that AP-4 ε KO mice exhibit a range of neurological phenotypes, including hindlimb clasping, decreased motor coordination and weak grip strength. In addition, AP-4 ε KO mice display a thin corpus callosum and axonal swellings in various areas of the brain and spinal cord. Immunohistochemical analyses show that the transmembrane autophagy-related protein 9A (ATG9A) is more concentrated in the trans-Golgi network (TGN) and depleted from the peripheral cytoplasm both in skin fibroblasts from patients with mutations in the µ4 subunit of AP-4 and in various neuronal types in AP-4 ε KO mice. ATG9A mislocalization is associated with increased tendency to accumulate mutant huntingtin (HTT) aggregates in the axons of AP-4 ε KO neurons. These findings indicate that the AP-4 ε KO mouse is a suitable animal model for AP-4 deficiency syndrome, and that defective mobilization of ATG9A from the TGN and impaired autophagic degradation of protein aggregates might contribute to neuroaxonal dystrophy in this disorder.

The Impact of Age and Cognitive Reserve on Resting-State Brain Connectivity.

Cognitive reserve (CR) is a protective mechanism that supports sustained cognitive function following damage to the physical brain associated with age, injury, or disease. The goal of the research was to identify relationships between age, CR, and brain connectivity. A sample of 90 cognitively normal adults, ages 45-64 years, had their resting-state brain activity recorded with electroencephalography (EEG) and completed a series of memory and executive function assessments. CR was estimated using years of education and verbal IQ scores. Participants were divided into younger and older age groups and low- and high-CR groups. We observed greater left- than right-hemisphere coherence in younger participants, and greater right- than left-hemisphere coherence in older participants. In addition, greater coherence was observed under eyes-closed than eyes-open recording conditions for both low-CR and high-CR participants, with a more substantial difference between recording conditions in individuals high in CR regardless of age. Finally, younger participants low in CR exhibited greater mean coherence than younger participants high in CR, whereas the opposite pattern was observed in older participants, with greater coherence in older participants high in CR. Together, these findings suggest the possibility of a shift in the relationship between CR and brain connectivity during aging.

Acute ligation of the radial and ulnar arteries: A case report and review of literature.

Isolated injury to the radial or ulnar artery results in no significant complications in patients who undergo repair or ligation of the injured artery. However, ligation of both infrabrachial vessels of the upper extremity is associated with limb loss from ischemia due to lack of collateral circulation. A rare case of acute ligation of both the radial and ulnar arteries in a drug abuser where collateral vessels preserved the circulation to the hand is reported.

Les blessures isolées de l'artère radiale ou de l'artère cubitale n'entraînent pas de complications importantes chez les patients qui subissent une réparation ou une ligature de l'artère lésée. Par contre, la ligature des deux vaisseaux sous-brachiaux du membre supérieur se solde par la perte de celui-ci en raison de l'ischémie causée par l'absence de circulation collatérale. Voici un cas rare de ligature des artères radiale et cubitale, réalisée en urgence chez un utilisateur de drogues chez qui la circulation sanguine dans la main a été assurée par les vaisseaux collatéraux.

Acute median nerve compression neuropathy from a foreign body in the forearm.

Acute compression of the median nerve in the forearm usually occurs from compartment syndrome. A case of acute compression neuropathy of the median nerve from a foreign body, where there was no evidence of compartment syndrome, is reported. The diagnosis was made from the patient's symptoms and radiographs. Early recognition and decompression of the forearm with removal of the foreign body led to full recovery.

D'ordinaire, la compression aiguë du nerf médian de l'avant-bras est causée par un syndrome de loge. Un cas de neuropathie de compression aiguë du nerf médian imputable à un corps étranger, sans trace de syndrome de loge, est décrit. Le diagnostic a été posé grâce aux symptômes du patient et à des radiographies. Un dépistage précoce et une décompression de l'avant-bras avec retrait du corps étranger ont permis un rétablissement total.