KLC4 shapes axon arbors during development and mediates adult behavior.

Development of elaborate and polarized neuronal morphology requires precisely regulated transport of cellular cargos by motor proteins such as kinesin-1. Kinesin-1 has numerous cellular cargos which must be delivered to unique neuronal compartments. The process by which this motor selectively transports and delivers cargo to regulate neuronal morphogenesis is poorly understood, although the cargo-binding kinesin light chain (KLC) subunits contribute to specificity. Our work implicates one such subunit, KLC4, as an essential regulator of axon branching and arborization pattern of sensory neurons during development. Using live imaging approaches in klc4 mutant zebrafish, we show that KLC4 is required for stabilization of nascent axon branches, proper microtubule (MT) dynamics, and endosomal transport. Furthermore, KLC4 is required for proper tiling of peripheral axon arbors: in klc4 mutants, peripheral axons showed abnormal fasciculation, a behavior characteristic of central axons. This result suggests that KLC4 patterns axonal compartments and helps establish molecular differences between central and peripheral axons. Finally, we find that klc4 mutant larva are hypersensitive to touch and adults show anxiety-like behavior in a novel tank test, implicating klc4 as a new gene involved in stress response circuits.

Lateral Hypothalamic Mc3R-Expressing Neurons Modulate Locomotor Activity, Energy Expenditure, and Adiposity in Male Mice.

The central melanocortin system plays a crucial role in the control of energy balance. Although the decreased energy expenditure and increased adiposity of melanocortin-3 receptor (Mc3R)-null mice suggest the importance of Mc3R-regulated neurons in energy homeostasis, the roles for specific subsets of Mc3R neurons in energy balance have yet to be determined. Because the lateral hypothalamic area (LHA) contributes to the control of energy expenditure and feeding, we generated Mc3rcre mice to determine the roles of LHA Mc3R (Mc3RLHA) neurons in energy homeostasis. We found that Mc3RLHA neurons overlap extensively with LHA neuron markers that contribute to the control of energy balance (neurotensin, galanin, and leptin receptor) and project to brain areas involved in the control of feeding, locomotion, and energy expenditure, consistent with potential roles for Mc3RLHA neurons in these processes. Indeed, selective chemogenetic activation of Mc3RLHA neurons increased locomotor activity and augmented refeeding after a fast. Although the ablation of Mc3RLHA neurons did not alter food intake, mice lacking Mc3RLHA neurons displayed decreased energy expenditure and locomotor activity, along with increased body mass and adiposity. Thus, Mc3R neurons lie within LHA neurocircuitry that modulates locomotor activity and energy expenditure and contribute to energy balance control.

Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus.

The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar extent as Sim1(PVH) neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1(PVH) neurons; their activation fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXT(PVH) neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1(PVH) neurons in feeding regulation.

AVP neurons in the paraventricular nucleus of the hypothalamus regulate feeding.

Melanocortins and their receptors are critical components of energy homeostasis and the paraventricular nucleus of the hypothalamus (PVH) is an important site of melanocortin action. Although best known for its role in osmoregulation, arginine vasopressin (AVP) has been implicated in feeding and is robustly expressed in the PVH. Since the anorectic melanocortin agonist MTII activates PVH-AVP neurons, we hypothesized that PVH-AVP neurons contribute to PVH-mediated anorexia. To test this, we used an AVP-specific Cre-driver mouse in combination with viral vectors to acutely manipulate PVH-AVP neuron function. Using designer receptors exclusively activated by designer drugs (DREADDs) to control PVH-AVP neuron activity, we show that activation of PVH-AVP neurons acutely inhibits food intake, whereas their inhibition partially reverses melanocortin-induced anorexia. We further show that MTII fails to fully suppress feeding in mice with virally-induced PVH-AVP neuron ablation. Thus PVH-AVP neurons contribute to feeding behaviors, including the acute anorectic response to MTII.

[Progressive paraparesis with sensorineural deafness and leukoencephalopathy revealing neurobrucellosis]. / Paraparésie et surdité progressives avec leuco-encéphalopathie révélant une neurobrucellose chronique.

INTRODUCTION: Brucellosis is a rare disease with variable neurological and imaging manifestations. CASE REPORT: A 54-year-old woman presented with progressive paraparesis and sensorineural hearing loss over 18 months. The presence of diffuse white matter changes on brain magnetic resonance imaging (MRI) and cerebrospinal fluid findings led to the diagnosis of neurobrucellosis. Spinal MRI did not show any lesion that could explain the paraparesis that was finally attributed to the leukoencephalopathic lesions. The patient improved clinically after three months of antibiotic treatment but no significant changes were noticed on brain imaging. DISCUSSION AND CONCLUSION: Neurobrucellosis is a treatable disease which should be discussed when a patient presents with the triade progressive paraparesis, sensorineural hearing loss and leukoencephalopathy on MRI. Outcome can be favorable if adapted treatment is given early.

[Brucellar meningitis complicated by aneurysmal subarachnoid hemorrhage]. / Méningite brucellienne compliquée d'hémorragie méningée par rupture d'anévrisme: rapport d'un cas et revue de la littérature.

INTRODUCTION: Brucellosis is a rare disease in which neurological complications, and more particularly, intracranial aneurysmal hemorrhages were rarely reported. CASE REPORT: A brucellar meningitis was diagnosed in a 29-year-old man, who had been suffering from an unusual headache for about two months. Three days after beginning treatment, the patient developed an intracranial right frontal hemorrhage that led to the discovery of a ruptured anterior communicating artery aneurysm. The aneurysm was clipped surgically and doxycycline and rifampin were given for three months. The outcome was excellent. DISCUSSION AND CONCLUSION: Clinical manifestations of brucellosis are variable. Neurovascular complications are rare and probably linked to delay in diagnosis of CNS invasion or inadequate initial treatment. Appropriate and prompt medical, and if necessary, surgical management can lead to excellent outcome.

[Miliary tuberculosis and intramedullary tuberculoma of the conus medullaris]. / Tuberculose miliaire et tuberculome intramédullaire du cône terminal.

INTRODUCTION: This case is presented to illustrate the diagnostic and therapeutic dilemmas of a rare condition: intramedullary tuberculoma of the conus medullaris. OBSERVATION: A 49 year-old man was admitted in April 2005 for pain, paresthesias and weakness of lower limbs evolving for about 15 days. He had also unusual tiredness with mild fever and dry cough for more than a month. Chest x-ray then computed tomography suggested miliary tuberculosis and spinal MR showed a conus medullaris ring enhancing lesion suggestive of tuberculoma. Lumbar puncture or surgical biopsy was not performed. He responded well to a combination of four antituberculous drugs, with progressive clinical and radiological improvement. CONCLUSION: Although it is a very rare condition, conus terminalis tuberculoma can be suspected in the presence of typical MR image and clinical context. Treatment is primarily medical. Surgery is indicated only in case of rapid neurological deterioration or doubts about diagnosis.

[Rapid sensory motor neuropathy after gastric restriction surgery]. / Polyneuropathie axonale sensitivo-motrice rapide après chirurgie de restriction gastrique.

INTRODUCTION: Central and peripheral neurological complications have been described in association with bariatric surgery over the last 20 years. CASE REPORT: A 40 year-old women developed a sensory motor neuropathy 3 months after a gastric restriction operation followed by a 30 kilograms weight loss. No specific vitamin or mineral deficiency was detected but she improved after multivitamin and minerals supplementation. CONCLUSION: Acute or subacute neuropathy may develop in 1 to 2p.cent of patients who undergo bariatric surgery. Its pathogenesis is not very clear but the most commonly associated factors are rapid weight loss and non-supplementation with vitamins and minerals post-operatively.