A Risk Factor for Attention Deficit Hyperactivity Disorder Induces Marked Long-Term Anatomical Changes at GABAergic-Dopaminergic Synapses in the Rat Ventral Tegmental Area.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive/impulsive presentation of ADHD.

Anterior thalamic nuclei neurons sustain memory.

A hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated with examples of clinical amnesia.

A schizophrenia risk factor induces marked anatomical deficits at GABAergic-dopaminergic synapses in the rat ventral tegmental area: Essential evidence for new targeted therapies.

To develop new therapies for schizophrenia, evidence accumulated over decades highlights the essential need to investigate the GABAergic synapses that presynaptically influence midbrain dopaminergic neurons. Since current technology restricts these studies to animals, and evidence accumulated in recent decades indicates a developmental origin of schizophrenia, we investigated synaptic changes in male rat offspring exposed to maternal immune activation (MIA), a schizophrenia risk factor. Using a novel combination of lentiviruses, peroxidase-immunogold double labeling, three-dimensional serial section transmission electron microscopy and stereology, we observed clear anatomical alterations in synaptic inputs on dopaminergic neurons in the midbrain posterior ventral tegmental area (pVTA).

A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis.

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years.

An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease.

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders. In addition to the accumulation of auto-fluorescent storage material in lysosomes, NCLs are largely characterised by region-specific neuroinflammation that can predict neuron loss. These phenotypes suggest alterations in the extracellular environment-making the secretome an area of significant interest.

Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease.

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are neurodegenerative lysosomal storage diseases predominantly affecting children. Single administration of brain-directed lentiviral or recombinant single-stranded adeno-associated virus 9 (ssAAV9) vectors expressing ovine CLN5 into six pre-clinically affected sheep with a naturally occurring CLN5 NCL resulted in long-term disease attenuation. Treatment efficacy was demonstrated by non-invasive longitudinal in vivo monitoring developed to align with assessments used in human medicine.

Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to the neurotoxicity of accumulated Αβ, sAPPα has many neuroprotective and neurotrophic properties.

RNA-Sequencing Analysis Reveals a Regulatory Role for Transcription Factor in the Mature Motor Cortex.

() encodes a transcription factor essential for the specification of layer 5 projection neurons (PNs) in the developing cerebral cortex. As with many developmental transcription factors, continues to be expressed into adulthood, suggesting it remains crucial to the maintenance of neuronal phenotypes. Despite the continued expression, a function has yet to be explored for in the PNs of the developed cortex.

Characterisation of early changes in ovine CLN5 and CLN6 Batten disease neural cultures for the rapid screening of therapeutics.

Batten disease (neuronal ceroid lipofuscinosis) refers to a group of neurodegenerative lysosomal storage diseases predominantly affecting children. There are currently no effective treatments, and the functions of many of the associated gene products are unknown. Here we characterise fetal neural cultures from two genetically distinct sheep forms of Batten disease, with mutations in the lysosomal protein encoding gene CLN5 and endoplasmic reticulum membrane protein encoding gene CLN6, respectively.

Fezf2 expression in layer 5 projection neurons of mature mouse motor cortex.

The mature cerebral cortex contains a wide diversity of neuron phenotypes. This diversity is specified during development by neuron-specific expression of key transcription factors, some of which are retained for the life of the animal. One of these key developmental transcription factors that is also retained in the adult is Fezf2, but the neuron types expressing it in the mature cortex are unknown.

Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord.

Lentiviral vectors have proved an effective method to deliver transgenes into the brain; however, they are often hampered by a lack of spread from the site of injection. Modifying the viral envelope with a portion of a rabies envelope glycoprotein can enhance spread in the brain by using long-range axon projections to facilitate retrograde transport. In this study, we generated two chimeric envelopes containing the extra-virion and transmembrane domain of rabies SADB19 or CVS-N2c with the intra-virion domain of vesicular stomatitis virus.

Prevalence of child sexual abuse among adolescents in Geneva: results of a cross sectional survey.

Objective: To measure the cumulative prevalence of child sexual abuse in a representative sample of the adolescent population of Geneva.

Design: Cross sectional survey with an anonymous self administered questionnaire centred on a factual description of sexual activities.

Setting: 68 classes (17 schools) randomly selected from the 201 ninth grade classes of the public school system in Geneva.