The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain.

NLGN4X was identified as a single causative gene of rare familial nonsyndromic autism for the first time. It encodes the postsynaptic membrane protein Neuroligin4 (NLGN4), the functions and roles of which, however, are not fully understood due to the lack of a closely homologous gene in rodents. It has been confirmed only recently that human NLGN4 is abundantly expressed in the cerebral cortex and is localized mainly to excitatory synapses. However, the detailed histological distribution of NLGN4, which may have important implications regarding the relationships between NLGN4 and autistic phenotypes, has not been clarified. In this study, we raised specific monoclonal and polyclonal antibodies against NLGN4 and examined the distribution of NLGN4 in developing and developed human brains by immunohistochemistry. We found that, in the brain, NLGN4 is expressed almost exclusively in neurons, in which it has a widespread cytoplasmic pattern of distribution. Among various types of neurons with NLGN4 expression, we identified consistently high expression of NLGN4 in hypothalamic oxytocin (OXT)/vasopressin (AVP)-producing cells. Quantitative analyses revealed that the majority of OXT/AVP-producing neurons expressed NLGN4. NLGN4 signals in other large neurons, such as pyramidal cells in the cerebral cortex and hippocampus as well as neurons in the locus coeruleus and the raphe nucleus, were also remarkable, clearly contrasting with no or scarce signals in Purkinje cells. These data suggest that NLGN4 functions in systems involved in intellectual abilities, social abilities, and sleep and wakefulness, impairments of which are commonly seen in autism.

Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neurons.

OBJECT: The goal of this study was to evaluate the neuroprotective effects conferred by long-term electrical stimulation of the subthalamic nucleus (STN) against degeneration of dopaminergic neurons by assessing motor functional and immunohistological findings in hemiparkinsonian rats. METHODS: In 13 of 25 rats, a concentric microelectrode was stereotactically implanted into the right STN under the guidance of extracellular microelectrode recording. After this had been done the animals were given an injection of 6-hydroxydopamine (6-OHDA) into the right striatum. Seven of the rats received continuous stimulation (frequency 130 Hz, intensity 80-100 microA) for 2 weeks (Group A); the other six did not receive any stimulation during this period (Group B). Twelve rats did not receive electrode implantation and underwent 6-OHDA injection only; these animals served as a control group (Group C). After 2 weeks, motor function in the rats was evaluated by conducting an amphetamine-induced rotation test. Finally, tyrosine hydroxylase-immunoreactive neurons in the pars compacta of the substantia nigra (SNc) were counted to evaluate the extent of degeneration of dopaminergic neurons. Ipsilateral rotation was significantly decreased in Group A, regardless of the effects of stimulation delivered during the test (p < 0.05). Rats in Group B demonstrated typical circling as did those in Group C, except that on stimulation Group B rats immediately stopped circling or changed direction. Tyrosine hydroxylase-immunoreactive neurons in the SNc were significantly preserved in the animals in Group A, whereas neurons in animals in Groups B and C were moderately depleted (p < 0.01). CONCLUSIONS: Acutely, STN stimulation improved rotation symmetry in rats with moderate SNc degeneration. When STN stimulation had been applied for the preceding 2 weeks, motor function was better and SNc neural degeneration was significantly milder. Subthalamic nucleus stimulation thus appears to protect dopaminergic neurons in this hemiparkinsonian model, in addition to improving motor function in these animals.