Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats.

Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (10(10) pfu) of either an adenoviral vector expressing the gene for beta-galactosidase; (Y-betagal and S-betagal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF, respectively). Transgenic GDNF levels in supernatants of GDNF adenovector-transduced N2a neuronal cell cultures were 25+/-4 ng/ml, as determined by bioassay. In the rats, serum prolactin (PRL) was measured at regular intervals. On day 17 animals were sacrificed and neuronal nuclear antigen (NeuN) and tyrosine hydroxylase (TH) immunoreactive cells counted in the arcuate-periventricular hypothalamic region. The S-GDNF but not the S-betagal rats, showed a significant reduction in body weight. The chronic hyperprolactinemia of the senile females was significantly ameliorated in the S-GDNF rats (P<0.05) but not in the S-betagal rats. Neither age nor GDNF induced significant changes in the number of NeuN and TH neurons. We conclude that transgenic GDNF ameliorates chronic hyperprolactinemia in aging female rats, probably by restoring TIDA neuron function.

Intratentorial osteochondrolipoma in a 9-year-old boy.

Intracranial osteolipomas and chondromas are rare benign tumors. Forty-five chondromas, mostly supratentorial, have been reported in the literature since 1981, with origins most commonly in the sellar regions. Twenty-one osteolipomas have been described to date, usually located near the tuber cinereum or the corpus callosum. The authors present a case of an osteochondrolipoma arising from the tentorium diagnosed in a pediatric patient at the age of 9 years. The case and treatment are discussed, and a review of the literature is provided.

Symptomatic osteolipoma of the tuber cinereum. Case report.

The authors present a case of an ossified lipoma located at the tuber cinereum. Intracranial osteolipomas are rare lesions that occur in the region of the tuber cinereum. Almost all reported cases have been incidental autopsy findings. This report, however, involves a young girl who presented with an ovarian cyst and signs of precocious puberty, in whom a typical osteolipoma was surgically removed. This is the first case of hypothalamic osteolipoma presenting with endocrinological disturbances that has been published to date.

[Reactions of the neurons of various hypothalamic structures to tooth pulp and sciatic nerve A beta-fiber stimulation in the cat]. / Reaktsii neironov razlichnykh struktur gipotalamusa na razdrazhenie pul'py zuba i Abeta-volokon sedalishchnogo nerva u koshki.

Responses of single units from lateral and medial areas of the posterior, tuberal and anterior hypothalamus to electrical stimulation of dental pulp and sciatic nerve A beta afferents were recorded in anesthetized curarized cats. 80.7%, 81.5% and 71.4% of units, respectively, responded to stimulation in posterior tuberal and anterior hypothalamus. The shortest latency of responses was recorded in the postero-lateral hypothalamus. Nociceptive responses in the lateral hypothalamus were of shorter latency than responses of medial hypothalamic units. Marked predominance of excitatory responses in the posterior hypothalamus and almost an equal proportion of excitatory and inhibitory responses in the tuberal and anterior hypothalamus were found. High degree of convergence (85.8%) of noxious and nonnoxious (sciatic nerve A beta afferents) impulses was revealed. Unidirectional, similar pattern of responses of convergent type neurons to stimulation of the tooth pulp and sciatic nerve A beta afferents indicate a nonspecific character of responses of the majority of polysensory neurons. 14.2% of hypothalamic units were monomodal, specific nociceptive neurons. Hypothalamic nociceptive units were characterized by a long recovery cycle (200-500 ms) and low reproducibility of responses to repetitive stimulation of the tooth pulp afferents (1.5-2/s). The neuronal organization of the nociceptive afferent system of the hypothalamus and the functional role of convergent and specific nociceptive neurons of the hypothalamus are discussed.