Amitotic neuroblastoma cells used for neural implants in monkeys.

The potential utility of cultured neuroblastoma cells as donor tissue for neutral implants into the mammalian brain has been examined. Cells from a human neuroblastoma cell line, IMR-32, were labeled with [3H]thymidine and chemically rendered amitotic. These differentiated IMR-32 cells were grafted into the hippocampi of five adult African Green monkeys, and graft survival was evaluated for up to 270 days after transplantation. Autoradiographically labeled grafted cells were identified in four animals. Processes from grafted cells could be followed for distances of up to 150 micrometers into the host brain. No evidence for neoplastic growth of the transplant was found. Thus, grafted neuroblastoma cells can survive for prolonged periods in the primate brain and may serve as a practical source of donor tissue for neural implants.

Cholinergic involvement in osmotic control of vasopressin release by the organ-cultured rat hypothalamo-neurohypophyseal system.

A nicotinic-cholinergic receptor appears to mediate osmotic stimulation of vasopressin (VP) release by the hypothalamo-neurohypophyseal explant. Nicotinic blocking agents, hexamethonium, tetraethylammonium chloride, and trimethaphan, blocked VP release in response to the addition of sufficient NaCl to yield a 10 mosm/kg H2O increase in culture medium osmolality. Atropine at a similar molar concentration was ineffective in blocking VP release in response to the same osmotic stimulus. Tetraethylammonium chloride and trimethaphan also blocked acetylcholine-stimulated VP release. These findings support the hypothesis that the osmoreceptive element responsible for controlling VP release resides in a separate cell and communicates with the VP cell by way of a nicotiniccholinergic receptor.

Role of angiotensin in the osmotic control of vasopressin release by the organ-cultured rat hypothalamo-neurohypophyseal system.

Angiotensin II (AII) appears to either mediate or modulate osmotically stimulated vasopressin (VP) release by the organ-cultured rat hypothalamo-neurohypophyseal system. Saralasin, an AII antagonist, blocked VP release in response to a 10-mosmol increment in culture medium osmolality achieved by the addition of NaCl. This was observed at all concentrations tested (10(-7), 10(-6), 10(-4) M). Saralasin (10(-4) M) also blocked VP release in response to a comparable mannitol-induced increase in osmolality. Since nicotinic-cholinergic antagonists previously were shown to inhibit osmotically stimulated VP release, the effect of hexamthonium, a nicotinic, a nicotinic-cholinergic antagonist, on AII-stimulated VP release was examined. Hexamethonium (10(-5)-10(-3) M) was ineffective in blocking AII stimulation of VP release. This finding coupled with the previous observation that saralasin does not block acetylcholine stimulation of VP release suggests independent AII and cholinergic mechanisms controlling VP release; however, the effectiveness of both types of antagonists in blocking osmotically stimulated VP release indicates some interaction between these regulators of VP release.

Characterization of cholinergic control of vasopressin release by the organ-cultured rat hypothalamo-neurohypophyseal system.

Acetylcholine and nicotine stimulated vasopressin (VP) release from the organ-cultured rat hypothalamo-neurohypophyseal system (HNS). Nicotinic antagonists, hexamethonium, tetraethylammonium chloride, and trimethaphan blocked VP release in response to acetylcholine and nicotine. A muscarinic agonist, methacholine, was ineffective in eliciting VP release from HNS explants at a molar concentration equal to the maximally effective concentration of acetylcholine (10(-5) M). Atropine, a muscarinic antagonist, was an ineffective blocking agent for acetylcholine. These data indicate that the cholinergic receptor in the HNS explant is nicotinic rather than muscarinic in character.

Angiotensin stimulation of vasopressin release from the rat hypothalamo-neurohypophyseal system in organ culture.

Angiotensin II (AII) stimulated vasopressin (VP) release from the rat hypothalamo-neurohypophyseal system (HNS) in organ culture in a concentration-dependent manner. Exposure to AII at 10(-8) M for 1 hr yielded a 1.8-fold increase in VP release over control release (P less than 0.01), while a 1-h exposure to 10(-5) M AII resulted in a 4-fold increment over control VP release by HNS explants maintained in organ culture for 3 days (P less than 0.01). Saralasin, an AII antagonist, blocked AII stimulation of VP release without significantly altering basal VP release by the HNS explants. Saralasin did not interfere with stimulation of VP release by acetylcholine or nicotine. Tetrodotoxin (10(-7) g/ml) also blocked AII stimulation of VP release. These findings suggest that action potentials are generated in response to AII stimulation of specific receptors in the HNS and are requisite for VP release in response to this stimulus.

The long-term effects of callosal sectioning. Report of a second case.

Testing a patient 32 years after callosal sectioning revealed defects in transfer of learning and crossed (mixed modality) matching. This points out that defects may persist long after such surgery and that early reports of negative results of callosal section in patients were probably not correct.

Neuropeptides in aging and dementia.

Although senile dementia of the Alzheimer's type (SDAT) is a common disease associated with advancing age, recent studies have suggested that SDAT should not be considered synonymous with old age but a disease process separate from normal aging. This study examined the morphology of two neurochemically-defined neuronal populations (i.e., neurophysin, somatostatin) in the cortex and hypothalamus to determine if structural changes in these neuropeptide systems associated with advancing age are similar to those seen with SDAT. Our findings suggest that morphological changes consistent with neuronal degeneration occur in somatostatin but not neurophysin-containing neurons in cases diagnosed to have SDAT, and these structural changes are different from those seen in aged brain without central nervous system disease. These data support the concept that senile dementia of the Alzheimer's type is not a single neurochemical related disease, but may be associated with anatomical lesions and biochemical imbalances among a number of neuropeptide and neurotransmitter systems.