A single cell clonal line which responds reversibly to nerve growth factor (NGF) has been established from a transplantable rat adrenal pheochromocytoma. This line, designated PC12, has a homogeneous and near-diploid chromosome number of 40. By 1 week's exposure to NGF, PC12 cells cease to multiply and begin to extend branching varicose processes similar to those produced by sympathetic neurons in primary cell culture. By several weeks of exposure to NGF, the PC12 processes reach 500-1000 mum in length. Removal of NGF is followed by degeneration of processes within 24 hr and by resumption of cell multiplication within 72 hr. PC12 cells grown with or without NGF contain dense core chromaffin-like granules up to 350 nm in diameter. The NGF-treated cells also contain small vesicles which accumulate in process varicosities and endings. PC12 cells synthesize and store the catecholamine neurotransmitters dopamine and norepinephrine. The levels (per mg of protein) of catecholamines and of the their synthetic enzymes in PC12 cells are comparable to or higher than those found in rat adrenals. NGF-treatment of PC12 cells results in no change in the levels of catecholamines or of their synthetic enzymes when expressed on a per cell basis, but does result in a 4- to 6-fold decrease in levels when expressed on a per mg of protein basis. PC12 cells do not synthesize epinephrine and cannot be induced to do so by treatment with dexamethasone. The PC12 cell line should be a useful model system for neurobiological and neurochemical studies.

https://www.pnas.org/content/pnas/73/7/2424.full.pdf

Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.

https://www.cell.com/cell/pdf/S0092-8674(00)80949-6.pdf

Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

Parkinson's disease: Mechanisms and models

Primate models of movement disorders of basal ganglia origin

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.

/pdf/the-hypocretins-hypothalamus-specific-peptides-with-4pipr77drn.pdf

The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

Defective myelin lipid synthesis as a pathogenic mechanism of Canavan disease.

Catecholamine concentration of discrete brain areas following self-stimulation in the ventromedial tegmentum of the rat.

Adrenergic fibers from the iris enter and reinnervate segments of ovarian autografts transplanted to the anterior chamber of the cat eye. The distribution of adrenergic fibers is similar to that found in the intact ovary. Therefore, ovarian transplants are not to be considered as isolated from sympathetic innervation. Endocrinology 86: 921, 1970)

David M. Jacobowitz

Papers

Defective myelin lipid synthesis as a pathogenic mechanism of Canavan disease.

Catecholamine concentration of discrete brain areas following self-stimulation in the ventromedial tegmentum of the rat.

Adrenergic Reinnervation of the Cat Ovary Transplanted to the Anterior Chamber of the Eye

Effect of hypophysectomy on α-melanotropin in discrete regions of the rat brain

Catecholamines and vasopressin in forebrain nuclei of hypertension prone and resistant rats.