Effects of adrenal medulla graft on recovery of GABAergic and dopaminergic neuron deficits in mice: behavioural, pharmacological and immunohistochemical study

• Published in: Behavioural brain research Vol. 140; no. 1; pp. 185 - 193
• Main Authors: Jousselin-Hosaja, M., Tobin, C., Venault, P., Joubert, C., Chapouthier, G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 18.03.2003
• Subjects: Adrenal medulla; Adrenal Medulla - physiology; Adrenal Medulla - transplantation; Adrenergic Uptake Inhibitors - pharmacology; Animals; Corpus Striatum - drug effects; Corpus Striatum - injuries; Corpus Striatum - pathology; Dopamine - metabolism; gamma-Aminobutyric Acid - metabolism; Graft; Immunohistochemistry; Locomotion - drug effects; Locomotion - physiology; Male; Membrane Glycoproteins - metabolism; Membrane Transport Proteins; Mice; Motor Activity - drug effects; Motor Activity - physiology; Neurons - metabolism; Neurons - physiology; Neurons - transplantation; Neuropeptides; Neurotoxins - toxicity; Open field; Quinolinic acid; Quinolinic Acid - toxicity; Striatum; Tetrabenazine; Tetrabenazine - pharmacology; Tyrosine 3-Monooxygenase - metabolism; Vesicular Biogenic Amine Transport Proteins; Vesicular Monoamine Transport Proteins; Immunohistochemistry; DA, dopamine; PNMT, phenylethanolamine N-metyltransferase; BSA, bovine serum albumine; QA, quinolinic acid; Adrenal medulla; TBZ, tetrabenazine; Tetrabenazine; VMAT2, vesicular monoamine transporter type 2; Open field; Striatum; GABA, gamma aminobutyric acid; PBS, phosphate-buffered saline; OF, open field; TH, tyrosine hydroxylase; Graft; Mice; Quinolinic acid
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/S0166-4328(02)00315-7

We studied the capacity of adrenal medullary transplant to restore the deficits of GABAergic and dopaminergic neurons in mice injected with quinolinic acid (QA), using an open field test as well as pharmacological and immunohistochemical techniques. We analysed behavioural traits—total locomotor activity, peripheral and central activities, grooming, leaning and rearing in the QA-lesioned mice and mice that had undergone adrenal medulla (AM) transplantation. We found that the adrenal transplant recovered a loss of GABAergic neurons. It reduced QA-induced hyperactivity in locomotion and improved emotional indices. In addition, immunohistochemical studies of catecholaminergic markers—tyrosine hydroxylase (TH), dopamine (DA) and neuronal vesicular monoamine transporter type 2- and a single post-trial injection of tetrabenazine (TBZ; 5 mg/kg) indicated that catecholamines-synthesising chromaffin cells in the AM grafts were also involved in the beneficial effects. A likely interpretation of this behavioural pattern of results is that adrenal medullary transplants set into play an interaction between GABAergic and DAergic factors. Our results may contribute to the clarification of the beneficial effects of AM transplants in striatal function.